| Size | Price | |
|---|---|---|
| 5mg | ||
| 50mg | ||
| 500mg |
Purity: ≥98%
Ceralasertib formate (AZD6738) is a novel, potent and orally bioavailable morpholino-pyrimidine-based, and selective inhibitor of the ATR (ataxia telangiectasia and rad3 related) kinase with IC50 of 2.5 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 anticancer activity against non-small cell lung cancer (NSCLC). 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. AZD6738 also sensitizes tumor cells to chemo-(e,g, cisplatin) and radiotherapy.
| Targets |
ATR ( IC50 = 1 nM ); PI3Kδ ( IC50 = 6.8 μM ); DYRK ( IC50 = 10.8 μM )
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| ln Vitro |
Ceralasertib (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 the phosphorylation of CHK1 in cells that is dependent on ATR kinase. In non-small cell lung cancer (NSCLC) cell lines, celeralasertib (AZD6738) causes senescence and cell death. Four Kras mutant cell lines are less viable when ceralasertib (AZD6738) is used; H23, H460, A549, and H358 have the lowest GI50 and the largest maximal inhibition (1.05 μM, 88.0% and 2.38 μM, 86.2%, respectively). In NSCLC cell lines with intact ATM kinase signaling, ceralasertib (AZD6738) amplifies the cytotoxicity of CDDP and NSC 613327, and in ATM-deficient NSCLC cells, it potently synergizes with CDDP[1]. With IC50 values less than 1 μM, ceralasertib (AZD6738) inhibits human breast cancer cell lines using the MTT assay. Ceralasertib (AZD6738) causes apoptosis and cell cycle arrest. It suppresses cell proliferative signaling molecules and DNA damage response molecules[2].
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| ln Vivo |
Ceralasertib (AZD6738) and ATR kinase inhibition given daily for 14 days in a row improves CDDP's therapeutic efficacy in xenograft models and is well tolerated by mice. It's amazing how well CDDP and Ceralasertib (AZD6738) work together to treat ATM-deficient lung cancer xenografts[1].
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| Enzyme 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 the phosphorylation of CHK1 in cells that is dependent on ATR kinase.
ATR and ATM are DNA damage signaling kinases that phosphorylate several thousand substrates. ATR kinase activity is increased at damaged replication forks and resected DNA double-strand breaks (DSBs). ATM kinase activity is increased at DSBs. ATM has been widely studied since ataxia telangiectasia individuals who express no ATM protein are the most radiosensitive patients identified. Since ATM is not an essential protein, it is widely believed that ATM kinase inhibitors will be well-tolerated in the clinic. ATR has been widely studied, but advances have been complicated by the finding that ATR is an essential protein and it is widely believed that ATR kinase inhibitors will be toxic in the clinic.
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| Cell Assay |
Ceralasertib (AZD6738) is diluted in DMSO to the appropriate working concentrations after being dissolved at a 30 mM concentration. For Ceralasertib (AZD6738) dose response experiments, the final DMSO concentration in media for all conditions and controls is 0.1%; for Ceralasertib (AZD6738) + chemotherapy viability experiments, it is 0.05%; and for all experiments involving 0.3 μM and 1.0 μM doses of Ceralasertib (AZD6738), it is 0.025%[1].
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| Animal Protocol |
Mice: Ceralasertib (AZD6738) is diluted 1:5 in propylene glycol after being dissolved in DMSO at a concentration of 25 mg/mL or 50 mg/mL. Ceralasertib (AZD6738) is given orally as a gavage for 14 days at a dose of 25 mg/kg (H23) or 50 mg/kg (H460). 10 mL/kg is the dosage volume.[1].
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| References |
[1]. The orally active and bioavailable ATR kinase inhibitor AZD6738 potentiates the anti-tumor effects of CDDP to resolve ATM-deficient non-small cell lung cancer in vivo.Oncotarget. 2015 Dec 29;6(42):44289-305.
[2]. Anti-tumor activity of the ATR inhibitor AZD6738 in HER2 positive breast cancer cells. Int J Cancer. 2017 Jan 1;140(1):109-119. [3]. Lancet.2015 Feb 26;385 Suppl 1:S58. [4]. Sci Rep.2015 Aug 27;5:13545. |
| Molecular Formula |
C21H26N6O4S
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|---|---|
| Exact Mass |
458.1736245
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| Elemental Analysis |
C, 55.01; H, 5.72; N, 18.33; O, 13.96; S, 6.99
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| CAS # |
1352280-98-8
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| Related CAS # |
1352226-88-0;1352280-98-8 (formate);1352226-97-1 (racemic);
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| PubChem CID |
154701782
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| Appearance |
Typically exists as solids (or liquids in special cases) at room temperature
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| tPSA |
154Ų
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| SMILES |
C[C@H]1N(C2=CC(C3([S@@](=N)(C)=O)CC3)=NC(C4=C5C(NC=C5)=NC=C4)=N2)CCOC1.O=CO
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| InChi Key |
JOKLXYXIZOXQHY-FQAMYIAXSA-N
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| InChi Code |
InChI=1S/C20H24N6O2S.CH2O2/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)3-7-22-182-1-3/h3-4,7-8,11,13,21H,5-6,9-10,12H2,1-2H3,(H,22,23)1H,(H,2,3)/t13-,29-/m1./s1
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| Chemical Name |
4-[4-[1-[[S(R)]-S-Methylsulfonimidoyl]cyclopropyl]-6-[(3R)-3-methyl-4-morpholinyl]-2-pyrimidinyl]-1H-pyrrolo[2,3-b]pyridine,
formic acid
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| Synonyms |
AZD-6738; AZD6738; 1352280-98-8; Ceralasertib formate; AKOS040748106; AZD 6738
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| HS Tariff Code |
2934.99.9001
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| 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.) |
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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