| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg |
|
||
| Other Sizes |
|
Purity: ≥98%
AZD7762 HCl (AZD-7762) is a novel, potent, selective, ATP-competitive, and synthetic small molecule checkpoint kinase (Chk) inhibitor with anticancer activity. It has an IC50 of 5 nM for Chk1. AZD-7762 has potential chemosensitizing activity by binding to and inhibits Chks, which may prevent cell cycle arrest and subsequent nucleotide excision repair in DNA-damaged tumor cells, resulting in tumor cell apoptosis. This agent may enhance the cytotoxicity of DNA-damaging agents. Chks are protein kinases that regulate either G1/S or G2/M transitions in the cell cycle. In the presence of DNA damage or incomplete DNA replication, Chks become activated and initiate cell cycle arrest to allow DNA repair or the completion of DNA replication.
| ln Vitro |
In vitro, AZD-7762 hydrochloride corrects Chk1 and Chk2 just as well. AZD-7762 hydrochloride increases the effectiveness of NSC 613327 and SKF 104864A, suppresses DNA damage-induced S and G2 checkpoints, and modifies downstream checkpoint diluting proteins. By using the scintillation taxis assay, the AZD-7762 salt was found to potently block Chk1 phosphorylation of the cdc25C peptide, with an IC50 of 5 nM. It was found that the salt AZD-7762 had a Ki of 3.6 nM. According to kinetic characterization, AZD-7762 salt binds to Chk1's ATP binding site where it is assumed to engage in direct, reversible competition for ATP binding. It was demonstrated that AZD-7762 hydrochloride could completely remove camptothecin-induced G2 blockage, with a maximal elimination range of 100 nM and an average EC50 of 10 nM (n=12) [1].
|
|---|---|
| ln Vivo |
AZD-7762 hydrochloride (10 mg/kg and 20 mg/kg) dose-dependently increased the anticancer efficacy of NSC 613327 in H460-DNp53 xenograft experiments. In other words, the inhibition rates (%T /C) drop to 48% and 32%, respectively, as the dose increases. When used in conjunction with CPT-11 in a mouse xenograft research, AZD-7762 hydrochloride dramatically raised CPT-11 activity and %T/C to -66% and -66%, respectively. -67% [1]. When combined with CX-5461, AZD7762 hydrochloride causes both internal and exterior apparent cell death in Tp53-null (Tp53-/-) Eμ-Myc [2].
|
| References |
[1]. Zabludoff SD, et al. AZD7762, a novel checkpoint kinase inhibitor, drives checkpoint abrogation and potentiates DNA-targeted therapies. Mol Cancer Ther. 2008 Sep;7(9):2955-66.
[2]. Quin J, et al. Inhibition of RNA polymerase I transcription initiation by CX-5461 activates non-canonical ATM/ATR signaling. Oncotarget. 2016 Aug 2;7(31):49800-49818. |
| Molecular Formula |
C17H20CLFN4O2S
|
|---|---|
| Molecular Weight |
398.8827
|
| CAS # |
1246094-78-9
|
| Related CAS # |
AZD-7762;860352-01-8
|
| SMILES |
O=C(C1=C(NC(N)=O)C=C(C2=CC=CC(F)=C2)S1)N[C@@H]3CNCCC3.[H]Cl
|
| InChi Key |
WFZBLOIXZRZEDG-YDALLXLXSA-N
|
| InChi Code |
InChI=1S/C17H19FN4O2S.ClH/c18-11-4-1-3-10(7-11)14-8-13(22-17(19)24)15(25-14)16(23)21-12-5-2-6-20-9-12;/h1,3-4,7-8,12,20H,2,5-6,9H2,(H,21,23)(H3,19,22,24);1H/t12-;/m0./s1
|
| Chemical Name |
(S)-5-(3-Fluorophenyl)-N-(piperidin-3-yl)-3-ureidothiophene-2-carboxamide Hydrochloride
|
| Synonyms |
AZD-7762 Hydrochloride; AZD-7762 HCl; AZD7762; AZD 7762; AZD-7762.
|
| 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)
|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
|---|
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5070 mL | 12.5351 mL | 25.0702 mL | |
| 5 mM | 0.5014 mL | 2.5070 mL | 5.0140 mL | |
| 10 mM | 0.2507 mL | 1.2535 mL | 2.5070 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.
Effect of AZD7762 on cell cycle proteins following treatment of cells with DNA-damaging agents.Mol Cancer Ther.2008 Sep;7(9):2955-66. |
|---|
AZD7762 potentiated gemcitabine and topotecan.Mol Cancer Ther.2008 Sep;7(9):2955-66. |
AZD7762 potentiated gemcitabine in rodent xenograft efficacy models.Mol Cancer Ther.2008 Sep;7(9):2955-66. |
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA
