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(A) GPCR-targeting drugs in top 20 (B) First-in-class drugs (after 2010)
Rank Name Disease Targets 2 Clopidogrel Thrombosis P2Y12
7 Salmeterol Asthma β2
9 Valsartan Hypertension AT1
10 Quetiapine chizophrenia D2, 5-HT2
11 Montelukast Asthma CysLT1
12 Aripiprazole chizophrenia D2, 5-HTR
18 Olanzapine chizophrenia D2, 5-HTR
20 Candesartan Hypertension AT1
World sales in 2011 (more than $4 billion) From Cegedim Strategic Data
Name Disease Targets
Fingolimod Multiple sclerosis S1P1
Mogamulizu-mab
T cell lymphoma CCR4
Lorcaserin Obesity 5-HT2C
Mirabegron Incontinence β3
Icatibant Angioedema B2
Vismodegib Cancer SMO
Ramelteon Insomnia MT1, 2
From Nat. Rev. Drug Discov. and ChEMBL databases
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Figure 19-26 Essential Cell Biology (© Garland Science 2010)
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674 PANEL 19–1 Some essentials of classical genetics
TWO GENES OR ONE?Given two mutations that produce the same phenotype, how can we tell whether they are mutations in the same gene? If the mutations are recessive (as they most often are), the answer can be found by a complementation test.
In the simplest type of complementation test, an individual who is homozygous for one mutation is mated with an individual who is homozygous for the other. The phenotype of the offspring gives the answer to the question.
COMPLEMENTATION:MUTATIONS IN TWO DIFFERENT GENES
homozygous mutant mother homozygous mutant father
hybrid offspring shows normal phenotype:one normal copy of each gene is present
NONCOMPLEMENTATION:TWO INDEPENDENT MUTATIONS IN THE SAME GENE
homozygous mutant mother homozygous mutant father
hybrid offspring shows mutant phenotype:no normal copies of the mutated gene are present
GENES AND PHENOTYPES Gene: a functional unit of inheritance, usually corresponding to the segment of DNA coding for a single protein. Genome: all of an organism’s DNA sequences.
locus: the site of the gene in the genome
alleles: alternative forms of a gene Wild type: the normal,naturally occurring type
Mutant: differing from thewild type because of a geneticchange (a mutation)
GENOTYPE: the specific set of alleles forming the genome of an individual
PHENOTYPE: the visible character of the individual
allele A is dominant (relative to a); allele a is recessive (relative to A)
homozygous A/A heterozygous a/A homozygous a/a
In the example above, the phenotype of the heterozygote is the same as that of one of thehomozygotes; in cases where it is different from both, the two alleles are said to be co-dominant.
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MEIOSIS ANDRECOMBINATION
The greater the distance between two loci on a single chromosome, the greater is the chance that they will be separated by crossing-over occurring at a site between them. If two genes are thus reassorted in x% of gametes, they are said to be separated on a chromosome by a genetic map distance of x map units (or x centimorgans).
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Figure 10-36 (part 2 of 2) Essential Cell Biology (© Garland Science 2010)
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