AZD-7762
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MedKoo CAT#: 200311

CAS#: 860352-01-8 (free base)

Description: AZD-7762 is a synthetic small molecule inhibitor of checkpoint kinases (Chks) with potential chemosensitizing activity. AZD7762 binds 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.

Chemical Structure

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AZD-7762
CAS# 860352-01-8 (free base)
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 200311
Name: AZD-7762
CAS#: 860352-01-8 (free base)
Chemical Formula: C17H19FN4O2S
Exact Mass: 362.12
Molecular Weight: 362.420
Elemental Analysis: C, 56.34; H, 5.28; F, 5.24; N, 15.46; O, 8.83; S, 8.85

Price and Availability

Size Price Availability Quantity
50mg USD 450 2 Weeks
100mg USD 750 2 Weeks
200mg USD 1350 2 Weeks
500mg USD 2850 2 Weeks
1g USD 4250 2 Weeks
2g USD 6950 2 Weeks
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Related CAS #: 860352-01-8 (free base)   1246094-78-9 (HCl)    

Synonym: AZD7762; AZD 7762; AZD-7762.

IUPAC/Chemical Name: (S)-5-(3-fluorophenyl)-N-(piperidin-3-yl)-3-ureidothiophene-2-carboxamide

InChi Key: IAYGCINLNONXHY-LBPRGKRZSA-N

InChi Code: InChI=1S/C17H19FN4O2S/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)/t12-/m0/s1

SMILES Code: O=C(C1=C(NC(N)=O)C=C(C2=CC=CC(F)=C2)S1)N[C@@H]3CNCCC3

Appearance: white solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info: AZD7762, a potent ATP-competitive checkpoint kinase inhibitor in clinical trials. AZD7762 has been profiled extensively in vitro and in vivo in combination with DNA-damaging agents and has been shown to potentiate response in several different settings where inhibition of checkpoint kinase results in the abrogation of DNA damage-induced cell cycle arrest. Dose-dependent potentiation of antitumor activity, when AZD7762 is administered in combination with DNA-damaging agents, has been observed in multiple xenograft models with several DNA-damaging agents, further supporting the potential of checkpoint kinase inhibitors to enhance the efficacy of both conventional chemotherapy and radiotherapy and increase patient response rates in a variety of settings. (source: Mol Cancer Ther. 2008 Sep;7(9):2955-66.). (source: Mol Cancer Ther. 2008 Sep;7(9):2955-66.).    

Product Data:
Product Data
Certificate of Analysis:
View CoA: current batch, Lot#A9O11B18
Safety Data Sheet (SDS):
View Safety Data Sheet (SDS)
Instruction:
View handling instruction
Biological target: AZD-7762 is a potent ATP-competitive checkpoint kinase (Chk) inhibitor in with an IC50 of 5 nM for Chk1.
In vitro activity: As shown in Fig. 1a, MTS assay showed that AZD7762 had no significant inhibitory effect on the proliferation of human osteosarcoma cell lines at low concentrations (≤ 200 nmol/L), and AZD7762 inhibited the two cell lines at higher concentrations (> 200 nmol/L). The effect appeared dose-dependent. The IC50 of AZD7762 on HOS and Saos-2 cell lines were 550 nmol/L and 2.3 μmol/L on 24 h, respectively. For further experiments, this study determined the concentration of AZD7762 to be 100 nmol/L based on the results of MTS and according to the referenced literature. At this concentration, AZD7762 had no significant inhibitory effect on the two osteosarcoma cell lines. Reference: Cancer Cell Int. 2019; 19: 195. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6660702/
In vivo activity: As shown in the orthotopic metastasis model using 4T1 cell line (a mouse breast cancer cell line) carrying luciferase gene, DN10764 treatment significantly suppressed the progression of growth (Figure 6C) as well as lung metastasis (Figure 6D) in a dose-dependent manner. These results were further confirmed in another metastasis model, in which mice were pre-pretreated with DN10764 2 h prior to the injection of MDA-MB-231-luc2-tdTomato cells into the arterial circulation of nude mice via intracardiac injection. As shown in Supplementary Figure S4, compared with vehicle-injected mice, the average bioluminescence at day 43 decreased by 24% or 40% for mice treated with 10 or 20 mg/kg DN1076, respectively. Two dosing regimens (10 mg/kg and 20 mg/kg) did not affect the average animal body weight compared with vehicle groups (Figure 6B and Supplementary Figure S4B). Taken together, these results clearly demonstrated that DN10764 suppressed in vivo tumor progression and metastasis of breast cancer cells. Reference: Oncotarget. 2016 Dec 13; 7(50): 83308–83318. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5347771/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 60.7 167.40
DMF 20.0 55.18
Ethanol 10.0 27.59
PBS (pH 7.2) 10.0 27.59

Preparing Stock Solutions

The following data is based on the product molecular weight 362.42 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Zhu J, Zou H, Yu W, Huang Y, Liu B, Li T, Liang C, Tao H. Checkpoint kinase inhibitor AZD7762 enhance cisplatin-induced apoptosis in osteosarcoma cells. Cancer Cell Int. 2019 Jul 27;19:195. doi: 10.1186/s12935-019-0896-9. PMID: 31372095; PMCID: PMC6660702. 2. Park YH, Kim DK, Kim HW, Kim HS, Lee D, Lee MB, Min KY, Koo J, Kim SJ, Kang C, Kim YM, Kim HS, Choi WS. Repositioning of anti-cancer drug candidate, AZD7762, to an anti-allergic drug suppressing IgE-mediated mast cells and allergic responses via the inhibition of Lyn and Fyn. Biochem Pharmacol. 2018 Aug;154:270-277. doi: 10.1016/j.bcp.2018.05.012. Epub 2018 May 17. PMID: 29777684. 3. Wang L, Wang Y, Chen A, Jalali A, Liu S, Guo Y, Na S, Nakshatri H, Li BY, Yokota H. Effects of a checkpoint kinase inhibitor, AZD7762, on tumor suppression and bone remodeling. Int J Oncol. 2018 Sep;53(3):1001-1012. doi: 10.3892/ijo.2018.4481. Epub 2018 Jul 13. PMID: 30015873; PMCID: PMC6065446. 4. Park JS, Lee C, Kim HK, Kim D, Son JB, Ko E, Cho JH, Kim ND, Nan HY, Kim CY, Yoon S, Lee SH, Choi HG. Suppression of the metastatic spread of breast cancer by DN10764 (AZD7762)-mediated inhibition of AXL signaling. Oncotarget. 2016 Dec 13;7(50):83308-83318. doi: 10.18632/oncotarget.13088. PMID: 27829217; PMCID: PMC5347771.
In vitro protocol: 1. Zhu J, Zou H, Yu W, Huang Y, Liu B, Li T, Liang C, Tao H. Checkpoint kinase inhibitor AZD7762 enhance cisplatin-induced apoptosis in osteosarcoma cells. Cancer Cell Int. 2019 Jul 27;19:195. doi: 10.1186/s12935-019-0896-9. PMID: 31372095; PMCID: PMC6660702. 2. Park YH, Kim DK, Kim HW, Kim HS, Lee D, Lee MB, Min KY, Koo J, Kim SJ, Kang C, Kim YM, Kim HS, Choi WS. Repositioning of anti-cancer drug candidate, AZD7762, to an anti-allergic drug suppressing IgE-mediated mast cells and allergic responses via the inhibition of Lyn and Fyn. Biochem Pharmacol. 2018 Aug;154:270-277. doi: 10.1016/j.bcp.2018.05.012. Epub 2018 May 17. PMID: 29777684.
In vivo protocol: 1. Wang L, Wang Y, Chen A, Jalali A, Liu S, Guo Y, Na S, Nakshatri H, Li BY, Yokota H. Effects of a checkpoint kinase inhibitor, AZD7762, on tumor suppression and bone remodeling. Int J Oncol. 2018 Sep;53(3):1001-1012. doi: 10.3892/ijo.2018.4481. Epub 2018 Jul 13. PMID: 30015873; PMCID: PMC6065446. 2. Park JS, Lee C, Kim HK, Kim D, Son JB, Ko E, Cho JH, Kim ND, Nan HY, Kim CY, Yoon S, Lee SH, Choi HG. Suppression of the metastatic spread of breast cancer by DN10764 (AZD7762)-mediated inhibition of AXL signaling. Oncotarget. 2016 Dec 13;7(50):83308-83318. doi: 10.18632/oncotarget.13088. PMID: 27829217; PMCID: PMC5347771.

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1: Mitchell JB, Choudhuri R, Fabre K, Sowers AL, Citrin D, Zabludoff SD, Cook JA. In vitro and in vivo radiation sensitization of human tumor cells by a novel checkpoint kinase inhibitor, AZD7762. Clin Cancer Res. 2010 Apr 1;16(7):2076-84. Epub 2010 Mar 16. PubMed PMID: 20233881; PubMed Central PMCID: PMC2851146.

2: McNeely S, Conti C, Sheikh T, Patel H, Zabludoff S, Pommier Y, Schwartz G, Tse A. Chk1 inhibition after replicative stress activates a double strand break response mediated by ATM and DNA-dependent protein kinase. Cell Cycle. 2010 Mar;9(5):995-1004. Epub 2010 Mar 14. PubMed PMID: 20160494.

3: Goteti K, Garner CE, Utley L, Dai J, Ashwell S, Moustakas DT, Gönen M, Schwartz GK, Kern SE, Zabludoff S, Brassil PJ. Preclinical pharmacokinetic/pharmacodynamic models to predict synergistic effects of co-administered anti-cancer agents. Cancer Chemother Pharmacol. 2010 Jul;66(2):245-54. Epub 2009 Oct 16. PubMed PMID: 19841922.

4: Wagner JM, Karnitz LM. Cisplatin-induced DNA damage activates replication checkpoint signaling components that differentially affect tumor cell survival. Mol Pharmacol. 2009 Jul;76(1):208-14. Epub 2009 Apr 29. PubMed PMID: 19403702; PubMed Central PMCID: PMC2701464.

5: Zabludoff SD, Deng C, Grondine MR, Sheehy AM, Ashwell S, Caleb BL, Green S, Haye HR, Horn CL, Janetka JW, Liu D, Mouchet E, Ready S, Rosenthal JL, Queva C, Schwartz GK, Taylor KJ, Tse AN, Walker GE, White AM. AZD7762, a novel checkpoint kinase inhibitor, drives checkpoint abrogation and potentiates DNA-targeted therapies. Mol Cancer Ther. 2008 Sep;7(9):2955-66. PubMed PMID: 18790776.

6: Ashwell S, Janetka JW, Zabludoff S. Keeping checkpoint kinases in line: new selective inhibitors in clinical trials. Expert Opin Investig Drugs. 2008 Sep;17(9):1331-40. Review. PubMed PMID: 18694366.