| Identification | Back Directory | [Name]
camonsertib | [CAS]
2417489-10-0 | [Synonyms]
RP-3500
camonsertib
RP-3500 (Synonyms: ATR inhibitor 4)
8-Oxabicyclo[3.2.1]octan-3-ol, 3-[6-[(3R)-3-methyl-4-morpholinyl]-1-(1H-pyrazol-3-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl]-, (3-endo)- | [Molecular Formula]
C21H26N6O3 | [MOL File]
2417489-10-0.mol | [Molecular Weight]
410.48 |
| Chemical Properties | Back Directory | [Boiling point ]
666.8±55.0 °C(Predicted) | [density ]
1.61±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [form ]
Solid | [pka]
10.79±0.10(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Uses]
Camonsertib (RP-3500) is an orally active, selective ATR kinase inhibitor (ATRi) with an IC50 of 1.00 nM in biochemical assays. Camonsertib shows 30-fold selectivity for ATR over mTOR (IC50=120 nM) and >2,000-fold selectivity over ATM, DNA-PK, and PI3Kα kinases. Camonsertib has potent antitumor activity[1]. | [in vivo]
Camonsertib (RP-3500; 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].
Camonsertib (5, 10 mg/kg; Orally; once daily) produces statistically significant tumor growth inhibition in the CW-2 colon xenograft model[1].
Camonsertib (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].
Camonsertib 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].
Camonsertib (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].
| 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.
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| [IC 50]
ATR; ATM: >30 μM (IC50); mTOR: 120 nM (IC50) | [storage]
Store at -20°C | [References]
[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 DOI:10.1158/1535-7163.MCT-21-0615 |
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