Neratinib

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

一种有效、高选择性、不可逆的 HER2 和 EGFR 抑制剂，在无细胞测定中 IC50 分别为 59 nM 和 92 nM。

A potent, highly selective, irreversible HER2 and EGFR inhibitor with IC50 of 59 nM and 92 nM in cell-free assays; weakly inhibits KDR and Src (IC50=0.8 and 1.4 uM), no significant inhibition to Akt, CDK1/2/4, IKK-2, MK-2, PDK1, c-Raf and c-Met; inhibits downstream signal transduction events and cell cycle regulatory pathways, leads to arrest at the G(1)-S phase transition, decreases cell proliferation; active in HER-2- and EGFR-dependent tumor xenograft models, orally bioavailable.Breast Cancer Approved.

Cell Proliferation Assay Cell Line:3T3, 3T3/neu, SK-Br-3, BT 474, A431, MDA-MB-435 and SW620 Concentration:0.5 ng/mL–5 μg/mL Incubation Time:2 days (6 days for BT474)Result:Inhibited cell proliferation with IC50 values of 700 ± 78, 3 ± 0.14, 2 ± 0.18, 2 ± 0.06, 81± 9, 960 ± 165 and 690 ± 84 nM against 3T3, 3T3/neu, SK-Br-3, BT 474, A431, MDA-MB-435 and SW620 cells, respectively.Western Blot Analysis Cell Line:BT474 or A431 cells Concentration:0, 2, 10, 50, 100 and 200 nM Incubation Time:3 h Result:Decreased ligand-independent receptor phosphorylation by 50% (IC50) at 5 nM in BT474 cells, repressed EGF-dependent phosphorylation of EGFR in A431 cells at a comparable dose (IC50 = 3 nM). Effectively repressed phosphorylation of MAPK and Akt in BT474 cells.Cell Cycle Analysis Cell Line:BT474 Concentration:0–2 nM Incubation Time:12–16 h Result:Blocked cell cycle progression, causing a G1-S arrest, a 50% decrease in the number of cells in the S (DNA synthesis) phase of the cell cycle was observed at a concentration of 2 nM.

Animal Model:Female athymic (nude) mice, tumor xenograftDosage:10, 20, 40, 60 or 80 mg/kg/day Administration:Gavage, 42 days Result:Reduced tumor growth in a dose-dependent manner in 3T3/neu, BT474, SK-OV-3 and A431 xenografts, but was o inactive in xenografts of MX-1 and MCF-7. Inhibited phosphorylation of HER-2 in BT474 xenografts.

HKI-272 | HKI272 | HKI 272

Angiogenesis

EGFR

EGFR|HER2|PDK1|Src|VEGFR2?(KDR)

Cancer

Breast Cancer

698387-09-6

557.0427

C30H29ClN6O3

>98% (HPLC)

DMSO: 6.4 mg/mL (Need ultrasonic)

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

2-Butenamide, N-[4-[[3-chloro-4-(2-pyridinylmethoxy)phenyl]amino]-3-cyano-7-ethoxy-6-quinolinyl]-4-(dimethylamino)-, (2E)-

(-20℃)

With Ice Pack

≥ 2 years