AC480 HCl

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WARNING: This product is for research use only, not for human or veterinary use.

Description:AC480, also known as BMS-599626, is an orally bioavailable inhibitor of the HER1, HER2 and HER4 tyrosine kinases (IC50 =22, 32 and 190 nM, respectively) with potential antineoplastic activity. BMS-599626 inhibits human epidermal growth factor receptors (HER) HER1, HER2 and HER4, thereby inhibiting the proliferation of tumor cells that overexpress these receptors.

Price and Availability

AC480 HCl, purity > 98%, is in stock. The same day shipping out after order is received.

Chemical Structure

Theoretical Analysis

MedKoo Cat#: 200078Name: AC480 HClCAS#: 873837-23-1 (HCl)Chemical Formula: C27H28ClFN8O3Exact Mass: 566.2Molecular Weight: 567.02Elemental Analysis: C, 57.19; H, 4.98; Cl, 6.25; F, 3.35; N, 19.76; O, 8.46

Related CAS #:873837-23-1 (HCl)714971-09-2 (free base)

Synonym:AC480; AC-480; AC 480 HCl; AC 480 hydrochloride; BMS599626; BMS-599626; BMS 599626; BMS599626 HCl; BMS599626 hydrochloride.

IUPAC/Chemical Name:(S)-morpholin-3-ylmethyl (4-((1-(3-fluorobenzyl)-1H-indazol-5-yl)amino)-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl)carbamate hydrochloride

InChi Key:COUSSRGSHIJMMN-FTBISJDPSA-N

InChi Code:InChI=1S/C27H27FN8O3.ClH/c1-17-23(34-27(37)39-15-22-14-38-8-7-29-22)13-36-25(17)26(30-16-32-36)33-21-5-6-24-19(10-21)11-31-35(24)12-18-3-2-4-20(28)9-18;/h2-6,9-11,13,16,22,29H,7-8,12,14-15H2,1H3,(H,34,37)(H,30,32,33);1H/t22-;/m0./s1

SMILES Code:O=C(OC[C@H]1NCCOC1)NC2=CN3N=CN=C(NC4=CC5=C(N(CC6=CC=CC(F)=C6)N=C5)C=C4)C3=C2C.[H]Cl

Technical Data

References

1: Soria JC, Cortes J, Massard C, Armand JP, DeAndreis D, Ropert S, Lopez E, Catteau A, James J, Marier JF, Beliveau M,Martell RE, Baselga J. Phase I safety, pharmacokinetic andpharmacodynamic trial of BMS-599626 (AC480), an oral pan-HER receptortyrosine kinase inhibitor, in patients with advanced solid tumors. AnnOncol. 2012 Feb;23(2):463-71. doi: 10.1093/annonc/mdr137. Epub 2011 May16. PubMed PMID: 21576284.

2: Torres MA, Raju U, Molkentine D, Riesterer O, Milas L, Ang KK. AC480,formerly BMS-599626, a pan Her inhibitor, enhances radiosensitivity andradioresponse of head and neck squamous cell carcinoma cells in vitroand in vivo. Invest New Drugs. 2011 Aug;29(4):554-61. doi:10.1007/s10637-010-9389-3. Epub 2010 Feb 2. PubMed PMID: 20119866.

3: Gavai AV, Fink BE, Fairfax DJ, Martin GS, Rossiter LM, Holst CL, KimSH, Leavitt KJ, Mastalerz H, Han WC, Norris D, Goyal B, Swaminathan S,Patel B, Mathur A, Vyas DM, Tokarski JS, Yu C, Oppenheimer S, Zhang H,Marathe P, Fargnoli J, Lee FY, Wong TW, Vite GD. Discovery andpreclinical evaluation of[4-[[1-(3-fluorophenyl)methyl]-1H-indazol-5-ylamino]-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl]carbamic acid, (3S)-3-morpholinylmethyl ester(BMS-599626), a selective and orally efficacious inhibitor of humanepidermal growth factor receptor 1 and 2 kinases. J Med Chem. 2009 Nov12;52(21):6527-30. doi: 10.1021/jm9010065. PubMed PMID: 19821562.

4: Haluska P, Carboni JM, TenEyck C, Attar RM, Hou X, Yu C, Sagar M,Wong TW, Gottardis MM, Erlichman C. HER receptor signaling confersresistance 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.

5: Wong TW, Lee FY, Yu C, Luo FR, Oppenheimer S, Zhang H, Smykla RA,Mastalerz H, Fink BE, Hunt JT, Gavai AV, Vite GD. Preclinical antitumoractivity of BMS-599626, a pan-HER kinase inhibitor that inhibitsHER1/HER2 homodimer and heterodimer signaling. Clin Cancer Res. 2006 Oct15;12(20 Pt 1):6186-93. PubMed PMID: 17062696.

6: Albanell J, Gascón P. Small molecules with EGFR-TK inhibitoractivity. Curr Drug Targets. 2005 May;6(3):259-74. Review. PubMed PMID:15857287.