AC480 (BMS-599626) is a selective, highly potent HER1 and HER2 inhibitor with IC50 of 20 nM and 30 nM, respectively. The effect is about 8 times stronger than HER4, and more than 100 times stronger than VEGFR2, c-Kit, Lck, MET, etc. Phase 1.

 

Brand: BCM

 

Target: HER1:20 nM, HER2:30 nM, HER4:190 nM

 

In Vitro: BMS-599626 selectively inhibits the enzymatic activity of recombinant HER1 and HER2 kinases with IC50 of 20 nM and 30 nM, respectively. In addition, BMS-599626 also inhibited the related receptor HER4, but the inhibitory effect was low (IC50 was 190 nM). BMS-599626 is defined as an ATP competitive inhibitor of HER1 and an ATP non-competitive inhibitor of HER2 with Ki of 2 nM and 5 nM, respectively. BMS-599626 inhibits the proliferation of tumor cells expressing high levels of HER1 and/or HER2, Including Sal2, BT474, N87, KPL-4, HCC202, HCC1954, HCC1419, AU565, ZR-75-30, MDA-MB-175, GEO, and PC9 cells, IC50 were 0.24 mu M, 0.31 mu M, 0.45 mu M, 0.38 mu M, 0.94 mu M, 0.34 mu M, 0.75 mu M, 0.63 mu M, 0.51 mu M, 0.84 mu M, 0.90 mu mu M and 0.34 M. BMS-599626 does not significantly inhibit the proliferation of ovarian tumor cell lines A2780 and MRC5 fibroblasts that do not express HER1 or HER2. Recent studies have shown that BMS-599626 significantly enhances the radiosensitivity of EGFR - and HER2-expressing HN-5 cells by promoting cycle redistribution and inhibiting DNA repair.

 

pKa: 7.27±0.46(Predicted)

 

Solubility: Soluble in DMSO; soluble in Ethanol. Insoluble in Water.

 

GHS: GHS07

 

Isomeric SMILES: CC1=C2C(=NC=NN2C=C1NC(=O)OC[C@@H]3COCCN3)NC4=CC5=C(C=C4)N(N=C5)CC6=CC(=CC=C6)F  

 

InChIKey: LUJZZYWHBDHDQX-QFIPXVFZSA-N  

 

InChI: InChI=1S/C27H27FN8O3/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)/t22-/m0/s1

 

Attribute
[Chem Name]	[(3S)-morpholin-3-yl]methyl N-[4-[[1-[(3-fluorophenyl)methyl]indazol-5-yl]amino]-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl]carbamate
[Synonym]	AC480; BMS-599626
[CAS No.]	714971-09-2
[MDL No.]	MFCD10565678
[Formula]	C27H27FN8O3
[Molecular]	530.55
[Form]	Solid Powder
[Storage]	Sealed in dry, 2-8°C

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