AZD5438

Catalog No.S2621 Batch:S262105

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Technical Data

Formula

C18H21N5O2S
Molecular Weight 371.46 CAS No. 602306-29-6
Solubility (25°C)* In vitro Ethanol 71 mg/mL (191.13 mM)
DMSO 52 mg/mL (139.98 mM)
Water Insoluble
In vivo (Add solvents to the product individually and in order)
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O
8.0mg/ml Taking the 1 mL working solution as an example, add 50 μL of 160 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
Clear solution
5% DMSO 95% Corn oil
1.0mg/ml Taking the 1 mL working solution as an example, add 50 μL of 20 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or 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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

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.
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]
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]
Features A potent inhibitor of cyclin-dependent kinase (CDK) 1, 2, and 9.

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 Assay:

[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.
Animal Study:

[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.

Customer Product Validation

Data from [Data independently produced by Nat Commun, 2014, 5, 3561]

Data from [Data independently produced by Mol Cancer Ther, 2014, 13(3), 662-74]

Data from [Data independently produced by Antimicrob Agents Chemother, 2014, 58(8), 4486-94]

Data independently produced by , , Helen Sadik from Johhns Hopkins University

Selleck's AZD5438 has been cited by 22 publications

Proteogenomics of diffuse gliomas reveal molecular subtypes associated with specific therapeutic targets and immune-evasion mechanisms [ Nat Commun, 2023, 14(1):505] PubMed: 36720864
Nascent transcriptome reveals orchestration of zygotic genome activation in early embryogenesis [ Curr Biol, 2022, 32(19):4314-4324.e7] PubMed: 36007528
Identification of New Vulnerabilities in Conjunctival Melanoma Using Image-Based High Content Drug Screening [ Cancers (Basel), 2022, 14(6)1575] PubMed: 35326726
Phenotypic Screening for Small Molecules that Protect β-Cells from Glucolipotoxicity [ ACS Chem Biol, 2022, 10.1021/acschembio.2c00052] PubMed: 35439415
Whole-exome sequencing of alpha-fetoprotein producing gastric carcinoma reveals genomic profile and therapeutic targets [ Nat Commun, 2021, 12(1):3946] PubMed: 34168152
Integrative discovery of treatments for high-risk neuroblastoma. [ Nat Commun, 2020, 11(1):71] PubMed: 31900415
TGFβ-induced epigenetic deregulation of SOCS3 facilitates STAT3-signaling to promote fibrosis. [ J Clin Invest, 2020, 10.1172/JCI122462] PubMed: 31990678
Cell-cycle-dependent phosphorylation of RRM1 ensures efficient DNA replication and regulates cancer vulnerability to ATR inhibition [ Oncogene, 2020, 10.1038/s41388-020-01403-y] PubMed: 32712628
Single-cell RNA-seq highlights intra-tumoral heterogeneity and malignant progression in pancreatic ductal adenocarcinoma. [ Cell Res, 2019, 29(9):725-738] PubMed: 31273297
Efficient Pre-mRNA Cleavage Prevents Replication-Stress-Associated Genome Instability [ Mol Cell, 2019, 73(4):670-683.e12] PubMed: 30639241

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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