GDC-0575

SKU: orb1299941

Description

GDC-0575

Research Area

Cell Biology

Key Properties

• CAS Number: 1196541-47-5
• MW: 378.27
• Purity: 98.00%
• Formula: C₁₆H₂₀BrN₅O
• SMILES: N[C@@H]1CCCN(C1)c1c(Br)cnc2[nH]cc(NC(=O)C3CC3)c12
• Target: Chk
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (5.29 mM);DMSO:50 mg/mL (132.18 mM)

Bioactivity

• Target IC50:
  Chk1:1.2 nM
• In Vivo:
  CHK1 inhibitor (CHK1i) GDC-0575 enhances AraC-mediated killing of AML cells both in vitro and in vivo, thus abrogating any potential chemoresistance mechanisms involving DNA repair. Importantly, this combination of drugs does not affect normal long-term hematopoietic stem/progenitors.
• In Vitro:
  GDC-0575 demonstrates markedly higher efficacy in inducing DNA damage, replication stress, and cell death compared to V158411, LY2603618, and MK-8776 in a panel of melanoma cell lines.
• Animal Research:
  For in vivo experiments, aliquots of GDC-0575 (10 mg/mL) were stored at 20℃and diluted in 100 mM sodium citrate buffer immediately prior to each experiment. GDC-0575 was used at 1.8 mg/ml for female mice (~25 g) and 2.6 mg/ml for male mice (~35 g) via oral gavage (final concentration 7.5 mg/kg). For in vitro experiments, aliquots of GDC-0575 (100 μM) were stored at 20 ℃ and used at a final concentration of 100 nM. AraC (Cytosine β-D-arabinofuranoside C1768, Sigma) was used at 10 mg/kg (commonly used in clinical practice) for in vivo and at 100 nM and 500 nM for in vitro experiments. For in vivo experiments, toxicity of GDC-0575 was assessed in non-engrafted NSG mice using a range of concentrations of GDC-0575 in combination with AraC. 7.5 mg/kg GDC-0575 was the highest concentration to have no significant or lasting adverse effects in mice. Similarly, for in vitro experiments, 100 nM GDC-0575 in combination with 500 nM AraC was the highest concentration non-cytotoxic to MS5 stoma cell. ATR inhibitor was used at a final concentration of 0.5 μM.

Storage & Handling

• Storage: 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

ARRY 575, ARRY575, ARRY-575, Chk1, Checkpoint Kinase (Chk), inhibit, Inhibitor, GDC0575, GDC-0575, GDC 0575, RG 7741, RG7741, RG-7741

Compound Identifiers

PubChem CID

46917793