AZD0364

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

AZD0364 (AZD-0364) 是一种有效的、选择性的、口服活性的 ERK1/2 抑制剂，用于治疗 NSCLC。

AZD0364 (AZD-0364) is a potent, selective, orally active ERK1/2 inhibitor for treatment of NSCLC.

Tizaterkib is measured in the ERK2 mass spectrometry and A375 phospho-p90RSK assays with IC50s of 0.6 nM and 5.7 nM, respectively. Tizaterkib can inhibit the growth of a panel of cancer cell lines (A549, H2122, H2009, and Calu6 cell lines) with KRAS mutations as a monotherapy and this effect is synergistically enhanced by treatment with Selumetinib.

Tumor growth inhibition by Tizaterkib ethanesulfonic acid (Example 18a) in combination with MEK inhibitor Selumetinib is measured. Studies are performed in the A549 xenograft model. Selumetinib is dosed twice daily (BiD) 8 hours apart and Tizaterkib ethanesulfonic acid is dosed once daily (QD) 4 hours after the first Selumetinib dose. Both compounds are dosed continuously for 3 weeks. Both vehicles are dosed in the vehicle group. Both Selumetinib and Tizaterkib ethanesulfonic acid reduce tumor growth relative to vehicle only control. The combination of Selumetinib and Tizaterkib ethanesulfonic acid results in a reduction in tumor growth.

AZD-0364

MAPK/ERK Signaling

ERK

ERK

Cancer

——

2097416-76-5

494.507

C24H24F2N8O2

>98% (HPLC)

DMSO : ≥ 100 mg/mL 202.22 mM

CC1=CN=C(N=C1C2=CN3CC(N(C(=O)C3=N2)CC4=CC(=C(C=C4)F)F)COC)NC5=CC=NN5C

(6R)-7-(3,4-Difluorobenzyl)-6-(methoxymethyl)-2-{5-methyl-2-[(1-methyl-1H-pyrazol-5-yl)amino]-4-pyrimidinyl}-6,7-dihydroimidazo[1,2-a]pyrazin-8(5H)-one

(-20℃)

With Ice Pack

≥ 2 years