RP-3500(Synonyms: ATR inhibitor 4)

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上海金畔生物科技有限公司为生命科学和医药研发人员提供生物活性分子抑制剂、激动剂、特异性抑制剂、化合物库、重组蛋白，专注于信号通路和疾病研究领域。

RP-3500 (Synonyms: ATR inhibitor 4)

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。

RP-3500(Synonyms: ATR inhibitor 4)

RP-3500 Chemical Structure

CAS No. : 2417489-10-0

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5 mg ￥6800 询问价格 & 货期
10 mg ￥11000 询问价格 & 货期

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生物活性

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].

IC50 & Target[1]

ATR

 

ATM

>30 μM (IC50)

mTOR

120 nM (IC50)

体外研究
(In Vitro)

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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Western Blot Analysis[1]

Cell Line: LoVo and CW-2 human colon cancer cell lines
Concentration: 1 μM
Incubation Time: 1, 2, 4, 6, 8, 16, 24 hours
Result: Inhibited CHK1(Ser345) phosphorylation from 1 to 3 hours. Starting at 4 hours, CHK1(Ser345) became re-phosphorylated as DNA-PKcs became activated in treated cells, along with its substrates KAP1 and H2AX.

体内研究
(In Vivo)

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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: Female mice (6-8 weeks old) bearing LoVo xenografts[1]
Dosage: 3, 7, 15 mg/kg (0.5% methylcellulose/0.02% SDS vehicle)
Administration: Orally; once daily for 18 days
Result: Produced dose-dependent tumor growth inhibition with a minimum effective dose (MED) of 7 mg/kg.
The maximum tolerated dose (MTD) was 10 mg/kg once daily on a continuous dosing schedule.

分子量

410.47

Formula

C21H26N6O3
CAS 号

2417489-10-0
运输条件

Room temperature in continental US; may vary elsewhere.
储存方式

Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献

  • [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

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