WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 200426
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.
MedKoo Cat#: 200426
Chemical Formula: C18H21N5O2S
Exact Mass: 371.1416
Molecular Weight: 371.45664
Elemental Analysis: C, 58.20; H, 5.70; N, 18.85; O, 8.61; S, 8.63
Synonym: AZD5438; AZD-5438; AZD 5438.
IUPAC/Chemical Name: 4-(1-isopropyl-2-methyl-1H-imidazol-5-yl)-N-(4-(methylsulfonyl)phenyl)pyrimidin-2-amine
InChi Key: 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 Code: O=S(C1=CC=C(NC2=NC=CC(C3=CN=C(C)N3C(C)C)=N2)C=C1)(C)=O
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >5 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
The following data is based on the product molecular weight 371.45664 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
|Concentration / Solvent Volume / Mass||1 mg||5 mg||10 mg|
|1 mM||1.15 mL||5.76 mL||11.51 mL|
|5 mM||0.23 mL||1.15 mL||2.3 mL|
|10 mM||0.12 mL||0.58 mL||1.15 mL|
|50 mM||0.02 mL||0.12 mL||0.23 mL|
1: 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.
2: 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.
3: Camidge DR, Pemberton M, Growcott J, Amakye D, Wilson D, Swaisland H, Forder C, Wilkinson R, Byth K, Hughes A. 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 Chemother Pharmacol. 2007 Sep;60(4):479-88. Epub 2006 Dec 2. PubMed PMID: 17143601.
4: 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.
Phase I study of AZD-5438: Sixty-four patients were included across the three studies (19, 17 and 28, respectively). Nausea and vomiting were the most common adverse events. When dosed continuously, 40 mg four times daily was considered intolerable, and due to safety issues, all studies were terminated prematurely. Consequently, no intolerable dose was identified during the weekly schedule. Pharmacokinetics demonstrated dose-proportional exposure, high interpatient variability and accumulation after multiple doses. Skin biopsies indicated reduced retinoblastoma protein phosphorylation at cdk2 phospho-sites; other pharmacodynamic assessments did not reveal consistent trends. AZD5438 was generally well tolerated in a weekly dosing schedule, but not in continuous schedules. The clinical development programme for AZD5438 was discontinued owing to tolerability and exposure data from these studies (source: Ann Oncol. 2010 Apr;21(4):884-94. ).