title: Lead optimization attrition analysis (LOAA): a novel and general methodology for medicinal chemistry.
abstract: Herein, we report a novel and general method, lead optimization attrition analysis (LOAA), to benchmark two distinct small-molecule lead series using a relatively unbiased, simple technique and commercially available software. We illustrate this approach with data collected during lead optimization of two independent oncology programs as a case study. Easily generated graphics and attrition curves enabled us to calibrate progress and support go/no go decisions on each program. We believe that this data-driven technique could be used broadly by medicinal chemists and management to guide strategic decisions during drug discovery.
authors: Lead Generation Candidate Realization, Sanofi, 153 Second Avenue, Waltham, MA 02451, USA. Electronic address: mark.munson@sanofi.com.
authors: Mark
authors: M
authors: Munson
authors: Lead Generation Candidate Realization, Sanofi, 153 Second Avenue, Waltham, MA 02451, USA.
authors: Harvey
authors: H
authors: Lieberman
authors: Information Solutions, Sanofi, 640 Memorial Drive, Cambridge, MA 02139, USA.
authors: Elina
authors: E
authors: Tserlin
authors: Oncology, Sanofi, 640 Memorial Drive, Cambridge, MA 02139, USA.
authors: Jennifer
authors: J
authors: Rocnik
authors: Oncology, Sanofi, 640 Memorial Drive, Cambridge, MA 02139, USA.
authors: Jie
authors: J
authors: Ge
authors: DMPK, Sanofi, 153 Second Avenue, Waltham, MA 02451, USA.
authors: Maria
authors: M
authors: Fitzgerald
authors: Lead Generation Candidate Realization, Sanofi, 153 Second Avenue, Waltham, MA 02451, USA.
authors: Vinod
authors: V
authors: Patel
authors: Lead Generation Candidate Realization, Sanofi, 94400 Vitry sur Seine, France.
authors: Carlos
authors: C
authors: Garcia-Echeverria
mesh_terms: D000465:Algorithms; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D001681:Biological Assay; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003661:Decision Support Techniques; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D008954:Models, Biological; D015233:Models, Statistical; D012984:Software
chemical_list: D000970:Antineoplastic Agents