[CAS NO. 1196541-47-5] GDC-0575
PRODUCTS SPECIFICATIONS [1196541-47-5]
DESCRIPTION [1196541-47-5]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 378.27 |
| Molecular Formula | C16H20BrN5O |
| SMILES | O=C(C1CC1)NC2=CNC3=NC=C(Br)C(N4C[C@H](N)CCC4)=C32 |
4 Publications Citing Use of MCE
Summary
GDC-0575 (ARRY-575, RG7741) is a highly-selective oral small-molecule Chk1 inhibitor with an IC 50 of 1.2 nM.
IC50 & Target
1.2 nM (Chk1) [1]
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 [1] . 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 [2] . CHK1 inhibitor GDC-0575 in combination with AraC enhances the killing of primary acute myeloid leukemia cells ex vivo by inducing apoptosis [3] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
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 [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT01564251 | Genentech, Inc. |
Lymphoma, Solid Tumor
|
March 23, 2012 | Phase 1 |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : 100 mg/mL ( 264.36 mM ; Need ultrasonic)
H 2 O : < 0.1 mg/mL (insoluble)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.6436 mL | 13.2181 mL | 26.4361 mL |
| 5 mM | 0.5287 mL | 2.6436 mL | 5.2872 mL |
| 10 mM | 0.2644 mL | 1.3218 mL | 2.6436 mL |
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1.
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2.
Add each solvent one by one: 10% DMSO >> 90% (20% SBE-β-CD in saline)
Solubility: ≥ 2.5 mg/mL (6.61 mM); Clear solution
References
- [1] Oo ZY, et al. Endogenous Replication Stress Marks Melanomas Sensitive to CHEK1 Inhibitors In Vivo. Clin Cancer Res. 2018 Mar 13. doi: 10.1158/1078-0432.CCR-17-2701.
- [2] Laroche-Clary A, et al. CHK1 inhibition in soft-tissue sarcomas: biological and clinical implications. Ann Oncol. 2018 Apr 1;29(4):1023-1029.
- [3] Di Tullio A, et al. The combination of CHK1 inhibitor with G-CSF overrides cytarabine resistance in human acute myeloid leukemia. Nat Commun. 2017 Nov 22;8(1):1679.