Neratinib is a highly selective HER2 and EGFR inhibitor with IC50 of 59 nM and 92 nM, respectively, in cell-free trials. KDR and Src were weakly inhibited, and Akt, CDK1/2/4, IKK-2, MK-2, PDK1, c-Raf and c-Met were not significantly inhibited. Phase 3.

 

Brand: BCM

 

Target: EGFR; HER

 

Signaling Pathways: Angiogenesis; JAK/STAT signaling; Tyrosine Kinase/Adaptors

 

In Vitro: Neratinib weakly inhibited tyrosine kinases KDR and Src with IC50 of 0.8 μM and 1.4 μM, respectively, which were 14 and 24 times weaker than HER-2. Neratinib acts on other silk-threonine kinases such as Akt, cyclin D1/cdk4, cyclin E/cdk2, cyclin B1/cdk1, IKK-2, MK-2, PDK1, c-Raf, and Tpl-2, And the tyrosine kinase c-Met is inactive. Neratinib selectively inhibited the proliferation of 3T3 cells transfected with HER-2 (3T3/neu), and also inhibited the proliferation of SK-Br-3 and BT474 cells with other HER-2- overexpression. With an IC50 of 2-3 nM, the effect was more than 230 times higher than that of untransfected 3T3 cells and MDA-MB-435 and SW620 cells with EGFR- and HER-2 negative. Neratinib also inhibited EGFR-dependent A431 cell proliferation with an IC50 of 81 nM. Neratinib acts on BT474 cells to reduce HER-2 receptor autophosphorylation with IC50 of 5 nM, and acts on A431 cells to reduce EGF-dependent EGFR phosphorylation with IC50 of 3 nM. Neratinib inhibits HER-2, resulting in the downstream MAPK and Akt pathways being inhibited with an IC50 of 2 nM, which is more effective than Trastuzumab. Neratinib acts on BT474 cells, inhibiting cyclin D1 expression and RB-sensitive gene product phosphorylation with an IC50 of 9 nM, resulting in the cell cycle stopping in the G1-S phase and ultimately reducing cell proliferation.

 

Melting Point: 185-187°C

 

Boiling Point: 757.0±60.0 °C(Predicted)

 

pKa: 12.37±0.43(Predicted)

 

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

 

GHS: GHS05

 

Isomeric SMILES: CCOC1=C(C=C2C(=C1)N=CC(=C2NC3=CC(=C(C=C3)OCC4=CC=CC=N4)Cl)C#N)NC(=O)/C=C/CN(C)C  

 

InChIKey: JWNPDZNEKVCWMY-VQHVLOKHSA-N  

 

InChI: InChI=1S/C30H29ClN6O3/c1-4-39-28-16-25-23(15-26(28)36-29(38)9-7-13-37(2)3)30(20(17-32)18-34-25)35-21-10-11-27(24(31)14-21)40-19-22-8-5-6-12-33-22/h5-12,14-16,18H,4,13,19H2,1-3H3,(H,34,35)(H,36,38)/b9-7+

 

Attribute
[Chem Name]	(E)-N-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]-3-cyano-7-ethoxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide
[Synonym]	Neratinib; HKI-272; HKI 272
[CAS No.]	698387-09-6
[EINECS]	811-237-1
[MDL No.]	MFCD09752958
[Formula]	C30H29ClN6O3
[Molecular]	557.04
[Form]	Off-white solid
[Storage]	Keep in dark place. Inert atmosphere. Store in freezer, under -20°C

Goods Tag