Biofiles Volume 7, Number 5

Pharmaceutical Drugs and Drug CandidatesAntihypertensive Agents

Antilipemic Agents

Anticoagulants

Biofilescontents

Introduction 3

Antihypertensive Agents 5

Angiotensin-Converting Enzyme (ACE) Inhibitors 5

Angiotensin II Receptor Blockers (ARBs) 8

α1-Adrenoreceptor Blockers 11

β-Adrenergic Blockers 14

Calcium Channel Blockers (CCBs) 16

Diuretics 19

Antilipemic Agents 21

3-Hydroxy-3-Methylglutaryl Coenzyme A (HMG-CoA) Reductase Inhibitors 21

Peroxisome Proliferator-Activated Receptor (PPAR) Agonists 23

Acyl–Coenzyme A:Cholesterol Acyltransferase (ACAT) Inhibitors 24

Anticoagulants 25

Cover: Advances in pharmacology offer new approved therapeutics and drug candidates for the treatment of hypertension.

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Highlights in this issue: Scientists look to Sigma® Life Science

as a trusted source for small molecules to use as research tools in their effort to

unravel the mystery of disease. In the following pages, we will not only present

the approved therapeutics and drug candidates to advance hypertension

research, but also some complementary products such as antibodies, zinc finger nucleases, and more.

By providing you with best-in-class products across multiple stages of your research, you can focus more on what matters most:

the new idea that will lead to the next breakthrough.

Upcoming issue:The next issue of Biofiles will feature dietary

bioactives, specifically phytochemicals and functional foods studied for their added

health and physiological benefits that extend beyond normal nutritional value.

Their antioxidant, anti-proliferative and anti-inflammatory activities contribute

to health maintenance and disease prevention, making them optimal targets for pharmaceutical

alternatives and novel nutraceuticals.

Technical content: Sami BarghshoonProduct Manager – Bioactive Small Moleculessami.barghshoon@sial.com

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IntroductionSami BarghshoonProduct Manager – Bioactive Small Moleculessami.barghshoon@sial.com

The development of effective medications has led to progress in controlling both blood pressure and cholesterol level.1-2 Antihypertensive and antilipemic agents have vastly improved the treatments available for hypertension and the quality of life of individuals with this condition.

In 2011, there were 299 drug candidates under development and 5,701 clinical trials (Open Studies only) worldwide.3-4 From this group, 27 drug candidates are under evaluation for hypertension in 664 clinical trials and 43 candidates in 103 clinical trials for lipid disorders.

The majority of hypertension clinical trials focus on combination therapies while lipid disorders examine the combination of lifestyle and medication intervention on managing the disease.

Much of the groundwork for approved therapeutics and drug candidates under development came from extensive basic research in hypertension.5 Researchers are continually working to discover new ways to approach the R&D process; researchers must creatively tackle unforeseen challenges and thoroughly collect data on all aspects of the drug’s safety and efficacy.

Sigma® Life Science is currently collaborating with Pfizer to provide you access to several of their approved therapeutics and drug candidates for your research efforts. Our bioactive small molecules portfolio also extends to include compounds from GSK, Merck, AstraZeneca, and more.

We work closely with academic and government institutions. Along with your peers from the Broad Institute and Northeastern University, we select compounds to provide you with the latest and most relevant research tools for evaluating drug targets for the study of hypertension.

By ensuring a comprehensive portfolio, we make it easier for you to find the needed approved therapeutics and drug candidates for cardiovascular research. That means your flashes of inspiration and persistent dedication might lead to new treatments for hypertension sooner than you expected.

This Biofiles issue concentrates on our selection of approved therapeutics and drug candidates for hypertension. Our portfolio includes antihypertensive agents such as:

•Angiotensin converting enzyme inhibitors

•Angiotensin receptor blockers

•β-adrenoreceptor blockers

•Calcium channel blockers

•Thiazide diuretics

We also explore antilipemic—HMG-CoA reductase and ACAT inhibitors—and anticoagulant agents. Complementary products such as antibodies, peptides, biomolecules (naturally-derived compounds), and zinc finger nucleases are included.

4

And we don’t offer a “one size fits all.” Sigma® Life Science offers a host of products and services to support your research, including our Library of Pharmacologically Active Compounds LOPAC®, knockout rat models from SAGE® laboratories, and MISSION® ID Library for gene target identification. We aim to provide elegant solutions that are tailored to your specific research needs.

Basic and clinical research continue to make remarkable progress in understanding cardiovascular biology. At the heart of this progress is our commitment to provide you with the best tools to do your best work in advancing the promise of science.

References1. Roger et al. 2011. Heart disease and stroke

statistics-2011 update: A report from the American Heart Association. Circulation 123:e18-e209.

2. Arima, H. and Chalmers, J. 2011. PROGRESS: Prevention of recurrent stroke. J Clin Hypertens 13:693-702.

3. PhRMA. 2011. Medicines in development for heart disease and stroke. http://www.phrma.org/sites/default/files/422/heart2011.pdf

4. NIH. 2011. Clinical Trials: Open studies in cardiovascular disease. http://www.clinicaltrials.gov

5. PhRMA. 2011. Pharmaceutical industry profile. http://www.phrma.org/sites/default/files/159/phrma_profile_2011_final.pdf

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Antihypertensive Agents

Antihypertensive AgentsACE InhibitorsAgents that inhibit angiontensin-converting enzymes (ACE) and angiotensin II formation are essential to cardiovascular medicine.1 These inhibitors are used not only to treat essential hypertension and complications associated with it, but also to prevent cardiovascular, cerebrovascular, and renal complications.2,3

The first oral ACE inhibitor therapeutic was developed in the 1970s,4 and was soon followed by other ACE inhibitors with more attractive pharmacodynamic effects.

Millions of people use ACE inhibitors on a daily basis to manage hypertension. In the U.S., roughly 163 million prescriptions were filled in 2009, making this class of therapeutics the country’s fourth most widely prescribed medicine.5

The U.S. Food and Drug Administration (FDA) has approved 10 ACE inhibitors for the treatment of hypertension and there are 15 ACE inhibitors approved worldwide.

Sigma® Life Science offers you all 15 approved ACE inhibitors at competitive prices. We strive to provide you with the highest quality of approved therapeutics available. Look no further than Sigma® Life Science for precision and control over your research experiments.

For more information and a complete list of small molecules and related products, visit sigma.com/therapeutics.

References1. Gradman et al. 2010. American society of hypertension

writing group. Combination therapy in hypertension. J Am Soc Hyperten 4:42–50.

2. Ferguson et al. 1977. A specific orally active inhibitor of angiotensin-converting enzyme in man. Lancet 1:775–8.

3. Re, RN. 2001. The clinical implication of tissue renin angiotensin systems. Curr Opin Cardiol 16:317–327.

4. Ondetti et al. 1977. Design of specific inhibitors of angiotensin-converting enzyme: new class of orally active antihypertensive agents. Science 196:441–4.

5. Consumer Reports. 2011. Using ACE Inhibitors to treat high blood pressure and heart disease. http://consumerreportshealth.org

ACE Inhibitors – Approved Therapeutics

Name Structure CAS No. Cat. No.

CaptoprilN

O

OH

OHS

CH3

62571-86-2 C4042-5GC4042-25G

Edrophonium chlorideN

CH3H3COHH3C

Cl

116-38-1 E3256-250MGE3256-1G

Enalapril maleate salt

NH

O

N

OH

O

HO

O

COOH

CO2CH2CH3 76095-16-4 E6888-250MGE6888-1GE6888-5G

Enalaprilat dihydrate

NH

OHOCH3

N

O

OH

O

• 2H2O

84680-54-6 E9658-5MGE9658-25MG

Fosinopril sodium

NONa

OOP

O

O OCH3

Oi-Pr

88889-14-9 F1308-5MGF1308-25MG

6

Name Structure CAS No. Cat. No.

Imidapril hydrochloride

N O

CH3

HO

HN

O CH3

OO

CH3

N

O

• HCl

89396-94-1 SML0148-10MGSML0148-50MG

Itopride hydrochlorideH3CO

H3CO

NH

O

ON

CH3

CH3

• HCl122892-31-3 SML0033-10MG

SML0033-50MG

Lisinopril

NH

O

N

O OHO

NH2

OH

• 2H2O

83915-83-7 L6292-100MGL6292-250MG

Moexipril hydrochloride

(S)(S)

NH

O

OH3C

(S)(S)

H3C

ON(S)(S)

H3CO

H3CO

O

OH

• HCl

82586-52-5 M0821-50MGM0821-100MG

Perindopril erbumine

NOH

O

O

HN

O CH3

CH3

O

CH3

H

H

CH3

CH3

H3C NH2•

107133-36-8 P0094-50MGP0094-250MG

Pyridostigmine bromide

NCH3

O NCH3

O

CH3

Br

101-26-8 P9797-1GP9797-5G

Quinapril hydrochloride

N

O

OH• HCl

HN

OO CH3

OH3C

82586-55-8 Q0632-250MGQ0632-500MG

Ramipril

NH

C2H5OOCN

O

CH3

HOOC

H

H87333-19-5 R0404-100MG

R0404-250MG

Trandolapril

N

H

H

OH

O

O

HN

O CH3

CH3

O

Ph

87679-37-6 T4827-10MGT4827-50MG

Zofenopril calcium

N

SPh

O

OO

CH3

S

O

2

Ca2+

81938-43-4 Z1252-5MGZ1252-25MG

ACE Inhibitors – Approved Therapeutics (continued)

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Angiontensin converting enzyme (ACE) inhibitors are not the only products available at Sigma® Life Science for this target class. You can also find antibodies, biomolecules, peptides, and zinc finger nucleases. We offer you more resources so you can spend less time looking for products and more time on your research.

Antibodies to ACE

Product Name Host Clone No. Form Gene Symbol Species Reactivity Application Prestige Antibody Cat. No.

Anti-ACE rabbit - affinity isolated antibody ACE, human human IHC (p)PA

✔ HPA029298-100UL

Monoclonal Anti-ACE mouse 6A4 purified immunoglobulin ACE, human human ELISA (i)WB

- WH0001636M1-100UG

Monoclonal Anti-ACE mouse 4B10 purified immunoglobulin ACE, human human ELISA (c)ELISA (i)WB

- SAB1403725-100UG

Biochemicals for ACE Research

Name Structure CAS No. Cat. No.

(Z)-Guggulsterone

O

O

CH3

H3C

H3C

H H

H

39025-23-5 G5168-5MGG5168-25MG

(−)-Huperzine A

HNO

NH2

H3C

H3C

H

102518-79-6 H5902-1MG

Quinine hemisulfate salt monohydrate

N

N

H2C

HO

H3CO

2

• H2SO4

• 2H2O

207671-44-1 Q1250-5GQ1250-10GQ1250-50G

(±)-Synephrine - 94-07-5 S0752-5G

Theobromine

N

HN

N

N

O

O

CH3

CH3 83-67-0 T4500-25GT4500-100G

Proteins and Peptides for ACE Research

Product Name Gene Symbol Purity CAS No. Cat. No.

Abz-LFK(Dnp)-OH trifluoroacetate salt - ≥98%, HPLC - A5855-1MG

Angiotensin Converting Enzyme from rabbit lung ACE - 9015-82-1 A6778-.1UNA6778-.25UNA6778-1UNA6778-2UNA6778-5UN

Angiotensin Converting Enzyme Inhibitor - ≥95%, TLC 35115-60-7 A0773-1MGA0773-5MG

Angiotensin I human acetate salt hydrate AGT ≥90%, HPLC 70937-97-2 A9650-1MGA9650-5MGA9650-10MGA9650-50MG

Angiotensin II human AGT ≥93%, HPLC 4474-91-3 A9525-1MGA9525-5X1MGA9525-5MGA9525-10MGA9525-50MG

8

Product Name Gene Symbol Purity CAS No. Cat. No.

N-[3-(2-Furyl)acryloyl]-Phe-Gly-Gly ACEACE2ACE3

- 64967-39-1 F7131-25MGF7131-100MGF7131-500MG

Hippuryl-His-Leu acetate salt ACEACE2ACE3

- 103404-54-2 H4884-25MGH4884-100MGH4884-500MGH4884-1G

N-Hippuryl-His-Leu hydrate ACEACE2ACE3

≥98%, HPLC 207386-83-2 H1635-25MGH1635-100MGH1635-500MGH1635-1G

Zinc Finger Nucleases for ACE Research

Name Gene Symbol Cat. No.

CompoZr® Knockout ZFN Kit ACE CKOZFN1813-1KT

CompoZr® Knockout ZFN Kit, ZFN plasmid only Ace CKOZFND26143-1KT

CompoZr® Knockout ZFN Kit, ZFN plasmid only ACE CKOZFND1813-1KT

ARBsHypertension can result from excessive activity of the renin-angiotensin-aldosterone system (RAAS) and this overactivity can injure critical organs such as the heart and blood vessels.1

In the 1990s, angiotensin II receptor blockers (ARBs) became commercially available to block the activity of RAAS.2

Unlike ACE inhibitors which prevent angiotensin I conversion to II, ARBs bind to the angiotensin II AT1 receptor, blocking the cellular actions triggered by angiotension II.3

Over the past two decades, studies in the laboratory and clinic have documented that ARBs, either alone or in combination with thiazide-type diuretics, reduce blood pressure in animals and humans.4

The pharmacological differences among ARBs are how they exert their effects. Some ARBs compete with angiotensin II in a concentration-dependent manner for AT1 receptor binding while others irreversibly bind to the receptor.5

At Sigma® Life Science, you will find six approved therapeutics in this target class. We strive to provide you with a comprehensive selection of approved therapeutics so you don’t have to spend a lot of time and effort to find them.

Visit sigma.com/therapeutics for a listing of all approved drugs and drug candidates.

References1. Savoia C, Schiffrin EL. 2007. Vascular inflammation in

hypertension and diabetes: molecular mechanisms and therapeutic interventions. Clin Sci 112:375–384.

2. Ferrario, CM. 2006. Role of angiotensin II in cardiovas-cular disease therapeutic implications of more than a century of research. J Renin Angiotensin Aldosterone Syst 7:3–14.

3. Oparil, S. 2000. Newly emerging pharmacologic differences in angiotensin II receptor blockers. Am J Hypertens 13:18S–24S.

4. Addison et al. 2011. Angiotensin receptor blockers: Pharmacology, efficacy, and safety. J Clin Hypertens 13:677–86.

5. Munger, MA. 2011. Use of angiotensin receptor block-ers in cardiovascular protection: current evidence and future directions. Pharmacy & Therapeutics 36:22-40.

Proteins and Peptides for ACE Research (continued)

Order sigma.com/order Technical service sigma.com/techinfo sigma.com/lifescience 9

ARBs - Approved Therapeutics

Name Structure CAS No. Cat. No.

Candesartan cilexetil

N

N

OO

O

O

CH3

NNN

NH

O

O

H3C 145040-37-5 SML0245-10MGSML0245-50MG

Eprosartan mesylate

N

N

O

OH

H3C OH

O

SH3C S

O

OOH•

144143-96-4 E2535-10MGE2535-50MG

IrbesartanN

NO CH3

NN

NNH

138402-11-6 I2286-10MGI2286-50MG

Losartan potassium

N

NCl

HO

KN NN

N

CH3

124750-99-8 61188-100MG

Telmisartan

N

N

CH3

CH3

N

NCH3

O OH

144701-48-4 T8949-10MGT8949-50MG

Valsartan

H3C

O NOH

O

H3C

HN N

NN

CH3

137862-53-4 SML0142-10MGSML0142-50MG

In addition to angiotensin II receptor blockers (ARBs), Sigma® Life Science also offers antibodies, peptides, and zinc finger nucleases for this target class. At sigma.com, you can search our collection and obtain more information about any of our products.

Antibodies to Angiotensin II Receptor Type 1 (AGTR1)

Product Name Host Form Gene Symbol Species Reactivity Application Prestige Antibody Cat. No.

Anti-AGTR1 rabbit affinity isolated antibody AGTR1, human human IHC (p)PA

✔ HPA003596-100UL

Anti-AGTR1 rabbit affinity isolated antibody AGTR1, human humanmouserat

ELISA (i)IHCWB

- SAB3500209-100UG

Anti-AGTR1 rabbit affinity isolated antibody AGTR1, human bovinecaninehuman, mouse, ratpigrabbit

WB - SAB2100073-50UG

Anti-AGTR1/AT1 goat affinity isolated antibody AGTR1, human humanmouserat

ELISA (i)WB

- SAB2500038-100UG

10

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Alpha (α) Blockersα1-Antagonists (α-blockers) selectively block post-synaptic α1-adrenoreceptors and prevent catecholamine-induced constriction of arteries and venous vascular beds, thereby lowering blood pressure.1

However, α-blockers administered over time increase an individual's extracellular fluid and plasma volumes.2 This expansion typically manifests as weight gain and an attenuation of blood pressure. Therefore, these therapeutics are contraindicated in persons with heart failure because of their ability to expand extracellular and plasma volumes.3

One therapeutic strategy to counter the induced expansion is the administration of α1-adrenoreceptor antagonists with diuretics such as chlorthalidone or hydrochlorothiazide.4 The diurectics mitigate the expansion of the extracellular and plasma volumes, providing significant incremental reductions in blood pressure. Diuretics available from Sigma® Life Science are discussed in a subsequent section.

Sigma Life Science is your definitive source for all approved α-blockers that are available at competitive prices. This includes the first generation of nonselective α-receptor antagonists,

phentolamine and phenoxybenzamine, as well as the quinazoline-selective α1-adrenoreceptor blockers.

Visit sigma.com/therapeutics for a listing of approved drugs and drug candidates.

References1. Neaton et al. 1993. Treatment of mild hypertension

study. JAMA 270:713–24.2. Wright et al. 2008. Clinical outcomes by race in hyper-

tensive patients with and without metabolic syndrome. Arch Intern Med 168:207–17.

3. David et al. 2008. Heart failure with preserved and reduced left ventricular ejection fraction in antihyper-tensive and lipid-lowering treatment to prevent heart attack trial. Circulation 118:225E–67E.

4. Barzillay et al. 2004. Cardiovascular outcomes using doxazosin vs chlorthalidone for the treatment of hypertension in older adults with and without glucose disorders. J Clin Hypertens 6:116–25.

α-Blockers – Approved Therapeutics

Name Structure CAS No. Cat. No.

Alfuzosin hydrochloride

N

N

N NH

O

NH2

H3CO

H3CO

O

CH3

• HCl81403-68-1 A0232-5MG

A0232-25MG

Doxazosin mesylate

N

N

NH2

H3CO

H3CO NN

OO

O

SO

OOHH3C•

77883-43-3 D9815-50MGD9815-250MG

Fiduxosin hydrochloride O

N

N

HN S

N N

O

H

H

OO

• HCl

- F4303-5MGF4303-25MG

Naftopidil hydrochloride hydrate

N

NOCH3

OHO

• HCl• xH2O

- N158-25MGN158-100MG

Phenoxybenzamine hydrochloride

NO

CH3

• HCl

Cl

63-92-3 B019-250MG

12

Name Structure CAS No. Cat. No.

Phentolamine hydrochloride CH3

N OHN

NH

HCl

73-05-2 P7547-100MGP7547-500MG

Prazosin hydrochloride

N

N

NH2

H3CO

H3CO NN

OO

• HCl

19237-84-4 P7791-50MGP7791-250MGP7791-1G

Terazosin hydrochloride

N

NH3CO

H3CO

NH2

NN

OO

• HCl

63590-64-7 T4680-50MGT4680-250MG

Urapidil hydrochlorideN

OCH3

N CH2CH2CH2 N

N

NHO

OCH3

CH3

• HCl

64887-14-5 U100-100MGU100-500MG

α-Blocker Drug Candidates

Name Structure CAS No. Cat. No.

A-315456 N

NH

NH

SO

O

CH3

- A6351-5MGA6351-25MG

L-765,314 hydrate

N

N

NH2

H3CO

H3CO NN O

O

NH

t-BuO

• xH2O - L3040-5MGL3040-25MG

α-Blockers – Approved Therapeutics (continued)

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Sigma® Life Science also offers antibodies, biomolecules, and zinc finger nucleases for the study of α1-adrenoreceptors. With more resources, you can spend less time looking for products and more time on your research.

Visit sigma.com to search through our extensive product portfolio of antihypertensive agents.

Antibodies to α-Adrenergic Receptor Proteins (ADRA1A)

Product Name Host Clone No. Form Gene SymbolSpeciesReactivity Application

Prestige Antibody Cat. No.

Anti-ADRA1A rabbit - affinity isolated antibody ADRA1A, human humanmouserat

ELISA (i)IF (i)

- SAB4500530-100UG

Anti-ADRA1A rabbit - affinity isolated antibody ADRA1A, human human IHC (p)PA

✔ HPA029678-100UL

Monoclonal Anti-ADRA1A mouse 4C7 purified immunoglobulin ADRA1A, human human ELISA (i)WB

- WH0000148M1-100UG

Anti-ADRA1A, C-Terminal rabbit - affinity isolated antibody ADRA1A, human human ELISA (i)WB

- SAB4500529-100UG

Monoclonal Anti-ADRA1A, (N-terminal)

mouse 5G8 purified immunoglobulin ADRA1A, human human ELISA (i)WB

- SAB1403528-100UG

Anti-α1 Adrenergic Receptor rabbit - affinity isolated antibody Adra1d, mouseADRA1B, humanADRA1D, humanAdra1d, ratADRA1A, human

humanmouserat

IF (i)WB

- A270-100UL

Anti-α1C Adrenergic Receptor rabbit - affinity isolated antibody ADRA1A, human human IHC (p) - A4604-50UL

Biochemicals for α1-Adrenoreceptor Research

Name Structure CAS No. Cat. No.

Benoxathian hydrochloride

O

SHN

O

H3CO

OCH3• HCl

92642-97-2 B016-10MGB016-25MG

(±)-Octopamine hydrochloride

HCl

NH2

HO

OH

770-05-8 O0250-1GO0250-5GO0250-10G

Zinc Finger Nucleases for α1-Adrenoreceptor Research

Name Gene Symbol Cat. No.

CompoZr® Knockout ZFN Kit ADRA1A CKOZFN2898-1KT

CompoZr® Knockout ZFN Kit, ZFN plasmid only Adra1a CKOZFND26353-1KT

CompoZr® Knockout ZFN Kit, ZFN plasmid only Adra1a CKOZFND50299-1KT

CompoZr® Knockout ZFN Kit, ZFN plasmid only ADRA1A CKOZFND2898-1KT

14

Beta (β) BlockersThe first β-adrenergic blockers (β-blockers) were identified as antihypertensive agents in the early 1960s.1,2 The first approved drug, propranolol, was used as an adjunct therapy to phentolamine in the treatment of pheochromocytoma.3,4

In the U.S. and Europe, β-blockers are recommended as a first-line treatment for hypertension. This recommendation is based on reduced mortality and morbidity in large clinical trials. Most of the benefit from β-blockers stems from secondary vascular protection in established disease instead of primary prevention.5

There is no consensus regarding how β-blockers lower blood pressure and it is probable that several mechanisms are at work. Mechanisms to account for the antihypertensive actions of β-blockers include reduction in peripheral vascular resistance and inhibition of renin release.3

β-blockers are not uniform in their various pharmacologic effects. Some of the differences between β-blockers include sympathomimetic and membrane-stabilizing activities, β1 selectivity, α1-adrenergic-blocking, solubility in tissue, routes of systemic elimination, potencies, and duration of action.6 This variation contrasts with other classes of antihypertensive drugs and may be important in the selection of a drug for clinical or research use.

β-blockers are taken by tens of millions of Americans everyday. In 2009, these therapeutics were the fifth most widely prescribed class of medicines in the United States with 128 million prescriptions filled.7

To date, the Food and Drug Administration (FDA) has approved 15 β-blockers for oral use in patients with systemic hypertension. Sigma® Life Science is your only source for all 15 approved β-blockers. You’re more likely to find the β-blockers for your research needs at Sigma Life Science than anywhere else.

For a complete listing of all approved drugs and drug candidates, visit sigma.com/therapeutics.

References1. Prichard BNC.1964. Hypotensive action of pronethalol.

Br Med J 1:1227–8.2. Prichard BNC, and Gillam PMS. 1964. Use of propranolol

(Inderal) in the treatment of hypertension. Br Med J 2:725–7.

3. Frishman WH. 2011. α- and β-adrenergic blocking drugs. In: Frishman WH, Sica DA (eds.). Cardiovascular Pharmacotherapeutics, 3rd ed. Minneapolis, MN: Cardiotext Inc. Pg 57–86.

4. Frishman WH, Sica DA. 2008. β-Adrenergic blockers. In: Izzo JL Jr, Sica D, Black HR (eds.). Hypertension Primer, 4th ed. The Essentials of High Blood Pressure. Philadel-phia, PA: Wolters Kluwer Lippincott Williams & Wilkins Pg 446–50.

5. Chobanian et al. 2003. The Seventh report of the joint national committee on prevention, detection, evalua-tion and treatment of high blood pressure: the JNC-7 report. JAMA 289:2560–72.

6. Frishman WH. 2008. β-Adrenergic blockers: a 50-year historical perspective. Am J Ther 15:565–76.

7. Consumer Reports. 2011. Using β-blockers to treat high blood pressure and heart disease. http://consumerre-portshealth.org

β-Blockers – Approved Therapeutics

Name Structure CAS No. Cat. No.

Acebutolol hydrochloride

O

CH3

O

OHHN

CH3

CH3

NH

O

H3C

• HCl

34381-68-5 A3669-1G

AtenololO

HN CH3

CH3

OH

H2N

O

29122-68-7 A7655-1GA7655-5GA7655-25G

Betaxolol hydrochloride

O

OHN CH3

OH

CH3• HCl

63659-19-8 B5683-10MGB5683-50MG

Bisoprolol hemifumarate saltO

O CH3

CH3ONH

H3C

CH3

OH

OHHO

O

O• ½

104344-23-2 B2185-10MGB2185-50MG

Carvedilol

NH

OOH

NH

O

H3CO

72956-09-3 C3993-50MGC3993-250MG

Esmolol hydrochloride

OCH3

O

ONH

OHH3C

CH3

• HCl

81161-17-3 E8031-10MGE8031-50MG

Order sigma.com/order Technical service sigma.com/techinfo sigma.com/lifescience 15

Name Structure CAS No. Cat. No.

Labetalol hydrochloride

HO

NH2O

HN

OH

CH3

• HCl

32780-64-6 L1011-5GL1011-10G

(±)-Metoprolol (+)-tartrate saltO HO

OHO

OOH

OHH3CO

HN CH3

CH3

OH

• ½

56392-17-7 M5391-1GM5391-5GM5391-10G

Nadolol OH

OHO

HN CH3

CH3

CH3

HO

42200-33-9 N1892-1GN1892-5G

Nebivolol hydrochloride

O

F

NH

O

F

OHOHH

H • HCl

152520-56-4 N1915-10MGN1915-50MG

Penbutolol hydrochloride

O NH

OH

• HCl

t-Bu

28163-36-2 32838-10MG

Pindolol

NH

O

HN CH3

OH

CH3

13523-86-9 P0778-250MGP0778-1G

(±)-Propranolol hydrochloride

O NH

CH3

OH

CH3

• HCl

318-98-9 P0884-1GP0884-5GP0884-25GP0884-100G

(±)-Sotalol hydrochloride

NH

SH3C

O

O

HN CH3

CH3

OH

• HCl

959-24-0 S0278-25MGS0278-100MG

Timolol maleate salt

NS

N

NO

OHN CH3

CH3

CH3

OH

• OHHO

O O

H H

26921-17-5 T6394-100MGT6394-250MGT6394-1G

β-Blockers – Approved Therapeutics (continued)

16

In addition to β-blockers, Sigma® Life Science also offers antibodies that target the β-adrenergic receptors. Visit sigma.com to search our entire portfolio and obtain more information about any of our products.

Antibodies to Adrenergic β-1-Receptor Proteins (ADRB1)

Product Name Host Form Gene Symbol Species Reactivity Application Prestige Antibody Cat. No.

Anti-ADRB1 goat affinity isolated antibody ADRB1, human caninehumanmouserat

ELISA (i)WB

- SAB2500034-100UG

Anti-ADRB1 rabbit affinity isolated antibody ADRB1, human humanmouserat

ELISA (i)WB

- SAB4500573-100UG

Anti-ADRB1 rabbit affinity isolated antibody ADRB1, human caninehuman, mouse, ratpig

WB - SAB2100064-50UG

CCBsCalcium channel blockers (CCBs) inhibit the movement of extracellular calcium across the cell membrane through ion-specific channels. Although several types of channels exist, CCBs target the L-type channels in humans. Inhibition of the inward calcium flux causes smooth vascular muscle cell relaxation, resulting in vasodilation and lowering of blood pressure.1

There are two groups of approved therapeutics that target L-type calcium channels, dihydropyridine and nondihydropyridine compounds. The two types bind to different sites on the channel.2 However, nondihydropyridine calcium channel blockers differ from the dihydropyridine subclass in that they are more negatively chronotropic and inotropic. This difference is important for patients who also require β-blockers to manage their hypertension.

One aspect of CCBs that differentiate them from other antihypertensive agents is their ability to reduce blood pressure across all patient groups, regardless of sex, race/ethnicity, age, and dietary sodium intake.3

Currently, there are eight dihydropyridine and two nondihydropyridine approved therapeutics. These therapeutics are for individual use or in combination with other antihypertensive drugs, including statins.3

In 2009, CCBs were the ninth most widely prescribed class of medicines in the United States with 92 million prescriptions. CCBs not only help people manage their high blood pressure, angina, and certain heart rhythm abnormalities, they can also be used to treat migraines, poor circulation to the hands and feet, and certain psychiatric disorders.4

Sigma Life Science currently offers all the dihydropyridine approved therapeutics except for clevidipine, which is not available for research purposes. The two nondihydropyridine approved therapeutics, diltiazem (Cat. No. D2521) and verapamil (Cat. No. V4629), can also be obtained from Sigma Life Science.

There are other approved CCBs that are useful tools in hypertension research. These research therapeutics are listed below and include the two drug candidates azelnidipine (Cat. No. A7106) and cilnidipine (Cat. No. C1493).

At Sigma, we strive to provide you with the largest selection of approved therapeutics available. You’re more likely to find the CCBs for your research needs at sigma.com/therapeutics than anywhere else.

References1. Abernethy DR and Schwartz JB. 1999. Calcium-antagonist

drugs. N Engl J Med 341:1447-57.2. Materson BJ. 1995. Calcium channel blockers: is it

time to split the lump? Am J Hypertens 8:325-9.3. Elliott et al. 2011. Calcium channel blockers. J Clin

Hypertens 13:687-9.4. Consumer Reports. 2011. Using calcium channel

blockers to treat high blood pressure and heart disease. http://consumerreportshealth.org

Order sigma.com/order Technical service sigma.com/techinfo sigma.com/lifescience 17

CCBs – Approved Therapeutics

Name Structure CAS No. Cat. No.

Amlodipine besylate

NH

H3CO

NH2

Cl

• C6H5SO3H

O

H3CO O

O

CH3

111470-99-6 A5605-10MGA5605-50MG

(+)-cis-Diltiazem hydrochloride

N

S

OO C CH3

OCH3

N

CH3

CH2CH2

OCH3

HCl

H

H

33286-22-5 D2521-1GD2521-5GD2521-10G

Dronedarone hydrochloride

O

HNSH3C

O

O • HCl

O

O N CH3

CH3

CH3

141625-93-6 D9696-10MGD9696-50MG

Felodipine

NH

CH3H3C

OH3C

O CH3

O OCl

Cl 72509-76-3 F9677-5MGF9677-25MG

Flavoxate hydrochlorideN

O O

O

OCH3

• HCl

3717-88-2 F8304-10MGF8304-50MG

Ibutilide hemifumarate saltSO

OCH3

HN

NCH3(CH2)5CH2

CH3OH

HOOH

O

O

• ½

122647-32-9 I9910-10MGI9910-50MG

Isradipine

NH

H3C CH3

O

O CH3

CH3H3CO

ON

ON 75695-93-1 I6658-5MG

I6658-25MG

Mibefradil dihydrochloride hydrate

NH

NNCH3

O

H3C CH3

OH3CO F

• 2HCl • xH2O

- M5441-5MGM5441-25MG

Nicardipine hydrochloride

NH

H3C CH3

O

H3CO

NO2

O

O

• HCl

NCH3

54527-84-3 N7510-1GN7510-5GN7510-10G

Nifedipine

NH

NO2

CO

CH3O C

O

OCH3

CH3 CH3

21829-25-4 N7634-1GN7634-5GN7634-10GN7634-25G

18

Name Structure CAS No. Cat. No.

Nimodipine

NH

NO2

O

O

O

OOCH3H3C

CH3

CH3H3C

66085-59-4 N149-100MGN149-500MG

Nisoldipine

NH

OCH3

O

CH3H3C

OH3C

O

CH3

NO2

63675-72-9 N0165-10MGN0165-50MG

(±)-Verapamil hydrochloride

N

OCH3

H3CO

CNCH3

H3C CH3

OCH3

OCH3• HCl

152-11-4 V4629-1GV4629-5GV4629-10G

CCB Drug Candidates

Name Structure CAS No. Cat. No.

Azelnidipine

NH

NH2H3C

OH3C

CH3

O

N

NO2

O O

123524-52-7 A7106-10MGA7106-50MG

Cilnidipine

NH

NO2

H3C CH3

O OH3CO

O O

H

H

132203-70-4 C1493-10MGC1493-50MG

Calcium channel blockers (CCBs) are not the only products available at Sigma® Life Science for this target class. We also provide antibodies, biomolecules, and zinc finger nucleases to complement your research. More product information can be obtained for the products listed and others at sigma.com.

Antibodies to Calcium Channel Proteins

Product Name Host Clone No. Form Gene Symbol Species Reactivity Application Prestige Antibody Cat. No.

Anti-CACNA1C goat - affinity isolated antibody

CACNA1C, human human ELISA (i)WB

- SAB2500182-100UG

Anti-CACNA1C rabbit - affinity isolated antibody

CACNA1C, human human IHC (p)PA

✔ HPA039796-100UL

Monoclonal Anti-CACNA1C, (C-terminal)

mouse 4D10 purified immunoglobulin

CACNA1C, human human ELISA (c)ELISA (i)WB

- SAB1402709-100UG

Anti-Calcium Channel (α1 Subunit), Pan

rabbit - affinity isolated antibody

Cacna1c, ratCacna1c, mouse

mouserat

IHCWB

- C1103-.05MLC1103-.2ML

Anti-Calcium Channel (Cardiac α1C Subunit) (L-type of Voltage-gated Ca2+ Channel)

rabbit - affinity isolated antibody

Cacna1c, rat rabbitrat

IPWB CL

- C4980-.05MLC4980-.2ML

Anti-Calcium Channel (α1C Subunit) (L-type of Voltage-gated Ca2+ Channel)

rabbit - affinity isolated antibody

Cacna1c, mouse humanmouserabbitrat

IHCWB

- C1603-.2ML

Anti-Calcium Channel CaV1.2 (human)

rabbit - affinity isolated antibody

CACNA1C, humanCacna1c, ratCacna1c, mouse

mouserat

WB - C1241-200UL

CCBs – Approved Therapeutics (continued)

Order sigma.com/order Technical service sigma.com/techinfo sigma.com/lifescience 19

Biochemicals for Calcium Channel Research

Name Structure CAS No. Cat. No.

S-Petasin

CH3CH3

O

CH3

CH2O

O

SCH3

70238-51-6 P4243-1MGP4243-5MG

Phloretin O

HO

OH

OHHO

60-82-2 P7912-25MGP7912-100MGP7912-250MG

Protopine hydrochloride

NCH3

O

O

O

OO

• HCl

6164-47-2 P8489-5MG

Zinc Finger Nucleases for Calcium Channel Research

Name Gene Symbol Cat. No.

CompoZr® Knockout ZFN Kit CACNA1C CKOZFN2581-1KT

CompoZr® Knockout ZFN Kit, ZFN plasmid only Cacna1c CKOZFND27870-1KT

CompoZr® Knockout ZFN Kit, ZFN plasmid only CACNA1C CKOZFND2581-1KT

DiureticsFirst-line agents in the treatment of hypertension are the thiazide-type diuretics. These therapeutics are proven to reduce cardiovascular mortality and morbidity. This reduction occurs in both systolic and diastolic forms of hypertension.1

Hydrochlorothiazide (HCTZ) is the thiazide-type diuretic used most often. Another proven thiazide-type therapeutic is chlorthalidone, which resembles HCTZ structurally but differs in its pharmacology.2 These compounds are well tolerated antihypertensive agents with respect to symptomatic and adverse side effects.3

Loop diurectics such as fuorsemide, bumetanide, and torsemide are less effective than the thiazide-type drugs in reducing blood pressure. However, loop diuretics are important in hypertensive patients with significant fluid overload or advanced renal failure.4

Diuretics can be successfully combined with β-blockers, ACE inhibitors, ARBs, and CCBs. The combination of a diuretic with any one of these antihypertensive agents provides the best effect in lowering blood pressure when compared to combinations without a diuretic.5

You can obtain HCTZ and many of the loop diurectics from Sigma® Life Science at competitive prices. There are biomolecules and peptides also available at Sigma. We strive to provide you with the largest selection of products so you can focus more on your research.

You’re more likely to find the agents for your research needs at Sigma Life Scienve than anywhere else.

References1. Ernst et al. 2010. Meta-analysis of dose-response

characteristics of hydrochlorothiazide and chlorthalidone: effects on systolic blood pressure and potassium. Am J Hypertens 23:440-6.

2. Carter et al. 2004. Hydrochlorothiazide versus chlorthalidone: evidence supporting their interchangeability. Hypertension 43:4-9.

3. Psaty et al. 1997. Health outcomes associated with antihypertensive therapies used as first-line agents. A systematic review and meta-analysis. JAMA 277:739-45.

4. Vargo et al. 1995. Bioavailability, pharmacokinetics, and pharmacodynamics of torsemide and furosemide in patients with congestive heart failure. Clin Pharmacol Ther 57:601-9.

5. Materson et al. 1993. Single-drug therapy for hypertension in men: A comparison of six antihyper-tensive agents with placebo. N Engl J Med 328:914-21.

20

Diuretics – Approved Therapeutics and Biochemicals

Name Structure CAS No. Cat. No.

Hydrochlorothiazide

SNH

HN

O OS

Cl

H2NO

O

58-93-5 H4759-5GH4759-25GH4759-100G

Bumetanide NHCH2CH2CH2CH3

OC

O

HO

S OO

NH2

28395-03-1 B3023-250MGB3023-1G

Eplerenone

O

H3C

H3C

O

O

O

O

OCH3H H

107724-20-9 E6657-10MGE6657-50MG

Furosemide

O

HN

O OH

ClSH2NO

O

54-31-9 F4381-1GF4381-5GF4381-10GF4381-25G

SpironolactoneH3C

OHH3C

O SHH

O

CH3

O

52-01-7 S3378-1GS3378-5G

Triamterene

N

N

N

N

NH2

NH2H2N

396-01-0 T4143-10GT4143-25G

Metolazone

N

HN CH3

O

Cl

SH2N

OO

CH3

17560-51-9 M1195-5MGM1195-25MG

Pinoresinol

O

O H

H

OCH3

OH

OCH3

HO

487-36-5 SML0073-1MGSML0073-5MG

Atrial Natriuretic Peptides

Product Name Gene Symbol Purity CAS No. Cat. No.

Atrial Natriuretic Peptide fragment 4-24 frog anf-A ≥97%, HPLC 118691-44-4 A0804-.1MGA0804-.5MG

Atrial Natriuretic Peptide human NPPA ≥97%, HPLC 91917-63-4 A1663-.1MGA1663-.5MGA1663-1MG

Order sigma.com/order Technical service sigma.com/techinfo sigma.com/lifescience 21

Antilipemic AgentsHMG-CoA InhibitorsRandomized controlled clinical studies have suggested 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are effective in both primary and secondary prevention of cardiovascular disease (CVD) events.1 Primary prevention refers to interventions that obviate the first occurrence of a disease or condition, secondary interventions deter reoccurrence.

The use of statins for primary intervention is extensive for individuals with no previous CVD but who have both elevated cholesterol levels and high blood pressure, or individuals who have coronary heart disease plus multiple risk factors such as diabetes and high blood pressure.2

While cholesterol has been singled out as the primary factor in the development of atherosclerosis, some research studies

suggest that C-reactive protein (CRP) may also be a marker for the development and progression of atherosclerosis.3-5 Elevated basal levels of CRP can lead to inflammation of arterial vessels, increasing the risk of hypertension and cardiovascular disease.4

In 2010, rosuvastatin was approved in the U.S. to prevent CVD in individuals over 50 with normal low density lipid (LDL)-cholesterol levels and no history of heart disease, but elevated CRP levels coupled with one other risk factor such as high blood pressure.6

You can obtain seven statins from Sigma® Life Science, including the two drug candidates, mevastatin (Cat. No. M2537) and SR 12813 (Cat. No. S4194). We also offer complementary products such as antibodies, biomolecules, and zinc finger nucleases. Visit sigma.com to discover all the products relevant to your research.

References1. Pichandi et al. 2011. The role of statin drugs in combat-

ing cardiovascular diseases. Int J Cur Sci Res 1:47-56.2. Goldenberg, N. and Glueck, C. 2009. Efficacy, effective-

ness and real life goal attainment of statins in manag-ing cardiovascular risk. Vasc Hlth & Risk Mgmt 5:369-76.

3. Kleemann, R. and Kooistra, T. 2005. HMG-CoA reductase inhibitors: Effects on chronic subacute inflammation and onset of atherosclerosis induced by dietary choles-terol. Cardiovasc & Haem Disorders 5:441-53.

4. Danesh et al. 2004. C-reactive P-protein and other circulating markers of inflammation in the prediction of coronary heart disease. N Engl J Med 350:1387-97.

5. Levinson, S. 2006. Inflammatory and long-term risk markers. Clin Lab Med 26:553-70.

6. MacDonald, GP. 2010. Cost-effectiveness of rosuvastatin for primary prevention of cardiovascular events accord-ing to Framingham risk score in patients with elevated C-reactive protein. J Am Osteopath Assoc 110:427-36.

HMG-CoA Inhibitors – Approved Therapeutics

Name Structure CAS No. Cat. No.

Atorvastatin calcium salt trihydrate

N i-PrF

NH

O

HO

OH

O

O

2

• 3H2O

Ca2+

134523-03-8 (anhydrous)

PZ0001-5MGPZ0001-25MG

Cerivastatin sodium salt hydrate

NH3C

CH3

H3CO

F

CH3

CH3

ONa

OOHOH

• xH2O

143201-11-0 (anhydrous)

SML0005-5MGSML0005-25MG

Fluvastatin sodium hydrate

NONa

OOHOH

H3C CH3

• xH2O

F - SML0038-10MGSML0038-50MG

Antilipemic Agents

22

Name Structure CAS No. Cat. No.

Mevinolin from Aspergillus sp.

CH3CH2 CH CO

O

CH3H

CH2H

CH3

CH2

O

OHO

CH3

H

75330-75-5 M2147-25MG

Pravastatin sodium salt hydrate

CH3

HO

O

O

H3CH3C

HO

OH

H

H

O

NaO - P4498-25MG

Simvastatin

H3C

OCH3

H

OH3C

H3CH3C

O O

OH 79902-63-9 S6196-5MGS6196-25MG

HMG-CoA Inhibitor Drug Candidates

Name Structure CAS No. Cat. No.

Mevastatin

CH3CH2 CH CO

O

CH3

HCH2

HCH3

CH2

O

OHO

H

73573-88-3 M2537-5MG

SR 12813HO

P(O)(OC2H5)2

P(O)(OC2H5)2H3C

H3CH3C

CH3

H3C CH3 126411-39-0 S4194-1MGS4194-5MG

Antibodies To HMG-CoA Enzymes

Product Name Host Form Gene Symbol Species Reactivity Application Prestige Antibody Cat. No.

Anti-HMGCL rabbit affinity isolated antibody HMGCL, human human IHC (p)PAWB

✔ HPA004727-100UL

Anti-HMGCR rabbit affinity isolated antibody HMGCR, human human IHC (p)PA

✔ HPA008338-100UL

HMG-CoA Inhibitors – Approved Therapeutics (continued)

Order sigma.com/order Technical service sigma.com/techinfo sigma.com/lifescience 23

Biochemicals for HMG-CoA Research

Name Structure CAS No. Cat. No.

3-Hydroxy-3-methylglutaryl-CoA reductase human

- - H7039-250UG

DL-3-Hydroxy-3-methylglutaryl coenzyme A sodium salt hydrate N

N N

N

NH2

O

O

OPOOH

O

OH

P

O

OHO

H3C CH3O

HN

NH

OH

O

S

O

OH

OHO CH3

PNaOO

ONa

• xH2O

- H6132-5MGH6132-10MGH6132-25MG

Matairesinol

O O

H3CO

OCH3

OHHO

580-72-3 40043-5MG-F

(±)-Naringenin

O

OH

HO

OH O 67604-48-2 N5893-1GN5893-5GN5893-25G

Sesamin

O

OH

H

O

O

O

O

607-80-7 S9314-5MG

Zinc Finger Nucleases for HMG-CoA Research

Name Gene Symbol Cat. No.

CompoZr® Knockout ZFN Kit HMGCR CKOZFN10166-1KT

CompoZr® Knockout ZFN Kit, ZFN plasmid only Hmgcr CKOZFND33342-1KT

CompoZr® Knockout ZFN Kit, ZFN plasmid only Hmgcr CKOZFND55090-1KT

CompoZr® Knockout ZFN Kit, ZFN plasmid only HMGCR CKOZFND10166-1KT

PPAR ActivatorsPeroxisome proliferator-activated receptors (PPAR) are nuclear receptors that function as transcription factors on targeted genes when heterodimerized with the retinoid X receptor.1

PPAR-α is mainly involved in fatty acid oxidation and is expressed in the liver, kidney, and skeletal muscle, while PPAR-γ is primarily involved in fat cell differentiation and insulin sensitivity.2 Both are expressed in smooth muscle cells and myocardium.

PPAR agonists have been shown to reduce blood pressure in several models of hypertension, correct endothelial dysfunction, and exert anti-inflammatory actions.3-5 Therefore, these therapeutic agents are used to prevent vascular and cardiac complications associated with hypertension.

References1. Francis et al. 2003. PPAR agonists in the treatment of

atherosclerosis. Curr Opin Pharmacol 3:186-91.2. Calkin, AC and Thomas, MC. 2007. PPAR agonists and

cardiovasuclar disease in diabetes. PPAR Research 2008:1-12.

3. Buchan, KW and Hassall, DG. 2000. PPAR agonists as direct modulators of the vessel wall in cardiovascular disease. Med Res Rev 20:350-66.

4. Inoue et al. 1998. Expression of peroxisome proliferator-activated receptor α in primary cultures of human vascular endothelial cells. Biochem Biophys Res Commun 246: 370-4.

5. Vu-Dac et al. 1998. The nuclear receptors peroxisome proliferator-activated receptor α and Rev-erbα mediate the species-specific regulation of apolipoprotein A-I expression by fibrates. J Biol Chem 273:25713-20.

24

PPAR Activators – Approved Therapeutics

Name Structure CAS No. Cat. No.

Clofibrate

Cl

OO CH3

H3C CH3

O 637-07-0 C6643-250MGC6643-1GC6643-5GC6643-10G

Fenofibrate

Cl

O

O

O O

CH3

CH3

CH3

CH3

49562-28-9 F6020-5GF6020-25GF6020-100G

Gemfibrozil

O

CH3

H3C OHCH3H3C

O25812-30-0 G9518-5G

G9518-25G

ACAT InhibitorsThe enzyme acyl-coenzyme A:cholesterol acyltransferase (ACAT) esterifies cholesterol in a variety of tissues. In some animal models, ACAT inhibitors act alone or in combination with HMG-CoA inhibitors to exert their antiatherosclerotic effects.1 This effect is

presumed to occur through the regulation of cholesterol trafficking pathways in the liver and vascular cells.2

Visit sigma.com/therapeutics for a listing of the many approved therapeutics and drug candidates available for your cardiovascular research.

References1. Nissen et al. 2006. Effect of ACAT inhibition on the

progression of coronary atherosclerosis. N Engl J Med 354:1253-63.

2. Bocan et al. 1998. HMG-CoA reductase and ACAT inhibitors act synergistically to lower plasma choles-terol and limit atherosclerotic lesion development in the cholesterol-fed rabbit. Atherosclerosis 139:21-30.

ACAT Inhibitor Drug Candidates

Name Structure CAS No. Cat. No.

Avasimibe

SO

OON

Hi-Pr

i-PrO

i-Pr

i-Pr i-Pr 166518-60-1 PZ0190-5MGPZ0190-25MG

Sandoz 58-035 HN

H3CO

Si CH2(CH2)8CH3

CH3

CH3

78934-83-5 S9318-5MGS9318-25MG

Order sigma.com/order Technical service sigma.com/techinfo sigma.com/lifescience 25

Anticoagulants – Approved Therapeutics and Drug Candidates

Name Structure CAS No. Cat. No.

Acenocoumarol

O O

OH

NO2

O

CH3

152-72-7 SML0074-10MGSML0074-50MG

Argatroban monohydrate - 141396-28-3 A0487-5MGA0487-25MG

(S)-(+)-Clopidogrel hydrogensulfate

N

S

O OCH3Cl

• H2SO2

120202-66-6 SML0004-10MGSML0004-50MG

GSK-429286 - 864082-47-3 SML0231-5MGSML0231-25MG

Prostaglandin I2 sodium saltO O-

O

OH

Na+

OH

(CH2)4CH3

HH

61849-14-7 P6188-1MGP6188-5MGP6188-10MG

Triflusal - 322-79-2 T6580-5MGT6580-25MG

AnticoagulantsPulmonary arterial hypertension (PAH) is characterized as a progressive, incurable disease and its treatment remains elusive.1 The mean survival rate is often less than 4 years and the median survival period is 2.8 years.2

In the 1980s, one treatment of PAH focused on anticoagulant therapy. Fuster et al. reported a statistically significant improvement in the survival of patients who had been treated with warfarin compared to patients who had received no anticoagulants.3 Rich et al. found the use of anticoagulants may benefit patients with PAH who do not respond to therapy with calcium-channel blockers.4

Novel approaches to treat PAH include Rho-kinase inhibitors and soluble guanylate cyclase stimulators.5 Animal models have

shown these new classes of agents mitigate the abnormal pulmonary vasoconstriction associated with the disease.

Sigma® Life Science is the source for all five approved anticoagulants listed below. Sigma Life Science also offers the drug candidate GSK-429286 (Cat. No. SML0231), a ROCK1 inhibitor from GSK, the approved drug Sildenafil (Cat. No. PZ0003), a guanylate cyclase activator from Pfizer, and the powerful anticoagulant heparin (Cat. No. H3393).

Basic scientific research plays an important role in finding new discoveries to improve the quality of life for individuals affected with this disease. We are working diligently to provide you with the needed tools for your research endeavors.

Visit sigma.com/therapeutics for a listing of approved compounds and drug candidates available for your cardiovascular research.

References1. Johnson et al. 2006. Thrombotic arteriopathy and

anticoagulation in pulmonary hypertension. Chest 130:545-52.

2. Roger et al. 2011. Heart disease and stroke statis-tics–2011 update : A report from the American Heart Association. Circulation 123:e18-e209.

3. Fuster et al. 1984. Primary pulmonary hypertension: Natural history and the importance of thrombosis. Circulation 70:580-7.

4. Rich et al. 1992. The effect of high doses of calcium-channel blockers on survival in primary pulmonary hypertension. N Engl J Med 327:76- 81.

5. Murthy et al. 2010. New approaches to the treatment of pulmonary hypertension: from bench to bedside. Cardiol Rev. 8: 76-84.

Anticoagulants

26

Other products that complement our approved anticoagulants include antibodies, biomolecules, and peptides. Visit sigma.com to search our entire catalog and obtain more information for any of our products.

Antibody to Prothrombin IIA

Product Name Host Form Gene Symbol Species Reactivity Application Prestige Antibody Cat. No.

Monoclonal Anti-PROC mouse purified immunoglobulin PROC, human human ELISA (i)WB

- WH0005624M1-50UG

Anti-PROC rabbit IgG fraction of antiserum PROC, human bovinehuman

WB - AV41701-100UG

Anti-PROC rabbit affinity isolated antibody PROC, human human IHC (p)PA

✔ HPA005550-100UL

Biochemicals for Coagulation Research

Name Structure CAS No. Cat. No.

Heparin sodium salt from porcine intestinal mucosa

- 9041-08-1 H3393-10KUH3393-25KUH3393-50KUH3393-100KUH3393-250KUH3393-500KUH3393-1MU

Oxolamine citrate salt

NN

ONHO OH

O OOH

O OH

1949-20-8 O2256-25G

Paeoniflorin

O OHO

CH3

O

O

H

HO O

HO OHOH

OH

23180-57-6 P0038-25MG

Sildenafil citrate salt

HN

N

O

NNCH3

CH3

O CH3

SO

NO

NH3C OH

O

OHHO

OOHO

•

171599-83-0 PZ0003-5MGPZ0003-25MG

Proteins and Peptides for Coagulation Research

Product Name Gene Symbol Purity CAS No. Cat. No.

[Tyr(SO3H)63]-Hirudin Fragment 54-65 - ≥95%, HPLC 109528-49-6 H6894-.1MGH6894-1MG

Protein C, Activated, Fragment 390-404 human PROC ~90%, HPLC - P5818-.5MG

Protein C from human plasma PROC ≥90%, SDS-PAGE 42617-41-4 P2200-.1MG

Application Abbreviation Table

Application AbbreviationAgglutination assay Agglut.ANA-indirect immunofluorescence IF (ANA)Array (antibody microarray) ARRCapture ELISA ELISA (c)Direct ELISA ELISA (d)Direct immunofluorescence IF (d)Dot blot DBDot immunobinding DIBAElectron microscopy EMEnzyme immunoassay EIAFlow cytometry FACSImmunoblotting WBImmunoblotting (chemiluminescent) WB CLImmunocytochemistry ICC

Application AbbreviationImmunoelectrophoresis IEPImmunohistochemistry IHCImmunohistochemistry (formalin-fixed, paraffinembedded sections) IHC (p)Immunohistochemistry (frozen sections) IHC (f )Immunoprecipitation IPIndirect ELISA ELISA (i)Indirect immunofluorescence IF (i)Neutralization NeutralOuchterlony double diffusion ODDParticle immunofluorescence PIFAProtein Array PAQuantitative precipitin assay QPARadioimmunoassay RIA

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