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CDK&Aurora kinase

AZD5438 (602306-29-6)

AZD5438 is a potent inhibitor of CDK1/2/9 with IC50 of 16 nM/6 nM/20 nM. It is less potent to CDK5/6 and also inhibits GSK3β. Phase 1.

Not Intended for Therapeutic Use. For research use only.

CAS: 602306-29-6 Category

AZD5438 (602306-29-6) Description

AZD5438 is a potent inhibitor of cyclin-dependent kinase (cdk) 1, 2, and 9 (IC(50), 16, 6, and 20 nmol/L, respectively). In vitro, AZD5438 showed significant antiproliferative activity in human tumor cell lines (IC(50) range, 0.2-1.7 micromol/L), causing inhibition of the phosphorylation of cdk substrates pRb, nucleolin, protein phosphatase 1a, and RNA polymerase II COOH-terminal domain and blocking cell cycling at G(2)-M, S, and G(1) phases.

AZD5438 potently inhibits the kinase activity of cyclin E-cdk2, cyclin A-cdk2, cyclin B1-cdk1, p25-cdk5, cyclin D3-cdk6, and cyclin T-cdk9 (IC50, 6, 45, 16, 21, and 20 nM, respectively). AZD5438 potently inhibits the kinase activity of cyclin E-cdk2, cyclin A-cdk2, cyclin B1-cdk1, p25-cdk5, cyclin D3-cdk6, and cyclin T-cdk9 (IC50, 6, 45, 16, 21, and 20 nM, respectively). In common with many other cdk inhibitors, AZD5438 also inhibits the kinase activity of p25-cdk5 and glycogen synthase kinase 3β in vitro (IC50, 14 and 17 nM, respectively)[1]. AZD5438 significantly augments cellular radiosensitivity in NSCLC cells. Combined treatment with AZD5438 and irradiation also enhances tumor growth delay, with an enhancement factor ranging from 1.2-1.7.

 

AZD5438 (602306-29-6) Specifications

Product Name AZD5438
Synonyms AZD5438; AZD-5438; AZD 5438.
Chemical Names 4-(1-isopropyl-2-methyl-1H-imidazol-5-yl)-N-(4-(methylsulfonyl)phenyl)pyrimidin-2-amine
Purity ≥98% (HPLC)
CAS Number 602306-29-6
Molecular Formula C18H21N5O2S
Molecular Weight 371.45664
Monoisotopic Mass 371.1416  g/mol
MDL number MFCD11112135
InChIKey WJRRGYBTGDJBFX-UHFFFAOYSA-N
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)
SMILES O=S(C1=CC=C(NC2=NC=CC(C3=CN=C(C)N3C(C)C)=N2)C=C1)(C)=O
Form Powder
Color Off-white solid
Solubility  Soluble in DMSO (>30 mg/ml)
Storage Temp.  −20°C
Shelf life >5 years if stored properly
Handling Protect from air and light
Application A potent inhibitor of CDK1/2/9 with IC50 of 16 nM/6 nM/20 nM

 


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RIDADR NONH for all modes of transport

References:

  • Byth KF, et al. AZD5438, a potent oral inhibitor of cyclin-dependent kinases 1, 2, and 9, leads to pharmacodynamic changes and potent antitumor effects in human tumor xenografts. Mol Cancer Ther. 2009 Jul;8(7):1856-66. Epub 2009 Jun 9.
  • Raghavan P, et al. AZD5438, an Inhibitor of Cdk1, 2, and 9, Enhances the Radiosensitivity of Non-Small Cell Lung Carcinoma Cells. Int J Radiat Oncol Biol Phys. 2012 Jul 12.
  • Boss DS, Schwartz GK, Middleton MR, Amakye DD, Swaisland H, Midgley RS, Ranson M, Danson S, Calvert H, Plummer R, Morris C, Carvajal RD, Chirieac LR, Schellens JH, Shapiro GI. Safety, tolerability, pharmacokinetics and pharmacodynamics of the oral cyclin-dependent kinase inhibitor AZD5438 when administered at intermittent and continuous dosing schedules in patients with advanced solid tumours. Ann Oncol. 2010 Apr;21(4):884-94. Epub 2009 Oct 13. PubMed PMID: 19825886; PubMed Central PMCID: PMC2844945.
  • Byth KF, Thomas A, Hughes G, Forder C, McGregor A, Geh C, Oakes S, Green C, Walker M, Newcombe N, Green S, Growcott J, Barker A, Wilkinson RW. AZD5438, a potent oral inhibitor of cyclin-dependent kinases 1, 2, and 9, leads to pharmacodynamic changes and potent antitumor effects in human tumor xenografts. Mol Cancer Ther. 2009 Jul;8(7):1856-66. Epub 2009 Jun 9. PubMed PMID: 19509270.
  • Camidge DR, Smethurst D, Growcott J, Barrass NC, Foster JR, Febbraro S, Swaisland H, Hughes A. A first-in-man phase I tolerability and pharmacokinetic study of the cyclin-dependent kinase-inhibitor AZD5438 in healthy male volunteers. Cancer Chemother Pharmacol. 2007 Aug;60(3):391-8. Epub 2006 Nov 18. PubMed PMID: 17115157.