| Identification | Back Directory | [Name]
AZD 5438 | [CAS]
602306-29-6 | [Synonyms]
AZD
CS-1903
AZD 5438
AZD5438, >=98%
AZD 5438; AZD5438
AZD 5438 USP/EP/BP
AZD5438 >=97% (HPLC)
4-[2-Methyl-1-(1-Methylethyl)-1H-iMidazol-5-yl]-N-[4-(Methylsulfonyl)phenyl]-
4-[2-Methyl-1-isopropyl-1H-imidazol-5-yl]-N-[4-(methylsulfonyl)phenyl]-2-pyrimidinamine
4-[2-Methyl-1-(1-methylethyl)-1H-imidazol-5-yl]-N-[4-(methylsulfonyl)phenyl]-2-pyrimidinamine
2-Pyrimidinamine,4-[2-methyl-1-(1-methylethyl)-1H-imidazol-5-yl]-N-[4-(methylsulfonyl)phenyl]-
AZD 5438
4-[2-Methyl-1-isopropyl-1H-imidazol-5-yl]-N-[4-(methylsulfonyl)phenyl]-2-pyrimidinamine
2-Pyrimidinamine,4-[2-methyl-1-(1-methylethyl)-1H-imidazol-5-yl]-N-[4-(methylsulfonyl)phenyl]-(AZD 5438)
4-[2-Methyl-1-isopropyl-1H-imidazol-5-yl]-N-[4-(methylsulfonyl)phenyl]-2-pyrimidinamine AZD 5438 | [Molecular Formula]
C18H21N5O2S | [MDL Number]
MFCD11112135 | [MOL File]
602306-29-6.mol | [Molecular Weight]
371.46 |
| Chemical Properties | Back Directory | [Boiling point ]
655.2±65.0 °C(Predicted) | [density ]
1.31 | [storage temp. ]
Keep in dark place,Inert atmosphere,2-8°C | [solubility ]
insoluble in H2O; ≥18.55 mg/mL in DMSO; ≥42.1 mg/mL in EtOH | [form ]
solid | [pka]
4.08±0.50(Predicted) | [color ]
White to light yellow | [InChI]
InChI=1S/C18H21N5O2S/c1-12(2)23-13(3)20-11-17(23)16-9-10-19-18(22-16)21-14-5-7-15(8-6-14)26(4,24)25/h5-12H,1-4H3,(H,19,21,22) | [InChIKey]
WJRRGYBTGDJBFX-UHFFFAOYSA-N | [SMILES]
C1(NC2=CC=C(S(C)(=O)=O)C=C2)=NC=CC(C2N(C(C)C)C(C)=NC=2)=N1 |
| Hazard Information | Back Directory | [Uses]
AZD 5438 is a potent oral inhibitor of cyclin-dependent kinases 1, 2, and 9, which leads to leads to pharmacodynamic changes and potent antitumor effects in human tumor xenografts. | [Definition]
ChEBI: 4-(2-methyl-3-propan-2-yl-4-imidazolyl)-N-(4-methylsulfonylphenyl)-2-pyrimidinamine is a sulfonamide. | [Biological Activity]
azd5438 is a potent small molecule inhibitor of cyclin-dependent kinase (cdk) 1, 2 and 9 with half maximal inhibitory concentration ic50 of 16 nmol/l, 6 nmol/l and 20 nmol/l respectively. azd5438 has also been found to potently inhibit the human cyclin e/cdk2 complex, the cyclin b1/cdk1 complex and the cyclin a/cdk2 complex with ic50 of 0.006 μm, 0.016 μm and 0.045 μm respectively. in previous studies, azd5438 has exhibited significant anti-proliferative activity in a few human tumor cell lines with ic50 ranging from 0.2 μmol/l to 1.7 μmol/l, in which the phosphorylation of a few proteins, including cdk substrates prb, nucleolin, protein phosphatase 1a and rna polymerase ii cooh-terminal domain, and cell cycling at g2-m, s and g1 phases were inhibited. | [in vivo]
AZD5438 (50 mg/kg twice daily or 75 mg/kg, p.o.) inhibits human tumor xenograft growth. In vivo, AZD5438 reduces the proportion of actively cycling cells. Further pharmacodynamic analysis of AZD5438-treated SW620 xenografts shows that efficacious doses of AZD5438 (>40% tumor growth inhibition) maintains suppression of biomarkers, such as phospho-pRbSer249/Thr252, for up to 16 hours following a single oral dose[1]. | [IC 50]
cdk2-cyclin E: 6 nM (IC50); cdk2-cyclin A: 45 nM (IC50); cdk5-p25: 14 nM (IC50); cdk1-cyclin B1: 16 nM (IC50); cdk9-cyclin T: 20 nM (IC50); cdk6-cyclin D3: 21 nM (IC50); cdk4-cyclin D1: 449 nM (IC50); cdk7-cyclin H: 821 nM (IC50) | [storage]
Desiccate at RT | [References]
[1]camidge dr1, smethurst d, growcott j, barrass nc, foster jr, febbraro s, swaisland h, hughes a. a first-in-man phase i tolerability and pharmacokinetic study of the cyclin-dependent kinase-inhibitor azd5438 in healthy male volunteers. cancer chemother pharmacol. 2007 aug;60(3):391-8. epub 2006 nov 18.
[2]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. doi: 10.1158/1535-7163.mct-08-0836. epub 2009 jun 9. |
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