AZD-7762

SKU: orb1223833

Description

AZD-7762 (AZD7762) is a potent and selective inhibitor of Chk1/2 with IC50 of 5 nM; shows less potent against CAM, Yes, Fyn, Lyn, Hck and Lck; enhances the radiosensitivity of mutated p53 tumor cell lines and HT29 xenografts.Solid Tumors,Phase 1 Discontinued(In Vitro):AZD-7762 (AZD7762) is an equally potent inhibitor of Chk1 and Chk2 in vitro. AZD-7762 potently inhibits Chk1 and Chk2, abrogates DNA damage-induced S and G2 checkpoints, enhances the efficacy of NSC 613327 and SKF 104864A, and modulates downstream checkpoint pathway proteins. AZD-7762 potently inhibits Chk1 phosphorylation of a cdc25C peptide with an IC50 of 5 nM as measured by a scintillation proximity assay. The Ki for AZD-7762 is determined to be 3.6 nM. Kinetic characterization suggests that AZD-7762 binds in the ATP-binding site of Chk1 and is thought to compete directly for ATP binding in a reversible manner. AZD-7762 is shown to abrogate the G2 arrest induced by Camptothecin with an average EC50 of 10 nM (n=12) and maximal abrogation in the range of 100 nM.\n(In Vivo):In the rat H460-DNp53 xenograft study, AZD-7762 (AZD7762) potentiates the antitumor activity of NSC 613327 in a dose-dependent manner by a decrease in %T/C with increasing dose (48% and 32%, 10 and 20 mg/kg AZD-7762, respectively). In the mouse xenograft study in combination with CPT-11, SW620 established tumors are treated with vehicle, CPT-11 alone, AZD-7762 alone, or AZD-7762 in combination with CPT-11. AZD-7762 dosed alone shows insignificant antitumor activity, whereas CPT-11 alone displays striking and significant activity (%T/C with increasing dose is 9 and 1, respectively ). In combination with AZD-7762, %T/C increases significantly to -66% and -67%, respectively. AZD7762 combination with CX-5461 induces cancer cell death of Tp53-null (Tp53-/-) Eμ-Myc lymphoma cells in vitro and in vivo.

Key Properties

• CAS Number: 860352-01-8
• MW: 362.4218
• Purity: >98% (HPLC)
• Formula: C₁₇H₁₉FN₄O₂S
• SMILES: O=C(C1=C(NC(N)=O)C=C(C2=CC=CC(F)=C2)S1)N[C@@H]3CNCCC3
• Target: Chk
• Solubility: 10 mM in DMSO

Bioactivity

• In Vivo:
  In the rat H460-DNp53 xenograft study, AZD-7762 (AZD7762) potentiates the antitumor activity of NSC 613327 in a dose-dependent manner by a decrease in %T/C with increasing dose (48% and 32%, 10 and 20 mg/kg AZD-7762, respectively). In the mouse xenograft study in combination with CPT-11, SW620 established tumors are treated with vehicle, CPT-11 alone, AZD-7762 alone, or AZD-7762 in combination with CPT-11. AZD-7762 dosed alone shows insignificant antitumor activity, whereas CPT-11 alone displays striking and significant activity (%T/C with increasing dose is 9 and 1, respectively). In combination with AZD-7762, %T/C increases significantly to-66% and-67%, respectively. AZD7762 combination with CX-5461 induces cancer cell death of Tp53-null (Tp53-/-) Eμ-Myc lymphoma cells in vitro and In vivo.
• In Vitro:
  AZD-7762 (AZD7762) is an equally potent inhibitor of Chk1 and Chk2 in vitro. AZD-7762 potently inhibits Chk1 and Chk2, abrogates DNA damage-induced S and G2 checkpoints, enhances the efficacy of NSC 613327 and SKF 104864A, and modulates downstream checkpoint pathway proteins. AZD-7762 potently inhibits Chk1 phosphorylation of a cdc25C peptide with an IC50 of 5 nM as measured by a scintillation proximity assay. The Ki for AZD-7762 is determined to be 3.6 nM. Kinetic characterization suggests that AZD-7762 binds in the ATP-binding site of Chk1 and is thought to compete directly for ATP binding in a reversible manner. AZD-7762 is shown to abrogate the G2 arrest induced by Camptothecin with an average EC50 of 10 nM (n=12) and maximal abrogation in the range of 100 nM.

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

AZD7762 | AZD 7762

Quick Database Links

Gene Symbol

Chk