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|Synonyms||AZD 5438;AZD5438; 4-(1-isopropyl-2-methyl-1H-imidazol-5-yl)-N-(4-(methylsulfonyl)phenyl)pyrimidin-2-amine|
AZD5438 is a potent inhibitor of CDK1/2/9 with IC50 of 16 nM/6 nM/20 nM.
|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. ......by AbMole BioScience|
|AZD5438 is a potent inhibitor of cyclin-dependent kinase (CDK) 1, 2 and 9 (IC50 values are 16, 6 and 20 nM respectively). ......by AdooQ BioScience, LLC|
|AZD 5438 is an antiproliferative agent and potent inhibitor of cyclin-dependent kinases Cdk1/cyclin B1 (IC50 = 16 nM), Cdk2/cyclin E (IC50 = 6 nM), Cdk2/cyclin A (IC50 = 45 nM), Cdk6/cyclin D3 (IC50 = 21 nM), and Cdk9/cyclin T (IC50 = 20 nM). AZD5438 also inhibits the kinase activity of p25-cdk5 (IC50 = 14 nM) and glycogen synthase kinase 3β (IC50 = 17 nM). ......by Affix Scientific|
|Description ......by Apexbio Technology LLC|
|AZD5438 is a potent inhibitor of cyclin-dependent kinase (cdk) 1, 2, and 9 (IC(50), 16, 6, and 20 nmol/L, respectively). Broad cdk inhibition may provide an effective method to impair the dysregulated cell cycle that drives tumorigenesis and AZD5438 has t ......by BOC Sciences|
|AZD-5438 is a potent inhibitor of cyclin-dependent kinases (CDKs) (IC₅₀ values are 16, 6 and 20 nM for CDK1, 2, and 9, respectively). Displays antiproliferative activity in human tumor cell lines. It is less potent to CDK5/6 and also inhibits GSK3β. ......by BioVision, Inc.,|
|AZD-5438 is a potent inhibitor of CDK1/2/9 with IC50 of 16 nM/6 nM/20 nM in cell-free assays. It also inhibits GSK3β, but is less potent to CDK5/6. ......by MedChemexpress Co., Ltd.|
|AZD5438 is a potent inhibitor of cyclin-dependent kinase (cdk) 1, 2, and 9 (IC(50), 16, 6, and 20 nmol/L, respectively). In vitro, AZD5438 showed significant antiproliferative activity in human tumor cell lines (IC(50) range, 0.2-1.7 micromol/L), 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 G(2)-M, S, and G(1) phases. ......by MedKoo Biosciences, Inc.|
|A potent and oral inhibitor of CDK1/2/9 with IC50 of 16/6/20 nM, respectively; also inhibits the kinase activity of p25-Cdk5 (IC50=14 nM) and GSK-3β (IC50=17 nM) in vitro, displays 75-fold less active against cyclin D-Cdk4; shows significant antiproliferative activity in human tumor cell lines (IC50 range: 0.2-1.7 uM), inhibits the phosphorylation of Cdk substrates pRb, nucleolin, PP1A, and RNA polymerase II COOH-terminal domain and blocks cell cycle; inhibits the human tumor xenograft growth in vivo; also inhibits PASTA kinase in L. monocytogenes (PrkA) and L. monocytogenes growth in a β-lactam-synergism-dependent manner.Solid TumorsPhase 1 Discontinued ......by ProbeChem|
|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. ......by Selleck Chemicals LLC|
|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. ......by Target Molecule Corp.|
|Potent inhibitor of cyclin-dependent kinase (cdk) 1, 2 and 9 (IC50 values are 16, 6 and 20 nM respectively). Exhibits antiproliferative activity in human tumor cell lines. Blocks cell cycling at G2-M, S and G1 phases; reduces the proportion of actively cycling cells in vivo. ......by Tocris Bioscience Inc.|
|Cell lines||MCF-7, HCT-116, A549, and IM-9|
|Conditions||0 to 10 μM; 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.|
|Source||Selleck Chemicals LLC|
|Animal Models||MCF-7, HCT-116, A549, and IM-9 cells are injected s.c. into the Swiss nude mice and nude rats.|
|Formulation||AZD5438 is dissolved in hydroxy-propyl-methyl-cellulose.|
|Administration||Administered via p.o.|
|Source||Selleck Chemicals LLC|
|Appearance:White to off-white solid||EBNumber:EB000029142|
|Up to one week at 4°C or six months at -20°C.||by Affix Scientific|
|Desiccate at RT||by Tocris Bioscience Inc.|
|DMSO ≥71 mg/mL Water <1.2 mg/mL Ethanol ≥71 mg/mL||by MedChemexpress Co., Ltd.|
|(25°C) * In vitro DMSO 74 mg/mL (199.21 mM); Ethanol74 mg/mL (199.21 mM); Water<1 mg/mL (<1 mM)||by Selleck Chemicals LLC|
|Soluble to 100 mM in DMSO||by Tocris Bioscience Inc.|
|Company||Price and Availability||Country/Region|
|AdooQ BioScience, LLC||USA|
|Affix Scientific||100mg/USD995(In stock);250mg/USD1550(In stock)||USA|
|Apexbio Technology LLC||USA|
|Ark Pharm, Inc.||USA|
|Biochempartner Co., Ltd||China|
|Cayman Chemical Company||USA|
|Excenen Pharmatech Co., Ltd.||China|
|MedChemexpress Co., Ltd.||10mg/USD72();50mg/USD216()||USA|
|MedKoo Biosciences, Inc.||USA|
|Selleck Chemicals LLC||10mg/USD150(In stock);10mM/1mLIn DMSO/USD195(In stock);50mg/USD570(In stock);200mg/USD1670(In stock)||USA|
|Shanghai Haoyuan Chemexpress Co., Ltd.||10mg/USD72();50mg/USD216()||China|
|Target Molecule Corp.||10mg/USD114();50mg/USD198()||USA|
|Tocris Bioscience Inc.||USA|
|Cholest-4-en-3-one, oxime, (3E)-||66538-08-7||C27H45NO||399.65|
|Pparδ agonist 2||870884-12-1||C20H18F3N3O3S||437.44|
|LEE011 (succinate hydrate)||1374639-79-8||C27H38N8O6X||570.64|
. Camidge, D. Ross; Pemberton, Mike; Growcott, Jim; 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. Cancer Chemotherapy and Pharmacology (2007), 60(4), 479-488.
. Camidge, D. Ross; Smethurst, Dominic; A first-in-man phase I tolerability and pharmacokinetic study of the cyclin-dependent kinase-inhibitor AZD5438 in healthy male volunteers. Cancer Chemotherapy and Pharmacology (2007), 60(3), 391-398.
. Raghavan P, Tumati V, Yu L, Chan N, Tomimatsu N, Burma S, Bristow RG, Saha D.AZD5438, an Inhibitor of Cdk1, 2, and 9, Enhances the Radiosensitivity of Non-Small Cell Lung Carcinoma Cells.Int J Radiat Oncol Biol Phys. 2012 Jul 12.
. Boss DS, Schwartz GK, Middleton MR, Amakye DD, Swaisland H, Midgley RS, Ranson M, Danson S, Calvert H, Plummer R, Morris C, Carvajal RD, Chirieac LR, Schellens JH, Shapiro GI.Safety, tolerability, pharmacokinetics and pharmacodynamics of the oral cyclin-dependent kinase inhibitor AZD5438 when administered at intermittent and continuous dosing schedules in patients with advanced solid tumours.Ann Oncol. 2010 Apr;21(4):884-94. Epub 2009 Oct 13.
. Byth KF, Thomas A, Hughes G, Forder C, McGregor A, Geh C, Oakes S, Green C, Walker M, Newcombe N, Green S, Growcott J, Barker A, Wilkinson RW.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.Mol Cancer Ther. 2009 Jul;8(7):1856-66. Epub 2009 Jun 9.
|Byth et al (2009) 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. Mol.Cancer Ther. 8 1856. PMID: 19509270. ......by Tocris Bioscience Inc.|