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5mg |
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25mg |
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50mg |
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Purity: ≥98%
AZD5438 (AZD-5438; AZD 5438) is a novel, potent and selective small molecule inhibitor of cyclin-dependent kinase (CDK) 1, 2 and 9 with potential antineoplastic activity. The inhibitory concentrations of 16 nmol/L, 6 nmol/L, and 20 nmol/L, respectively, are found to inhibit CDK1/2/9. In multiple human tumor cell lines, AZD5438 exhibited noteworthy anti-proliferative activity, with an IC50 ranging from 0.2 μmol/L to 1.7 μmol/L. This resulted in the inhibition of cell cycling at the G2-M, S, and G1 phases as well as the phosphorylation of select proteins, such as CDK substrates pRb, nucleolin, protein phosphatase 1a, and RNA polymerase II COOH-terminal domain.
Targets |
cdk2-cyclin E (IC50 = 6 nM); cdk2-cyclin A (IC50 = 45 nM); cdk5-p25 (IC50 = 14 nM); cdk1-cyclin B1 (IC50 = 16 nM); cdk9-cyclin T (IC50 = 20 nM); cdk6-cyclin D3 (IC50 = 21 nM); cdk4-cyclin D1 (IC50 = 449 nM); cdk7-cyclin H (IC50 = 821 nM)
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ln Vitro |
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ln Vivo |
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Enzyme Assay |
A scintillation proximity assay is used to test AZD5438's capacity to inhibit CDK activity. It involves using recombinant CDK-cyclin complexes of cyclin-Ecdk2, cdk2-cyclin A, cdk4-cyclin D, and recombinant retinoblastoma substrate (amino acids 792-928) or cdk1-cyclin B1 with a peptide substrate derived from the in vitro p34cdc2 phosphorylation site of histone H1 (biotin-X-Pro-Lys-Thr-Pro-Lys-Lys-Ala-Lys-Lys-Leu). Using peptide substrate (AKKPKTPKKAKKLOH), AZD5438's activity against recombinant cdk5/p25 is assessed in a scintillation proximity assay-based assay at 2 μM ATP. By using human purified glycogen synthase kinase 3βenzyme and eukaryotic initiation factor 2B substrate (at 1 μM ATP), the scintillation proximity assay is used to determine the inhibition of glycogen synthase kinase 3β activity. AZD5438 is subjected to a kinase selectivity screening service in which it is screened against cdk6-cyclin D3, cdk7-cyclin H/MAT1 (cdk activating kinase complex), and cdk9-cyclin T.
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Cell Assay |
Solid tumor cell lines are used to test AZD5438. In summary, AZD5438 is added to cells at different concentrations and incubated for 48 hours. After the incubation period, 5-bromo-2′-deoxyuridine (BrdUrd) is pulsed into the cells, and the quantity of DNA synthesis is quantified. Specifically, cell death has no bearing on the IC50 for proliferation inhibition. The following protocol is used to seed multiple myeloma cell lines into 96-well plates: RPMI 1640 supplemented with 10% FCS and glutamine, followed by a 72-hour dose of AZD5438. AlamarBlue is used to measure cell growth, and GI50 values are computed using the pretreatment control values.
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Animal Protocol |
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References |
Molecular Formula |
C18H21N5O2S
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Molecular Weight |
371.46
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Exact Mass |
371.14
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Elemental Analysis |
C, 58.20; H, 5.70; N, 18.85; O, 8.61; S, 8.63
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CAS # |
602306-29-6
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Appearance |
Solid powder
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SMILES |
CC1=NC=C(N1C(C)C)C2=NC(=NC=C2)NC3=CC=C(C=C3)S(=O)(=O)C
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InChi Key |
WJRRGYBTGDJBFX-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C18H21N5O2S/c1-12(2)23-13(3)20-11-17(23)16-9-10-19-18(22-16)21-14-5-7-15(8-6-14)26(4,24)25/h5-12H,1-4H3,(H,19,21,22)
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Chemical Name |
4-(2-methyl-3-propan-2-ylimidazol-4-yl)-N-(4-methylsulfonylphenyl)pyrimidin-2-amine
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Synonyms |
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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 |
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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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Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.6921 mL | 13.4604 mL | 26.9208 mL | |
5 mM | 0.5384 mL | 2.6921 mL | 5.3842 mL | |
10 mM | 0.2692 mL | 1.3460 mL | 2.6921 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.
NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
NCT00088790 | Completed | Drug: AZD5438 | Neoplasms | AstraZeneca | July 2004 | Phase 1 |
Specificity of AZD5438 in human NSCLC cells.Int J Radiat Oncol Biol Phys.2012 Nov 15;84(4):e507-14. th> |
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AZD5438 increased the sensitivity of NSCLC cells to IR.Int J Radiat Oncol Biol Phys.2012 Nov 15;84(4):e507-14. td> |
IR sensitization by AZD5438 was associated with delayed DSB repair in NSCLC cells.Int J Radiat Oncol Biol Phys.2012 Nov 15;84(4):e507-14. td> |
td> |
AZD5438 exhibited G2-M checkpoint arrest in NSCLC cells. td> |