RP-3500 (ATR inhibitor 4) 是一种口服有效的，选择性 ATR 激酶抑制剂 (ATRi)，在生化试验中的 IC50 为 1.00 nM。RP-3500 对 ATR 的选择性是 mTOR 的 30 倍 (IC50=120 nM)，是 ATM、DNA-PK 和 PI3Kα 激酶的 >2,000 倍。RP-3500 具有有效的抗肿瘤活性。
货号:ajcx37304
CAS:2417489-10-0
分子式:C21H26N6O3
分子量：410.47
溶解度:N/A
纯度：98%
存储：Store at -20°C
库存：现货

Background:

RP-3500 (ATR inhibitor 4) is an orally active, selective ATR kinase inhibitor (ATRi) with an IC50 of 1.00 nM in biochemical assays. RP-3500 shows 30-fold selectivity for ATR over mTOR (IC50=120 nM) and >2,000-fold selectivity over ATM, DNA-PK, and PI3Kα kinases. RP-3500 has potent antitumor activity[1].

RP-3500 (ATR inhibitor 4; 1 μM; 1-24 hours) inhibits CHK1(Ser345) phosphorylation from 1 to 3 hours[1]. RP-3500 inhibits Gemcitabine stimulated ATR phosphorylation of its substrate pCHK1(Ser345) with an IC50 of 0.33 nM in a LoVo cell-based assay[1].

RP-3500 (ATR inhibitor 4; 3, 7, 15 mg/kg; Orally; once daily for 18 days) produces dose-dependent tumor growth inhibition with a minimum effective dose (MED) of 7 mg/kg in LoVo xenografts[1]. RP-3500 (5, 10 mg/kg; Orally; once daily) produces statistically significant tumor growth inhibition in the CW-2 colon xenograft model[1]. RP-3500 (7 mg/kg; for 7 days) results in 8.1- and 2.7-fold inductions of KAP1 and DNA-PKcs phosphorylation in mice bearing LoVo tumors[1]. RP-3500 has a more profound anti-tumor effect occurred at higher doses on the 3 days on/4 days off (30 mg/kg) and 5 days on/2 days off (25 mg/kg) schedules compared with consecutive daily administrations (10 mg/kg) at a lower dose for 14 days[1]. RP-3500 (15mg/kg) combined PARPi Olaparib (80mg/kg; both agents days 1-3 on/4 days off) or sequential (PARPi for 3 days followed by RP-3500 for 3 days then 1 day off) schedules produces greater antiTumor effects compared with sequential administration without affecting tolerability[1].

[1]. Anne Roulston, et al. RP-3500: A Novel, Potent and Selective ATR Inhibitor that is Effective in Preclinical Models as a Monotherapy and in Combination with PARP Inhibitors. Mol Cancer Ther