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Description: Ceralasertib (formerly AZD6738), a morpholino-pyrimidine-based DNA damage repair agent, is a potent, orally bioavailable and selective inhibitor of ATR (ataxia telangiectasia and rad3 related) kinase with potential antitumor activity. It inhibits ATR with an IC50 of 1 nM. ATR is a serine/threonine protein kinase that is upregulated in various cancer cells. It is currently being investigated in phase I clinical trials for cancer treatment.
References: Lancet. 2015 Feb 26;385 Suppl 1:S58; Sci Rep. 2015 Aug 27;5:13545.
Related CAS: 1352280-98-8 (formic acid); 1352226-97-1 (racemate)
Product Catalog 2022
Guide to Product Handling
AZD6738; AZD-6738;AZD 6738
Chemical Name: (R)-imino(methyl)(1-(6-((R)-3-methylmorpholino)-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)pyrimidin-4-yl)cyclopropyl)-l6-sulfanone
InChi Key: OHUHVTCQTUDPIJ-JYCIKRDWSA-N
InChi Code: InChI=1S/C20H24N6O2S/c1-13-12-28-10-9-26(13)17-11-16(20(5-6-20)29(2,21)27)24-19(25-17)15-4-8-23-18-14(15)3-7-22-18/h3-4,7-8,11,13,21H,5-6,9-10,12H2,1-2H3,(H,22,23)/t13-,29-/m1/s1
SMILES Code: C[[email protected]@](=O)(C1(CC1)C2=NC(C3=C4C=CNC4=NC=C3)=NC(N5CCOC[[email protected]]5C)=C2)=N
Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
This equation is commonly abbreviated as: C1V1 = C2V2
In vitro activity: AZD6738 is an orally available morpholino-pyrimidine-based, and selective inhibitor of the ATR (ataxia telangiectasia and rad3 related) kinase with IC50 of 1 nM. ATR is a serine/threonine protein kinase that is upregulated in various cancer cells, it plays a key role in DNA repair, cell cycle progression, and survival; it is activated by DNA damage caused during DNA replication-associated stress. AZD6738 has potential antineoplastic activity. Upon administration by oral route, AZD6738 selectively inhibits ATR activity by blocking the downstream phosphorylation of the serine/threonine protein kinase CHK1, which prevents ATR-mediated signaling, and results in the inhibition of DNA damage checkpoint activation, disruption of DNA damage repair, and the induction of tumor cell apoptosis. In an in vitro model capable of reproducing, over 70 hours after the initiation of the treatment with AZD6738, the γH2AX signal was sustained. Stalled replication forks may collapse the formation of DNA double stranded breaks and the activation of the ataxia telangiectasia mutated (ATM) kinase. As a single agent across cancer cell line panels, AZD6738 is active. In cell lines lacking ATM-pathway, the sensitivity of AZD6738 was enhanced.
Kinase Assay: AZD6738 is a potent inhibitor of ATR kinase activity with an IC50 of 0.001 μM against the isolated enzyme and 0.074 μM against ATR kinase-dependent CHK1 phosphorylation in cells.
Cell Assay: AZD6738 is dissolved in DMSO at 30 mM and diluted in DMSO to desired working concentrations. The final DMSO concentration in media for all conditions and controls is 0.1% for AZD6738 dose response experiments, 0.05% for AZD6738 + chemotherapy viability experiments, and 0.025% for all experiments involving 0.3 μM and 1.0 μM doses of AZD6738.
Purity ≥98%
COA
MSDS
Inhibition of ATR by AZD6738 inhibits growth of NSCLC cells and induces a DNA damage response. Oncotarget. 2015 Dec 29;6(42):44289-305.
AZD6738 sensitizes NSCLC cell lines to cisplatin and synergizes strongly with cisplatin in ATM-deficient H23 cells. Oncotarget. 2015 Dec 29;6(42):44289-305.
The combination of AZD6738 and cisplatin causes accumulation of cells in early S-phase and at the G1/S border. Oncotarget. 2015 Dec 29;6(42):44289-305.
The combination of AZD6738 and cisplatin causes dramatic cell death of ATM-deficient cells independent of the ATM-p53 signaling pathway. Oncotarget. 2015 Dec 29;6(42):44289-305.
AZD6738 sensitizes ATM knockdown cells to cisplatin. Oncotarget. 2015 Dec 29;6(42):44289-305.
AZD6738 potentiates cisplatin efficacy in NSCLC xenografts, and the combination causes rapid regression of ATM-deficient H23 tumors. Oncotarget. 2015 Dec 29;6(42):44289-305.