Prexasertib dihydrochloride

SKU: orb1226712

Description

A potent, selective, ATP-competitive inhibitor of CHK1 with Ki of 0.9 nM; potently abrogates the G2-M checkpoint activated by doxorubicin in p53-deficient HeLa cells with EC50 of 9 nM; causes replication catastrophe in vitro and in vivo; shows significant tumor growth inhibition in xenograft tumor models.Lung Cancer Phase 2 Clinical.

Key Properties

• CAS Number: 1234015-54-3
• MW: 438.311
• Purity: >98% (HPLC)
• Formula: C₁₈H₂₁Cl₂N₇O₂
• SMILES: COC1=C(C(=CC=C1)OCCCN)C2=CC(=NN2)NC3=NC=C(N=C3)C#N.Cl.Cl
• Target: Chk
• Solubility: DMSO: ≥ 32 mg/mL

Bioactivity

• In Vivo:
  Animal model: Female CD-1 nu-/nu-mice (26-28 g) with Calu-6 cells. Dosage: 1, 3.3, or 10 mg/kg. Administration: SC; twice daily for 3 days, rest 4 days; for three cycles. Result: Caused statistically significant tumor growth inhibition (up to 72.3%). Animal model: Female CD-1 nu-/nu-mice (26-28 g) with Calu-6 cells. Dosage: 15 mg/kg (Pharmacokinetic Analysis). Administration: SC (200 μL). Result: CHK1 was 7 ng/mL at 12 hours and 3 ng/mL by 24 hours in plasma exposures. Phosphorylation of both H2AX (S139) and RPA2 (S4/S8) was detectable at 4 hours, showing the rapid occurrence of DNA damage.
• In Vitro:
  Cell Cycle Analysis Cell line: HeLa cells. Concentration: 33, 100 nM. Incubation time: For 7 hours. Result: Had an IC50 of 37 nM and resulted in the G2-M population received DNA damage during S-phase but continued to progress through the cell cycle into an early mitosis. Western blot analysis. Cell line: HT-29 cells. Concentration: 8, 16, 31, 63, 125, 250 nM. Incubation time: Pre-treated for 15 minutes. Result: Inhibited CHK1 autophosphorylation (S296) and CHK2 autophosphorylation (S516) (IC50 of less than 31 nM) in HT-29 cells.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

LY-2606368 dihydrochloride | LY 2606368 dihydrochloride

Quick Database Links

Gene Symbol

Chk