AZD5438 | AZD 5438 | CAS#602306-29-6 | CDK inhibitor

MedKoo Cat#: 200426 | Name: AZD5438

Description:

WARNING: This product is for research use only, not for human or veterinary use.

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.

Chemical Structure

AZD5438

CAS#602306-29-6

Theoretical Analysis

MedKoo Cat#: 200426

Name: AZD5438

CAS#: 602306-29-6

Chemical Formula: C18H21N5O2S

Exact Mass: 371.1416

Molecular Weight: 371.46

Elemental Analysis: C, 58.20; H, 5.70; N, 18.85; O, 8.61; S, 8.63

Price and Availability

Size	Price	Availability	Quantity
10mg	USD 350.00	2 Weeks
50mg	USD 950.00	2 Weeks

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Related CAS #

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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

More Info

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. ).

Product Data

Product Data

Instruction

View handling instruction

Biological target:

AZD-5438 is a potent CDK1, CDK2, and CDK9 inhibitor, with IC50s of 16 nM, 6 nM, and 20 nM in cell-free assays, respectively.

In vitro activity:

The most conspicuous changes observed in AZD5438-treated cells included cell shrinkage, increased brightness, and detachment from the substratum. These changes became visible after 72h of AZD5438 treatment but were absent in control cells treated with DMSO, suggesting that cells treated with AZD5438 died by apoptosis. Reference: Apoptosis. 2014 Mar; 19(3): 451–466. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3945523/

In vivo activity:

In addition, mouse pretreatment experiments using a single dose of AZD5438 (75 mg/kg) delivered via oral gavage demonstrated that AZD5438 protected against both cisplatin- and noise-induced hearing loss (fig. S7, A to D). Reference: Sci Adv. 2020 Dec; 6(49): eabd0561. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821884/

	Solvent	mg/mL	mM
Solubility
	DMSO	57.8	155.58
	DMF	20.0	53.84
	Ethanol	37.1	99.88

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 371.46 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

Formulation protocol:

1. Bhattacharya S, Ray RM, Johnson LR. Cyclin-dependent kinases regulate apoptosis of intestinal epithelial cells. Apoptosis. 2014 Mar;19(3):451-66. doi: 10.1007/s10495-013-0942-3. PMID: 24242917; PMCID: PMC3945523. 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. doi: 10.1158/1535-7163.MCT-08-0836. Epub 2009 Jun 9. PMID: 19509270. 3. Ingersoll MA, Malloy EA, Caster LE, Holland EM, Xu Z, Zallocchi M, Currier D, Liu H, He DZZ, Min J, Chen T, Zuo J, Teitz T. BRAF inhibition protects against hearing loss in mice. Sci Adv. 2020 Dec 2;6(49):eabd0561. doi: 10.1126/sciadv.abd0561. PMID: 33268358; PMCID: PMC7821884.

In vitro protocol:

In vivo protocol:

1. Ingersoll MA, Malloy EA, Caster LE, Holland EM, Xu Z, Zallocchi M, Currier D, Liu H, He DZZ, Min J, Chen T, Zuo J, Teitz T. BRAF inhibition protects against hearing loss in mice. Sci Adv. 2020 Dec 2;6(49):eabd0561. doi: 10.1126/sciadv.abd0561. PMID: 33268358; PMCID: PMC7821884. 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. doi: 10.1158/1535-7163.MCT-08-0836. Epub 2009 Jun 9. PMID: 19509270.

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.

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Description:

Chemical Structure

Theoretical Analysis

Price and Availability

Preparing Stock Solutions

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