| 名稱 | AZD-5438 |
| 描述 | AZD-5438 is an effective inhibitor of CDK, for CDK1(IC50=16 nM), CDK2(IC50=6 nM), CDK9(IC50=20 nM). |
| 細(xì)胞實(shí)驗(yàn) | 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) |
| 激酶實(shí)驗(yàn) | 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. |
| 體外活性 | 在SW620異種移植物模型中,AZD5438對(duì)于各種細(xì)胞周期蛋白（phH3,磷酸核仁素,PP1a等）有以劑量依賴的抑制作用.對(duì)于不同類型的癌癥（乳腺癌,結(jié)腸癌,肺癌,前列腺癌和卵巢癌）,AZD5438通過口服可以對(duì)腫瘤產(chǎn)生抑制作用. |
| 體內(nèi)活性 | AZD5438會(huì)抑制p25-cdk5和糖原合成激酶3β的激酶活性,IC50分別為14 nM和17 nM。 在腫瘤細(xì)胞系中（肺,結(jié)腸直腸,乳腺,前列腺,和血液腫瘤）,AZD5438（IC50=0.2 -1.7 μM）通過抑制cdk-依賴性底物的磷酸化作用誘導(dǎo)細(xì)胞周期阻滯,從而抑制細(xì)胞增殖。在細(xì)胞周期素依賴性激酶中,AZD5438對(duì)于其活性能夠有效抑制,E-cdk2（IC50=6 nM）,A-cdk2（IC50=45 nM）,B1-cdk1（IC50=16 nM）,D3-cdk6（IC50=21 nM）,T-cdk9（IC50=20 nM）。 |
| 存儲(chǔ)條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | H2O : < 1 mg/mL (insoluble or slightly soluble)
Ethanol : 63 mg/mL (169.6 mM)
DMSO : 74 mg/mL (199.21 mM)
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| 關(guān)鍵字 | Cyclin dependent kinase | AZD-5438 | inhibit | AZD 5438 | Inhibitor | CDK |
| 相關(guān)產(chǎn)品 | Sodium Oxamate | Ribociclib | Palbociclib monohydrochloride | Abemaciclib methanesulfonate | CASIN | Olomoucine | Palbociclib | GW 441756 | Dinaciclib | Ro-3306 | GSK 3 Inhibitor IX | Abemaciclib |
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