WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 406235
CAS#: 468741-42-6 (BMS-554417)
Description: BMS-554417 is a novel inhibitor of IGF-IR, which inhibits IGF-IR and insulin receptor kinase activity and proliferation in vitro, and reduces tumor xenograft size in vivo. In a series of carcinoma cell lines, the IC50 for proliferation ranged from 120 nmol/L (Colo205) to >8.5 micromol/L (OV202). BMS-554417 treatment inhibited IGF-IR and insulin receptor signaling through extracellular signal-related kinase as well as the phosphoinositide 3-kinase/Akt pathway, as evidenced by decreased Akt phosphorylation at Ser473. At doses that inhibited proliferation, the compound also caused a G0-G1 arrest and prevented nuclear accumulation of cyclin D1 in response to LR3 IGF-I. In Jurkat T-cell leukemia cells, this agent triggered apoptotic cell death via the mitochondrial pathway. BMS-554417 was orally bioavailable and significantly inhibited the growth of IGF1R-Sal tumor xenografts in vivo. BMS-554417 is a member of a novel class of IGF-IR/insulin receptor inhibitors that have potential clinical applications because of their antiproliferative and proapoptotic activity in vitro and in vivo.
MedKoo Cat#: 406235
CAS#: 468741-42-6 (BMS-554417)
Chemical Formula: C28H30ClN7O2
Exact Mass: 531.21495
Molecular Weight: 532.04
Elemental Analysis: C, 63.21; H, 5.68; Cl, 6.66; N, 18.43; O, 6.01
Synonym: BMS554417; BMS 554417; BMS-554417.
IUPAC/Chemical Name: (S)-3-(4-(2-(4-(2-(3-chlorophenyl)-2-hydroxyethylamino)-2-oxo-1,2-dihydropyridin-3-yl)-7-methyl-1H-benzo[d]imidazol-5-yl)piperazin-1-yl)propanenitrile
InChi Key: VVIPLSCLYCWUQT-XMMPIXPASA-N
InChi Code: InChI=1S/C28H30ClN7O2/c1-18-14-21(36-12-10-35(11-13-36)9-3-7-30)16-23-26(18)34-27(33-23)25-22(6-8-31-28(25)38)32-17-24(37)19-4-2-5-20(29)15-19/h2,4-6,8,14-16,24,37H,3,9-13,17H2,1H3,(H,33,34)(H2,31,32,38)/t24-/m1/s1
SMILES Code: N#CCCN1CCN(C2=CC(C)=C3NC(C4=C(NC[C@H](C5=CC=CC(Cl)=C5)O)C=CNC4=O)=NC3=C2)CC1
1: Ozkan EE. Plasma and tissue insulin-like growth factor-I receptor (IGF-IR) as a prognostic marker for prostate cancer and anti-IGF-IR agents as novel therapeutic strategy for refractory cases: a review. Mol Cell Endocrinol. 2011 Sep 15;344(1-2):1-24. doi: 10.1016/j.mce.2011.07.002. Epub 2011 Jul 18. Review. PubMed PMID: 21782884.
2: 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. 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. Mol Cancer Ther. 2011 Jan;10(1):117-25. doi: 10.1158/1535-7163.MCT-10-0438. PubMed PMID: 21220496; PubMed Central PMCID: PMC3057506.
3: Chapuis N, Lacombe C, Tamburini J, Bouscary D, Mayeux P. Insulin receptor A and IGF-1R in AML - Letter. Cancer Res. 2010 Sep 1;70(17):7010; author reply 7010. doi: 10.1158/0008-5472.CAN-10-0136. Epub 2010 Aug 10. PubMed PMID: 20699367.
4: Hewish M, Chau I, Cunningham D. Insulin-like growth factor 1 receptor targeted therapeutics: novel compounds and novel treatment strategies for cancer medicine. Recent Pat Anticancer Drug Discov. 2009 Jan;4(1):54-72. Review. PubMed PMID: 19149688.
5: Xu Y, Wang GS, Sun W, Yang XH, Xu LB. [Progress in the studies on small molecule IGF-1R inhibitors]. Yao Xue Xue Bao. 2008 Oct;43(10):979-84. Review. Chinese. PubMed PMID: 19127859.
6: Haluska P, Carboni JM, TenEyck C, Attar RM, Hou X, Yu C, Sagar M, Wong TW, Gottardis MM, Erlichman C. HER receptor signaling confers resistance to the insulin-like growth factor-I receptor inhibitor, BMS-536924. Mol Cancer Ther. 2008 Sep;7(9):2589-98. doi: 10.1158/1535-7163.MCT-08-0493. Epub 2008 Sep 2. PubMed PMID: 18765823; PubMed Central PMCID: PMC2614316.
7: Haluska P, Carboni JM, Loegering DA, Lee FY, Wittman M, Saulnier MG, Frennesson DB, Kalli KR, Conover CA, Attar RM, Kaufmann SH, Gottardis M, Erlichman C. In vitro and in vivo antitumor effects of the dual insulin-like growth factor-I/insulin receptor inhibitor, BMS-554417. Cancer Res. 2006 Jan 1;66(1):362-71. PubMed PMID: 16397250.