AZD-5438

• CAT Number: I004265
• CAS Number: 602306-29-6
• Molecular Formula: C18H21N5O2S
• Molecular Weight: 371.50
• Purity: ≥95%
• Synonyms: 4-(2-methyl-3-propan-2-ylimidazol-4-yl)-N-(4-methylsulfonylphenyl)pyrimidin-2-amine
• Target: Cyclin-Dependent Kinases
• Solubility: DMSO ≥71 mg/mL Water <1.2 mg/mL Ethanol ≥71 mg/mL
• Storage: 2-8°C
• IC50: 16 nM(CDK1); 6 nM(CDK2); 20 nM(CDK9)
• InChI: 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)
• InChIKey: WJRRGYBTGDJBFX-UHFFFAOYSA-N
• SMILES: CC1=NC=C(N1C(C)C)C2=NC(=NC=C2)NC3=CC=C(C=C3)S(=O)(=O)C

AZD5438（Cat No.:I004265）is a highly potent inhibitor that targets cyclin-dependent kinases (CDK) 1, 2, and 9, with IC50 values of 16 nM, 6 nM, and 20 nM, respectively, in cell-free assays. It exhibits a slightly weaker effect on CDK5 and CDK6. Additionally, AZD5438 demonstrates inhibitory activity against glycogen synthase kinase 3 beta (GSK3β). By targeting these kinases, AZD5438 has the potential to regulate cell cycle progression and inhibit cell proliferation, making it a promising candidate for anticancer therapeutics and the treatment of other diseases involving dysregulated CDK activity.

Reference

[1]. Camidge, D. Ross; Pemberton, Mike; Growcott, Jim; A phase I pharmacodynamic study of the effects of the cyclin-dependent kinase-inhibitor AZD5438 on cell cycle markers within the buccal mucosa, plucked scalp hairs and peripheral blood mononucleocytes of healthy male volunteers. Cancer Chemotherapy and Pharmacology (2007), 60(4), 479-488.
[2]. Camidge, D. Ross; Smethurst, Dominic; A first-in-man phase I tolerability and pharmacokinetic study of the cyclin-dependent kinase-inhibitor AZD5438 in healthy male volunteers. Cancer Chemotherapy and Pharmacology (2007), 60(3), 391-398.
[3]. Raghavan P, Tumati V, Yu L, Chan N, Tomimatsu N, Burma S, Bristow RG, Saha D.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.
[4]. 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.
[5]. 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.