We previously published on the design and synthesis of novel, potent and selective PPARα antagonists suitable for either i.p. or oral in vivo administration for the potential treatment of cancer. Described herein is SAR for a subsequent program, where we set out to identify selective and potent PPARα/δ dual antagonist molecules. Emerging literature indicates that both PPARα and PPARδ antagonism may be helpful in curbing the proliferation of certain types of cancer. This dual antagonism could also be used to study PPARs in other settings. After testing for selective and dual potency, off-target counter screening, metabolic stability, oral bioavailability and associated toxicity, compound 11, the first reported PPARα/δ dual antagonist was chosen for more advanced preclinical evaluation.
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Date of publication: 21 December 2018; Bioorganic & Medicinal Chemistry Letters
Author information: Jason D. Jacintho (1); Christopher S. Baccei (1); Yalda Bravo (1); Alex Broadhead (1); Austin Chen (1); Lucia Correa (1); Kim Fischer (1); Bryan Laffitte (1); Catherine Lee (1); Daniel S. Lorrain (1); Davorka Messmer (1); Peppi Prasit (1); Karin J. Stebbins (1); & Nicholas S. Stock (1)
(1) Inception Sciences, 5871 Oberlin Drive, Suite 100, San Diego, CA 92121, USA