受注:045-509-1970 |
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Synonyms | N/A | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C18H21N5O2S |
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分子量 | 371.46 | CAS No. | 602306-29-6 | |
Solubility (25°C)* | 体外 | DMSO | 74 mg/mL (199.21 mM) | |
Ethanol | 74 mg/mL (199.21 mM) | |||
Water | Insoluble | |||
* <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. |
製品説明 | 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. |
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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] |
特徴 | A potent inhibitor of cyclin-dependent kinase (CDK) 1, 2, and 9. |
キナーゼアッセイ | Recombinant Kinase Assays [1] | |
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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. | ||
細胞アッセイ | 細胞株 | MCF-7, HCT-116, A549, and IM-9 |
濃度 | 0 to 10 μM | |
反応時間 | 48 hours or 72 hours | |
実験の流れ | 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. |
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動物実験 | 動物モデル | MCF-7, HCT-116, A549, and IM-9 cells are injected s.c. into the Swiss nude mice and nude rats. |
投薬量 | ≤100 mg/kg | |
投与方法 | Administered via p.o. |
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]
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 |
長期の保管のために-20°Cの下で製品を保ってください。
人間や獣医の診断であるか治療的な使用のためにでない。
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