| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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Purity: ≥98%
GDC-0575 (also called ARRY-575, RG7741) is a novel, potent and selective inhibitor of CHK1 (Check point kinases) which specifically binds to and inhibits CHK1 with an IC50 of 1.2 nM. This enables tumor cells to escape the cell cycle arrest in the S and G2/M phases that is dependent on CHK1, allowing the cells to undergo DNA repair before going through mitosis. In response to DNA damage, the ATP-dependent serine-threonine kinase CHK1 phosphorylates the cdc25 phosphatases. As a result, CHK1 inhibition may make tumor cells more vulnerable to the damaging effects of some chemotherapy drugs on DNA.
| Targets |
Chk1 (IC50 = 1.2 nM)
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| ln Vitro |
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| ln Vivo |
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| Enzyme Assay |
GDC-0575, also known as ARRY-575 or RG7741, is a novel, strong, and selective inhibitor of CHK1 that binds to it specifically and inhibits it with an IC50 of 1.2 nM.
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| Cell Assay |
In co-culture studies, feeder cells are plated onto type-I collagen-coated 96-well or 6-well plates two days prior to the start of the co-culture and allowed to reach confluence. The culture media is exchanged and they receive a 6.8 Gy radiation one day prior to the start of co-culture. First, AmL cells are plated using the appropriate AmL medium at a density of 2 × 105 cells/mL on day 0 of the co-culture. In incubators with 5% CO2 and indicated oxygen concentrations, cells are cultured at 37°C. Cells are maintained in hypoxia (5% O2) for one week while being treated with 500 nM AraC and/or 100 nM GDC-0575 during short-term culture (STC)[1].
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| Animal Protocol |
Intravenous injections of 1 × 105-106 AmL and 1-3 × 105 hCB CD34+/hBM CD34+ cells are administered to NSG mice. Mice are given a proper 7-day treatment regimen after proving AmL engraftment through FACS analysis of tibia bone marrow aspiration at 9–11 weeks. This includes daily subcutaneous injection of 10 mg/kg AraC, oral gavage of 7.5 mg/kg GDC-0575 suspension every other day, and/or intraperitoneal injection of 300 μg/kg G-CSF every day for 5 days. Mice die from cervical dislocation one week after the last dose. After being dissected, the tibias, pelvis, and femurs are flushed with PBS. Ammonium chloride lyses red blood cells. Human-specific PE-conjugated anti-CD33, PE-FITC-conjugated anti-CD19, PE-Cy7-conjugated anti-CD45, and PERCP-conjugated anti-murine CD45 antibodies are used to stain cells. DAPI staining is used to weed out dead cells and debris. Analysis is done using a BD LSR II flow cytometer. FlowJo software is used for flow cytometry analysis. Over 100,000 DAPI-negative occurrences are gathered. If there is only one population of mCD45-hCD45+CD33+CD19- cells and no mCD45-hCD45+CD33-CD19+ cells nearby, it is considered that AmL is engrained[1].
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| References |
| Molecular Formula |
C16H22BRCL2N5O
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|---|---|
| Molecular Weight |
451.19
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| Exact Mass |
449.03848
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| CAS # |
1657014-42-0
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| Related CAS # |
GDC-0575;1196541-47-5;GDC0575 hydrochloride;1196504-54-7
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| Appearance |
Solid
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| SMILES |
C1C[C@H](CN(C1)C2=C3C(=CNC3=NC=C2Br)NC(=O)C4CC4)N.Cl.Cl
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| InChi Key |
OYMHZTORKRPOBI-YQFADDPSSA-N
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| InChi Code |
InChI=1S/C16H20BrN5O.2ClH/c17-11-6-19-15-13(14(11)22-5-1-2-10(18)8-22)12(7-20-15)21-16(23)9-3-4-9;;/h6-7,9-10H,1-5,8,18H2,(H,19,20)(H,21,23);2*1H/t10-;;/m1../s1
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| Chemical Name |
N-[4-[(3R)-3-aminopiperidin-1-yl]-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl]cyclopropanecarboxamide;dihydrochloride
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| Synonyms |
ARRY-575 2HCl; ARRY-575; ARRY575; RG7741; RG-7741 2HCl; RG 7741; GDC-0575; GDC 0575 2HCl; GDC0575; AK 687476 2HCl; AK-687476; AK687476 dihydrochloric acid
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.17 mg/mL (4.81 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 21.7 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.17 mg/mL (4.81 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 21.7 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.17 mg/mL (4.81 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 10 mg/mL (22.16 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2164 mL | 11.0818 mL | 22.1636 mL | |
| 5 mM | 0.4433 mL | 2.2164 mL | 4.4327 mL | |
| 10 mM | 0.2216 mL | 1.1082 mL | 2.2164 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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