Camonsertib

SKU: orb1687955

Description

Camonsertib (RP-3500) is a highly selective ATR kinase inhibitor with an IC50 of 1 nM, showing 30-fold selectivity over mTOR and >2000-fold over related kinases. It has demonstrated potent antitumor activity in preclinical studies, supporting its investigation in cancer research involving DNA damage response pathways.

Research Area

Molecular Biology, Signal Transduction

Key Properties

• CAS Number: 2417489-10-0
• MW: 410.47
• Purity: 99.60%
• Formula: C₂₁H₂₆N₆O₃
• SMILES: C[C@@H]1COCCN1c1cc(c2cnn(-c3cc[nH]n3)c2n1)[C@@]1(O)C[C@@H]2CC[C@H](C1)O2
• Target: mTOR,ATM/ATR
• Solubility: DMSO:45 mg/mL (109.63 mM);10% DMSO+40% PEG300+5% Tween-80+45% Saline:1.5 mg/mL (3.65 mM)

Bioactivity

• Target IC50:
  ATR:1 nM|mTOR:120 nM
• In Vivo:
  METHODS: Patients received Camonsertib (RP-3500) at doses ranging from 5-200 mg once daily or 40 to 80 mg twice daily for 5 days/2 days off (5/2) or 3 days/4 days off ( 3/4), hematological parameters were assessed over a range of doses during treatment. RESULTS Early decrease in monocytes and reticulocytes on day 8 and further decrease in hemoglobin levels on day 15. METHODS: Camonsertib (RP-3500) was used to treat LoVo tumor xenografts in mice, orally administered once a day at a dose of 3/7/15 mg/kg for 17 days, and the effect on LoVo tumor xenografts in mice was observed. RESULTS Camonsertib (RP-3500) treatment of LoVo tumor xenografts in mice produced dose-dependent tumor growth inhibition, with a minimum effective dose (MED) of 7 mg/kg. METHODS: In the CW-2 colon xenograft model, Camonsertib (RP-3500) was administered at doses of 5 and 10 mg/kg to observe the effects on the growth of the mouse CW-2 colon xenograft model. RESULTS Treatment of xenograft mice with Camonsertib (RP-3500) produced statistically significant tumor growth inhibition.
• In Vitro:
  METHODS: Characterization of the DNA damage response (DDR) to Camonsertib (RP-3500)-mediated ATR inhibition in LoVo and CW-2 human colon cancer cell lines treated with 1 μmol/L RP-3500 for varying durations up to 24 hours. RESULTS Camonsertib (RP-3500) inhibits CHK1 (Ser345) phosphorylation 1-3 hours after initiation of treatment. METHODS: A biochemical assay for ATR/ATRIP inhibition was established using tagged human ATR and ATRIP purified from mammalian cells, with p53 (Ser15) as the phosphorylation substrate. RESULTS In a LoVo cell-based assay, Camonsertib (RP-3500) inhibited gemcitabine-stimulated phosphorylation of the ATR substrate pCHK1 (Ser345) with an IC50 of 0.33 nM.

Storage & Handling

• Storage: store at low temperature,keep away from direct sunlight | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Camonsertib, ATM, ATR, ATR inhibitor 4, RP 3500, RP3500, RP-3500

Compound Identifiers

PubChem CID

156487652