DRUGGABLE GENOME AND PROTEOME

Karen A. Méndez L

“the most fruitful basis for the discovery of a new drug is to start with an old drug” (James W Black,

Nobel de Medicina 1988)

Druggability

Thomas H Keller, et al. Current Opinion in Chemical Biology 2006, 10:357–361

Drug- like compounds

Thomas H Keller, et al. Current Opinion in Chemical Biology 2006, 10:357–361

Lipinski (2001) --˃ Rule of 5 (RO5)

Rule of 5

1. RO5 applies only to compounds that are delivered by the oral route.

2. RO5 applies only to compounds that are absorbed by passive mechanisms

3. There are important exceptions (MW and natural compounds).

4. RO5 compliant compounds are not automatically good drugs

Disease and Druggable Genome

Dixon SJ and Stockwell BR (2009)

Hopkins y Groom (2002)

Overington et al. Nature Reviews Drug Discovery 5, 993–996 (December 2006) | doi:10.1038/nrd2199

Druggable Proteome

Door: ProteinLock: Drug Binding SiteKey: Drug

Pharmaceutically Tractable Genome

Yıldırım et al, Drug–target network. NATURE BIOTECHNOLOGY VOLUME 25 NUMBER 10 OCTOBER 2007

Druggable Network

Yıldırım et al, Drug–target network. NATURE BIOTECHNOLOGY VOLUME 25 NUMBER 10 OCTOBER 2007

Distribution of Drugs and Drug Targets

Yıldırım et al, Drug–target network. NATURE BIOTECHNOLOGY VOLUME 25 NUMBER 10 OCTOBER 2007

Distribution of Drugs and Drug Targets

Yıldırım et al, Drug–target network. NATURE BIOTECHNOLOGY VOLUME 25 NUMBER 10 OCTOBER 2007

References

Dixon SJ and Stockwell BR (2009) Identifying druggable disease-modifying gene products, Curr Opin Chem Biol 13: 549–555

Yıldırım et al, Drug–target network. NATURE BIOTECHNOLOGY VOLUME 25 NUMBER 10 OCTOBER 2007

Overington et al. Nature Reviews Drug Discovery 5, 993–996 (December 2006) | doi:10.1038/nrd2199

Thomas H Keller, et al. Current Opinion in Chemical Biology 2006, 10:357–361

Zheng CJ et al. (2006) Therapeutic Targets: Progress of Their Exploration and Investigation of Their Characteristics,

Pharmacol Rev 58: 259–279 Russ AP and Lampel S (2005) The druggable genome:an

update, Drug Discov Today 10 (23/24): 1607-1610 Hopkins AL and Groom CR (2002) The druggable genome,

Nat Rev Drug Discov 1: 727-730