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AZD5438

Cat. No. M1810
AZD5438 Structure
Synonym:

AZD 5438

Size Price Availability Quantity
25mg USD 110 In stock
50mg USD 230 In stock
100mg USD 390 In stock
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Quality Control
Biological Activity

AZD5438 is a novel, orally bioavailable, cyclin-dependent kinase (CDK) inhibitor demonstrating preclinical pharmacodynamic (PD) effects on CDK substrates and active growth inhibition of human tumour xenografts. In vitro, AZD5438 showed significant antiproliferative activity in human tumor cell lines (IC50 range, 0.2-1.7 μM), 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 G2-M, S, and G1 phases. AZD5438 blocks cell cycling at G2-M, S and G1 phases; reduces the proportion of actively cycling cells in vivo. The modest PD effect, short plasma t1/2 and close PK-PD relationship suggest that multiple daily dosing or sustained release formulations at higher doses will be necessary for AZD5438 to achieve sustained inhibition of CDK in human cancers.

Protocol
Cell Experiment
Cell lines MCF-7, MDA-MB-231, HCT-116, HT29, LoVo, SW620, Colo-205 cells line
Preparation method Measurement of Cell Proliferation
AZD5438 was tested against solid tumor cell lines as previously described. Briefly, cells were incubated for 48 h with AZD5438 at a range of concentrations. At the end of incubation, the cells were pulsed with 5-bromo-2′-deoxyuridine (BrdUrd) and the amount of DNA synthesis was measured. The IC50 for inhibition of proliferation was specifically determined independently of cell death. Multiple myeloma cell lines were seeded into 96-well plates in RPMI 1640 supplemented with 10% FCS and glutamine and dosed with AZD5438 for 72 h. Cell growth was measured using AlamarBlue (Invitrogen) and GI50 values were calculated with reference to pretreatment control values.
Concentrations 0~10 μ M
Incubation time 72 h
Animal Experiment
Animal models human HX147 tumor xenografts in Swiss nude (nu/nu genotype; AstraZeneca) mice
Formulation prepared in hydroxy-propyl-methyl-cellulose
Dosages 37.5-75 mg/kg once or twice daily for ~3 wk
Administration oral gavage
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Chemical Information
Molecular Weight 371.46
Formula C18H21N5O2S
CAS Number 602306-29-6
Purity >99%
Solubility DMSO
Ethanol
Storage at -20°C
References

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.
Byth KF, et al. Mol Cancer Ther. 2009 Jul;8(7):1856-66. PMID: 19509270.

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.
Camidge DR, et al. Cancer Chemother Pharmacol. 2007 Sep;60(4):479-88. PMID: 17143601.

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  Catalog
Abmole Inhibitor Catalog 2017




Keywords: AZD5438, AZD 5438 supplier, CDK, inhibitors

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