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: /nrd2199

Druggable Proteome Door: Protein Lock: Drug Binding Site Key: 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: /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):  Hopkins AL and Groom CR (2002) The druggable genome, Nat Rev Drug Discov 1: