AZD5438

Catalog No.S2621

For research use only.

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

AZD5438 Chemical Structure

CAS No. 602306-29-6

Selleck's AZD5438 has been cited by 18 publications

Purity & Quality Control

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Biological Activity

Description AZD5438 is a potent inhibitor of CDK1/2/9 with IC50 of 16 nM/6 nM/20 nM in cell-free assays. It is less potent to CDK5/6 and also inhibits GSK3β. Phase 1.
Features A potent inhibitor of cyclin-dependent kinase (CDK) 1, 2, and 9.
Targets
CDK2 [1]
(Cell-free assay)
CDK1 [1]
(Cell-free assay)
CDK9 [1]
(Cell-free assay)
6 nM 16 nM 20 nM
In vitro

AZD5438 exhibits the potent inhibitory effect on activity of cyclin-dependent kinases including cyclin E-cdk2, cyclin A-cdk2, cyclin B1-cdk1, cyclin D3-cdk6, and cyclin T-cdk9 with IC50 of 6 nM, 45 nM, 16 nM, 21 nM, and 20 nM, respectively. Besides, AZD5438 also inhibits the kinase activity of p25-cdk5 and glycogen synthase kinase 3β with IC50 of 14 nM and 17 nM, respectively. [1] AZD5438 induces cell cycle arrest by inhibiting phosphorylation of cdk-dependent substrates, and exhibits the broad antiproliferative activity against a range of tumor cell lines including lung, colorectal, breast, prostate, and hematologic tumors with IC50 ranging from 0.2 μM (MCF-7) to 1.7 μM (ARH-77). [1]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
human LoVo cells MV7Qdo9tcW[ncnH0bY9vKGG|c3H5 MXm0PEBp NHHmSZdCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFzvWo8h[2WubIOgZZN{\XO|ZXSgZZMhSnKmVTDpcoNwenCxcnH0bY9vKGGodHXyJFQ5KGi{czygTWM2OD1yLk[zJO69VQ>? Ml3iNVg5OTVyM{G=
human LoVo cells M4HCcHBzd2yrZnXyZZRqd25iYYPzZZk> NH;LVGE1QCCq MnG3RY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCOb2\vJINmdGy|IHHzd4V{e2WmIHHzJIlvcGmkaYTpc44hd2ZiQoLkWUBqdmOxcoDvdoF1cW:wIHHmeIVzKDR6IHjyd{whUUN3ME2wMlgh|ryP MYixPFk6PjByNx?=
Assay
Methods Test Index PMID
Western blot p-Chk2 / Chk2 / p-Chk1 / Chk1 22795803
Growth inhibition assay Cell viability 22795803
In vivo In vivo, oral treatment of AZD5438 leads to statistically significant inhibition against the growth of human tumor xenografts derived from a wide range of different cancer types including breast, colon, lung, prostate, and ovarian with maximum TGI ranging from 38% to 153%. [1] In the SW620 xenograft model, AZD5438 causes the inhibition of several cell cycle proteins such as, phH3, phosphonucleolin, PP1a, and several phospho-pRb epitopes in a dose-dependent manner. [1]

Protocol (from reference)

Kinase Assay:[1]
  • Recombinant Kinase Assays [1]:

    The ability of AZD5438 to inhibit cdk activity is examined using a scintillation proximity assay with 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). The activity of AZD5438 against recombinant cdk5/p25 (at 2 μM ATP) is determined in a scintillation proximity assay-based assay using peptide substrate (AKKPKTPKKAKKLOH). Inhibition of glycogen synthase kinase 3β activity is determined with scintillation proximity assay based on the use of human purified glycogen synthase kinase 3βenzyme and eukaryotic initiation factor 2B substrate (at 1 μM ATP). AZD5438 is screened against active recombinant human cdk6-cyclin D3, cdk7-cyclin H/MAT1 (cdk activating kinase complex), and cdk9-cyclin T using the kinase selectivity screening service.

Cell Research:[1]
  • Cell lines: MCF-7, HCT-116, A549, and IM-9
  • Concentrations: 0 to 10 μM
  • Incubation Time: 48 hours or 72 hours
  • Method: AZD5438 is tested against solid tumor cell lines. Briefly, cells are incubated for 48 hours with AZD5438 at a range of concentrations. At the end of incubation, the cells are pulsed with 5-bromo-2′-deoxyuridine (BrdUrd) and the amount of DNA synthesis is measured. The IC50 for inhibition of proliferation is specifically determined independently of cell death. Multiple myeloma cell lines are seeded into 96-well plates in RPMI 1640 supplemented with 10% FCS and glutamine and dosed with AZD5438 for 72 hours. Cell growth is measured using AlamarBlue and GI50 values are calculated with reference to pretreatment control values.
  • (Only for Reference)
Animal Research:[1]
  • Animal Models: MCF-7, HCT-116, A549, and IM-9 cells are injected s.c. into the Swiss nude mice and nude rats.
  • Dosages: ≤100 mg/kg
  • Administration: Administered via p.o.
  • (Only for Reference)

Solubility (25°C)

In vitro

DMSO 74 mg/mL
(199.21 mM)
Ethanol 74 mg/mL
(199.21 mM)
Water Insoluble

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 371.46
Formula

C18H21N5O2S

CAS No. 602306-29-6
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CC1=NC=C(N1C(C)C)C2=NC(=NC=C2)NC3=CC=C(C=C3)S(=O)(=O)C

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Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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