SAR125844

• CAT Number: I009283
• CAS Number: 1116743-46-4
• Molecular Formula: C25H23FN8O2S2
• Molecular Weight: 550.631
• Purity: ≥95%
• Target: c-MET inhibitor
• Solubility: Soluble in DMSO, not in water
• Storage: 0 - 4 °C for short term, or -20 °C for long term
• IUPAC Name: 1-[6-[[6-(4-fluorophenyl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl]sulfanyl]-1,3-benzothiazol-2-yl]-3-(2-morpholin-4-ylethyl)urea
• InChI: InChI=1S/C25H23FN8O2S2/c26-17-3-1-16(2-4-17)19-7-8-22-30-31-25(34(22)32-19)37-18-5-6-20-21(15-18)38-24(28-20)29-23(35)27-9-10-33-11-13-36-14-12-33/h1-8,15H,9-14H2,(H2,27,28,29,35)
• InChIKey: ODIUNTQOXRXOIV-UHFFFAOYSA-N
• SMILES: C1COCCN1CCNC(=O)NC2=NC3=C(S2)C=C(C=C3)SC4=NN=C5N4N=C(C=C5)C6=CC=C(C=C6)F

SAR125844 is a potent and highly selective c-Met inhibitor with potential antineoplastic activity. Upon intravenous administration, SAR125844 binds to c-Met, thereby disrupting c-Met-mediated signal transduction pathways. SAR125844 displayed nanomolar activity against the wild-type kinase (IC50 value of 4.2 nmol/L) and the M1250T and Y1235D mutants. Broad biochemical profiling revealed that SAR125844 was highly selective for MET kinase. SAR125844 inhibits MET autophosphorylation in cell-based assays in the nanomolar range, and promotes low nanomolar proapoptotic and antiproliferative activities selectively in cell lines with MET gene amplification or pathway addiction.

Overview of Clinical Research

Originator: Sanofi
Class: Antineoplastics
Mechanism of Action: Proto oncogene protein c met inhibitors
Orphan Drug Status: No
New Molecular Entity: Yes

Reference

1:Discovery and Pharmacokinetic and Pharmacological Properties of the Potent and Selective MET Kinase Inhibitor 1-{6-[6-(4-Fluorophenyl)-[1,2,4]triazolo[4,3-b]pyridazin-3-ylsulfanyl]benzothiazol-2-yl}-3-(2-morpholin-4-ylethyl)urea (SAR125844). Ugolini A, Kenigsberg M, Rak A, Vallée F, Houtmann J, Lowinski M, Capdevila C, Khider J, Albert E, Martinet N, Nemecek C, Grapinet S, Bacqué E, Roesner M, Delaisi C, Calvet L, Bonche F, Semiond D, Egile C, Goulaouic H, Schio L.J Med Chem. 2016 Aug 11;59(15):7066-74. doi: 10.1021/acs.jmedchem.6b00280. Epub 2016 Jul 13. PMID: 27355974
2:The selective intravenous inhibitor of the MET tyrosine kinase SAR125844 inhibits tumor growth in MET-amplified cancer. Egile C, Kenigsberg M, Delaisi C, Bégassat F, Do-Vale V, Mestadier J, Bonche F, Bénard T, Nicolas JP, Valence S, Lefranc C, Francesconi E, Castell C, Lefebvre AM, Nemecek C, Calvet L, Goulaouic H.Mol Cancer Ther. 2015 Feb;14(2):384-94. doi: 10.1158/1535-7163.MCT-14-0428. Epub 2014 Dec 10. PMID: 25504634 Free Article