GDC-0575 dihydrochloride
Based on 6 publication(s) in Google Scholar
GDC-0575 dihydrochloride (ARRY-575 dihydrochloride) is an orally bioavailable CHK1 inhibitor, with an IC50 of 1.2 nM, and has antitumor activity.
For research use only. We do not sell to patients.
- Purity: 98.36%
- CAS No.: 1657014-42-0
- Formula: C16H22BrCl2N5O
- Molecular Weight:451.19
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Storage:
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Protocol
- Purity & Documentation
- References
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Help & FAQs
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Publications Citing Use of MedChemExpress (MCE) GDC-0575 dihydrochloride
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Biological Activity
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Chk1 1.2 nM (IC50) |
GDC-0575 dihydrochloride is a selective and orally bioavailable CHK1 inhibitor, with an IC50 of 1.2 nM. GDC-0575 (100 nM) suppressses CHK1 activation induced by AraC by decreasing the level of Tyr15-phosphorylated CDK2. GDC-0575 (100 nM) has no effect on the viability of AML cells, but significantly reduces cell viability and induces apoptosis in combination with AraC. In addition, GDC-0575 plus AraC shows no effect on normal hematopoietic stem and progenitor cells (HSPCs)[1]. GDC-0575 shows cytotoxic activity against most of 20 melanoma cell lines tested, but several cell lines grown as tumour sphere (TS) are relatively insensitive[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
| NCT Number | Sponsor | Condition | Start Date |
Phase
|
|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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CAS No. 1657014-42-0
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Appearance Solid
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Molecular Weight 451.19
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Formula C16H22BrCl2N5O
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Color Light yellow to yellow
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SMILES
O=C(C1CC1)NC2=CNC3=NC=C(Br)C(N4C[C@H](N)CCC4)=C32.[H]Cl.[H]Cl
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Synonyms
ARRY-575 dihydrochloride; RG7741 dihydrochloride
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Publications (6)
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Journal Impact Factor
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Most Recent
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Mol Cancer
2024 Apr 29;23(1):86. PMID: 38685067 -
Nat Commun
Treacle controls the nucleolar response to rDNA breaks via TOPBP1 recruitment and ATR activation. [Abstract]2020 Jan 8;11(1):123. PMID: 31913317 -
Neurotherapeutics
Chk1 Inhibition Ameliorates Alzheimer's Disease Pathogenesis and Cognitive Dysfunction Through CIP2A/PP2A Signaling. [Abstract]2022 Mar;19(2):570-591. PMID: 35286657 -
Mol Cancer Res
Inhibition of the ATR-CHK1 Pathway in Ewing Sarcoma Cells Causes DNA Damage and Apoptosis via the CDK2-Mediated Degradation of RRM2. [Abstract]2020 Jan;18(1):91-104. PMID: 31649026 -
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Solvent & Solubility
DMSO : 65 mg/mL (144.06 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
H2O : 25 mg/mL (55.41 mM; Need ultrasonic)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.17 mg/mL (4.81 mM); Clear solution
This protocol yields a clear solution of ≥ 2.17 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (21.7 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.17 mg/mL (4.81 mM); Clear solution
This protocol yields a clear solution of ≥ 2.17 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (21.7 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
For the following dissolution methods, please prepare the working solution directly:
It is recommended to prepare fresh solutions and use them promptly within a short period of time.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: PBS
Solubility: 10 mg/mL (22.16 mM); Clear solution; Need ultrasonic
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Working solution concentration: 0.22 mg/mL
This product has good water solubility, please refer to the measured solubility data in water/PBS/Saline for details.
Protocol
For co-culture experiments, 2 days before initiating the co-culture, feeder cells are plated onto type-I collagen-coated 96-well or 6-well plates and allowed to reach confluence. One day before starting co-culture, they are irradiated at 6.8 Gy and the culture media exchanged. On day 0 of the co-culture, AmL cells are plated at 2 × 105 cells/mL using the correspondent AmL medium. Cells are cultured at 37°C in 5% CO2-humidified incubators at indicated oxygen concentrations. For short-term culture (STC), cells are kept for 1 week in hypoxia (5% O2) with the indicated drugs: 500 nM AraC and/or 100 nM GDC-0575[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Mice[1]
NSG mice are injected intravenously with 1 × 105-106 cells of AmL and 1-3 × 105 cells of hCB CD34+/hBM CD34+. After demonstrating AmL engraftment at 9-11 weeks through FACS analysis of tibia bone marrow aspiration, mice are treated accordingly to proper 7-day treatment regimen with daily 10 mg/kg AraC via subcutaneous injection, 7.5 mg/kg GDC-0575 suspension administered via oral gavage on every other day schedule, and/or 300 μg/kg G-CSF administered daily for 5 days via intraperitoneal injection. One week after the final dosing, mice are killed by cervical dislocation. The femurs, tibias, and pelvis are dissected and flushed with PBS. Red blood cells are lyzed via ammonium chloride. Cells are stained with human-specific FITC-conjugated anti-CD19, PE-conjugated anti-CD33, PE-Cy7-conjugated anti-CD45, and PERCP-conjugated anti-murine CD45 antibodies. Dead cells and debris are excluded via DAPI staining. A BD LSR II flow cytometer is used for analysis. Flow cytometry analysis is performed with FlowJo software. More than 100,000 DAPI-negative events are collected. Engraftment of AmL is said to be present if a single population of mCD45-hCD45+CD33+CD19- cells is present without accompanying mCD45-hCD45+CD33−CD19+cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Purity & Documentation
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Data Sheet (286 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Handling Instructions (2659 KB)
References
[1]. 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. [Content Brief]
[2]. Oo ZY, et al. Endogenous Replication Stress Marks Melanomas Sensitive to CHEK1 Inhibitors In Vivo. Clin Cancer Res. 2018 Jun 15;24(12):2901-2912. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
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| H2O / DMSO | 1 mM | 2.2164 mL | 11.0818 mL | 22.1636 mL | 55.4090 mL |
| 5 mM | 0.4433 mL | 2.2164 mL | 4.4327 mL | 11.0818 mL | |
| 10 mM | 0.2216 mL | 1.1082 mL | 2.2164 mL | 5.5409 mL | |
| 15 mM | 0.1478 mL | 0.7388 mL | 1.4776 mL | 3.6939 mL | |
| 20 mM | 0.1108 mL | 0.5541 mL | 1.1082 mL | 2.7705 mL | |
| 25 mM | 0.0887 mL | 0.4433 mL | 0.8865 mL | 2.2164 mL | |
| 30 mM | 0.0739 mL | 0.3694 mL | 0.7388 mL | 1.8470 mL | |
| 40 mM | 0.0554 mL | 0.2770 mL | 0.5541 mL | 1.3852 mL | |
| 50 mM | 0.0443 mL | 0.2216 mL | 0.4433 mL | 1.1082 mL | |
| DMSO | 60 mM | 0.0369 mL | 0.1847 mL | 0.3694 mL | 0.9235 mL |
| 80 mM | 0.0277 mL | 0.1385 mL | 0.2770 mL | 0.6926 mL | |
| 100 mM | 0.0222 mL | 0.1108 mL | 0.2216 mL | 0.5541 mL |
* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.
GDC-0575 dihydrochloride Related Classifications
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