BMS-536924

• CAT Number: I003623
• CAS Number: 468740-43-4
• Molecular Formula: C₂₅H₂₆ClN₅O₃
• Molecular Weight: 479.96
• Purity: ≥95%
• Target: IGF1R
• Solubility: DMSO 96 mg/ml; Water < 1 mg/ml
• Storage: 3 years -20℃ powder
• IC50: 100 nM (IGF-1R); 73 nM (IR) [1]
• IUPAC Name: 4-[[(2S)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-(4-methyl-6-morpholin-4-yl-1H-benzimidazol-2-yl)-1H-pyridin-2-one
• InChI: InChI=1S/C25H26ClN5O3/c1-15-11-18(31-7-9-34-10-8-31)13-20-23(15)30-24(29-20)22-19(5-6-27-25(22)33)28-14-21(32)16-3-2-4-17(26)12-16/h2-6,11-13,21,28-30,32H,7-10,14H2,1H3/b24-22-/t21-/m1/s1
• InChIKey: UGQMURPIMYALPH-KKPVDXMRSA-N
• SMILES: CC1=CC(=CC2=C1NC(=C3C(=CC=NC3=O)NCC(C4=CC(=CC=C4)Cl)O)N2)N5CCOCC5

BMS-536924 (Cat.No:I003623) is an ATP-competitive inhibitor of insulin-like growth factor-1 receptor (IGF-1R) with an IC50 of 100nM. It exhibits moderate inhibitory activity against Mek, Fak, and Lck, but almost no inhibitory activity against Akt1 and MAPK1/2. IGF-1R plays an important role in regulating reproductive neuroendocrine function in the brain, and is located in various tissues such as the ovaries and brain.

Reference

1:BMS-536924, an ATP-competitive IGF-1R/IR inhibitor, decreases viability and migration of temozolomide-resistant glioma cells in vitro and suppresses tumor growth in vivo. Zhou Q.Onco Targets Ther. 2015 Apr 2;8:689-97. doi: 10.2147/OTT.S80047. eCollection 2015. PMID: 25897243 Free PMC Article2:IGF1/insulin receptor kinase inhibition by BMS-536924 is better tolerated than alloxan-induced hypoinsulinemia and more effective than metformin in the treatment of experimental insulin-responsive breast cancer. Dool CJ, Mashhedi H, Zakikhani M, David S, Zhao Y, Birman E, Carboni JM, Gottardis M, Blouin MJ, Pollak M.Endocr Relat Cancer. 2011 Nov 14;18(6):699-709. doi: 10.1530/ERC-11-0136. Print 2011 Dec. PMID: 21946410 Free Article3:Drug efflux by breast cancer resistance protein is a mechanism of resistance to the benzimidazole insulin-like growth factor receptor/insulin receptor inhibitor, BMS-536924. Hou X, Huang F, Carboni JM, Flatten K, Asmann YW, Ten Eyck C, Nakanishi T, Tibodeau JD, Ross DD, Gottardis MM, Erlichman C, Kaufmann SH, Haluska P.Mol Cancer Ther. 2011 Jan;10(1):117-25. doi: 10.1158/1535-7163.MCT-10-0438. PMID: 21220496 Free PMC Article4:Expression of insulin receptor isoform A and insulin-like growth factor-1 receptor in human acute myelogenous leukemia: effect of the dual-receptor inhibitor BMS-536924 in vitro. Wahner Hendrickson AE, Haluska P, Schneider PA, Loegering DA, Peterson KL, Attar R, Smith BD, Erlichman C, Gottardis M, Karp JE, Carboni JM, Kaufmann SH.Cancer Res. 2009 Oct 1;69(19):7635-43. doi: 10.1158/0008-5472.CAN-09-0511. Epub 2009 Sep 29. PMID: 19789352 Free PMC Article5:BMS-536924 sensitizes human epithelial ovarian cancer cells to the PARP inhibitor, 3-aminobenzamide. Beauchamp MC, Knafo A, Yasmeen A, Carboni JM, Gottardis MM, Pollak MN, Gotlieb WH.Gynecol Oncol. 2009 Nov;115(2):193-8. doi: 10.1016/j.ygyno.2009.07.009. Epub 2009 Aug 21. PMID: 19699512 6:BMS-536924 reverses IGF-IR-induced transformation of mammary epithelial cells and causes growth inhibition and polarization of MCF7 cells. Litzenburger BC, Kim HJ, Kuiatse I, Carboni JM, Attar RM, Gottardis MM, Fairchild CR, Lee AV.Clin Cancer Res. 2009 Jan 1;15(1):226-37. doi: 10.1158/1078-0432.CCR-08-0801. PMID: 19118050 Free PMC Article7:The mechanisms of differential sensitivity to an insulin-like growth factor-1 receptor inhibitor (BMS-536924) and rationale for combining with EGFR/HER2 inhibitors. Huang F, Greer A, Hurlburt W, Han X, Hafezi R, Wittenberg GM, Reeves K, Chen J, Robinson D, Li A, Lee FY, Gottardis MM, Clark E, Helman L, Attar RM, Dongre A, Carboni JM.Cancer Res. 2009 Jan 1;69(1):161-70. doi: 10.1158/0008-5472.CAN-08-0835. PMID: 19117999 Free Article8:HER receptor signaling confers resistance to the insulin-like growth factor-I receptor inhibitor, BMS-536924. Haluska P, Carboni JM, TenEyck C, Attar RM, Hou X, Yu C, Sagar M, Wong TW, Gottardis MM, Erlichman C.Mol Cancer Ther. 2008 Sep;7(9):2589-98. doi: 10.1158/1535-7163.MCT-08-0493. Epub 2008 Sep 2. PMID: 18765823 Free PMC Article9:2-(1H-Imidazol-4-yl)ethanamine and 2-(1H-pyrazol-1-yl)ethanamine side chain variants of the IGF-1R inhibitor BMS-536924. Saulnier MG, Frennesson DB, Wittman MD, Zimmermann K, Velaparthi U, Langley DR, Struzynski C, Sang X, Carboni J, Li A, Greer A, Yang Z, Balimane P, Gottardis M, Attar R, Vyas D.Bioorg Med Chem Lett. 2008 Mar 1;18(5):1702-7. doi: 10.1016/j.bmcl.2008.01.049. Epub 2008 Jan 18. PMID: 18258427 10:Discovery of a (1H-benzoimidazol-2-yl)-1H-pyridin-2-one (BMS-536924) inhibitor of insulin-like growth factor I receptor kinase with in vivo antitumor activity. Wittman M, Carboni J, Attar R, Balasubramanian B, Balimane P, Brassil P, Beaulieu F, Chang C, Clarke W, Dell J, Eummer J, Frennesson D, Gottardis M, Greer A, Hansel S, Hurlburt W, Jacobson B, Krishnananthan S, Lee FY, Li A, Lin TA, Liu P, Ouellet C, Sang X, Saulnier MG, Stoffan K, Sun Y, Velaparthi U, Wong H, Yang Z, Zimmermann K, Zoeckler M, Vyas D.J Med Chem. 2005 Sep 8;48(18):5639-43. PMID: 16134929