camonsertib

Product Namecamonsertib
CAS2417489-10-0
MFC21H26N6O3
MW410.47
EINECS
MOL File2417489-10-0.mol

Chemical Properties

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
InChIKey	YIHHYCIYAIVQKX-UHFFFAOYSA-N
SMILES	OC1(CC2CCC(O2)C1)C1C=C(N2CCOCC2C)N=C2N(C3=NNC=C3)N=CC=12

Usage And Synthesis

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.

IC 50

ATR; ATM: >30 μM (IC₅₀); mTOR: 120 nM (IC₅₀)

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

camonsertib Supplier

camonsertib manufacturers

Related Product Information

Send Inquriy