GDC-0575

SKU: orb1226825

Description

GDC-0575 (ARRY-575, RG-7741) is a potent, selective and orally bioavailable Chk1 inhibitor with IC50 of 1.2 nM; enhances the killing of primary AML cells ex vivo by inducing apoptosis combined with AraC, blocks the activation of CHK1 induced by AraC via decrease in the level of Tyr15-phosphorylated CDK2 at 100 nM in AML cells.Blood Cancer Phase 1 Clinical(In Vitro):GDC-0575 is significantly more potent in promoting DNA damage, replication stress and cell death than V158411, LY2603618, and MK-8776 in a panel of melanoma cell lines. GDC-0575 abrogates DNA damage-induced S and G2–M checkpoints, exacerbates DNA double-strand breaks and induces apoptosis in STS cells. GDC-0575 has a synergistic or additive effect together with gemcitabine. CHK1 inhibitor GDC-0575 in combination with AraC enhances the killing of primary acute myeloid leukemia cells ex vivo by inducing apoptosis.(In Vivo):GDC-0575 is active at 25 mg/kg as a single agent, but the efficacy is improved at the higher drug dose. GDC-0575 effectively blocks tumor growth in the D20 and C002 xenografts, and the effect is maintained for at least 10 days after the final dose is administered.

Key Properties

• CAS Number: 1196541-47-5
• MW: 377.286
• Purity: >98% (HPLC)
• Formula: C₁₇H₂₁BrN₄O
• SMILES: C1CC(CN(C1)C2=C3C(=CNC3=NC=C2Br)NC(=O)C4CC4)N
• Target: Chk
• Solubility: DMSO : ≥ 50 mg/mL132.18 mM

Bioactivity

• In Vivo:
  GDC-0575 is active at 25 mg/kg as a single agent, but the efficacy is improved at the higher drug dose. GDC-0575 effectively blocks tumor growth in the D20 and C002 xenografts, and the effect is maintained for at least 10 days after the final dose is administered.
• In Vitro:
  GDC-0575 is significantly more potent in promoting DNA damage, replication stress and cell death than V158411, LY2603618, and MK-8776 in a panel of melanoma cell lines. GDC-0575 abrogates DNA damage-induced S and G2-M checkpoints, exacerbates DNA double-strand breaks and induces apoptosis in STS cells. GDC-0575 has a synergistic or additive effect together with gemcitabine. CHK1 inhibitor GDC-0575 in combination with AraC enhances the killing of primary acute myeloid leukemia cells ex vivo by inducing apoptosis.

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

ARRY-575 | RG-7741 | GDC0575

Quick Database Links

Gene Symbol

Chk