468741-42-6|BMS-554417|(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|-范德生物科技公司

BMS-554417

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names：
(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
CAS号：
468741-42-6
MDL Number：
MF(分子式)： C28H30ClN7O2 MW(分子量)： 532.04
EINECS: Reaxys Number:
Pubchem ID: Brand:BIOFOUNT

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中文别名	BMS-554417
英文别名	BMS554417; BMS 554417; BMS-554417.
CAS号	468741-42-6
SMILES	N#CCCN1CCN(C2=CC(C)=C3NC(C4=C(NC[C@H](C5=CC=CC(Cl)=C5)O)C=CNC4=O)=NC3=C2)CC1
Inchi	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
InchiKey	VVIPLSCLYCWUQT-XMMPIXPASA-N
分子式 Formula	C28H30ClN7O2
分子量 Molecular Weight	532.04
闪点 FP
熔点 Melting point
沸点 Boiling point
Polarizability极化度
密度 Density
蒸汽压 Vapor Pressure
溶解度Solubility
性状	Solid powder
储藏条件 Storage conditions	Dry, dark and store at 0-4℃ for short term (days to weeks) or -20℃ for long term (Store correctly 2-3years).

产品说明	BMS-554417(CAS:468741-42-6 ):仅限应用于工业或者科学研究过程中非医疗目的，不应用于人类或动物的临床诊断以及治过程疗，该产品非药用，非食用。
Introduction	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.
Application1
Application2
Application3

警示图
危险性	Warning
危险性警示
安全声明
安全防护
备注

[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.

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