LY-3200882

• CAT Number: I008779
• CAS Number: 1898283-02-7
• Molecular Formula: C24H29N5O3
• Molecular Weight: 435.528
• Purity: ≥95%
• Synonyms: LY-3200882; LY 3200882; LY3200882
• Target: TGF-β Receptor
• Storage: RT
• IUPAC Name: 2-[4-[[4-[1-cyclopropyl-3-(oxan-4-yl)pyrazol-4-yl]oxypyridin-2-yl]amino]pyridin-2-yl]propan-2-ol
• InChI: InChI=1S/C24H29N5O3/c1-24(2,30)21-13-17(5-9-25-21)27-22-14-19(6-10-26-22)32-20-15-29(18-3-4-18)28-23(20)16-7-11-31-12-8-16/h5-6,9-10,13-16,18,30H,3-4,7-8,11-12H2,1-2H3,(H,25,26,27)
• InChIKey: PNPFMWIDAKQFPY-UHFFFAOYSA-N
• SMILES: CC(O)(C)C1=NC=CC(NC2=NC=CC(OC3=CN(C4CC4)N=C3C5CCOCC5)=C2)=C1

LY-3200882 (CAT: I008779) is indeed an orally active TGF-beta inhibitor. It specifically targets and binds to TGF-beta, blocking its interaction with the TGF-beta receptor (TGF-betaR) and inhibiting downstream signaling. This interference with the TGF-beta signaling pathway can potentially disrupt various cellular processes involved in cancer progression, including cell proliferation, differentiation, apoptosis, migration, invasion, and angiogenesis. LY-3200882 shows promise as a therapeutic agent with potential antineoplastic activity by targeting the dysregulated TGF-beta pathway in cancer cells.

Overview of Clinical Research

LY-3200882 is a transforming growth factor beta type I receptor antagonist. Eli Lilly withdrew a phase I/II trial in Cancer (Combination therapy, Late-stage disease) in USA prior to enrolment, due to strategic realignment (PO) (NCT04158700) in 2020.

Reference

1. Preparation of aminopyridyloxypyrazole compounds as TGFβR1 inhibitors
By McMillen, William T.; Joseph, Sajan; Parthasarathy, Saravanan; Pei, Huaxing; Sawyer, Jason Scott; Beight, Douglas W.; Zhao, Gaiying; Coates, David A.; Wolfangel, Craig D. From U.S. Pat. Appl. Publ. (2016), US 20160096823 A1 20160407, Language: English, Database: CAPLUS
The title compds. I [R1 = H, iso-Pr, difluoromethyl, difluoroethyl, cyclopropyl; R2 = Et, tert-Bu, pyridin-2-yl, etc.; R3 = carbamoylphenyl, pyridine-2-yl, (1-hydroxy-1-methylethyl)pyridinyl, etc.] that inhibit the activity of transforming growth factor beta receptor 1 (TGFβR1), and therefore are can be used in treating cancer, preferably colon cancer, melanoma, hepatocellular carcinoma, renal cancer, glioblastoma, pancreatic cancer, myelodysplastic syndrome, lung cancer, and gastric cancer, and/or fibrosis, preferably liver fibrosis and chronic kidney disease, were prepd. E.g., a multi-step synthesis of II, starting from tetrahydropyran-4-carboxylic acid, was described. Exemplified compds. I were tested for their TGFβR1 activity, and demonstrated IC50 values less than 1 μM. Specifically, the IC50 for II is 0.0824 μM (±0.005, n=2). Pharmaceutical compn. comprising I is disclosed.