AZD5597 [(S)-(4-((5-fluoro-4-(1-isopropyl-2-methyl-1H-imidazol-5-yl)pyrimidin-2-yl)amino)phenyl)(3-(methylamino)pyrrolidin-1-yl)methanone]
is a potent and selective cyclin-dependent kinase (CDK) inhibitor from a novel
series of imidazole pyrimidine amides developed at AstraZeneca. It inhibits
both CDK1 and CDK2 with an IC50 value of 0.002 uM, respectively.
The overall profile of AZD5597 indicated that it was
suitable for further development as an iv
agent. The high margins against hERG allow for flexibility in dosing either as
a bolus or by extended infusions. The lack of CYP inhibition lowers the risk of
problematic drug–drug interactions in the clinic. Excellent aqueous solubility
from crystalline AZD5597 was obtained, even in simple saline formulations. In
addition, the formulated drug showed no significant decomposition on exposure
to light, plasma or through chemical hydrolysis.
Based on high levels of both enzyme potency and cellular
anti-proliferative activity, AZD3147 was selected by AstraZeneca for further
development.
Common Name: AZD5597
Synonyms: AZD-5597; AZD 5597; AZD5597
IUPAC Name: (S)-(4-((5-fluoro-4-(1-isopropyl-2-methyl-1H-imidazol-5-yl)pyrimidin-2-yl)amino)phenyl)(3-(methylamino)pyrrolidin-1-yl)methanone
CAS Number: 924641-59-8
SMILES: FC1=CN=C(NC2=CC=C(C(N3C[C@@H](NC)CC3)=O)C=C2)N=C1C4=CN=C(C)N4C(C)C
Mechanism of Action: Kinase Inhibitor; CDK Inhibitor; CDK2
Inhibitor; CDK1 Inhibitor
Indication: Various Cancers; Anti-tumor Therapy
Development Stage: Investigational
Company: AstraZeneca
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Eidogen Sertanty Inc Provides
Kinase Knowledge Base (KKB): a Collection of nearly 1.6 M Kinase Inhibitors.
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The
mammalian target of rapamycin (mTOR), a serine/theronine kinase of
approximately 289 kDa in size, is a member of the evolutionary conserved
eukaryotic PI3K-related kinase (PIKK) family of atypical protein kinases which
also include the protein kinases DNA-PK (DNA dependent protein kinase), ATM
(ataxia-telangiectasia mutated) and ATR (ataxiatelangiectasia and Rad3
related). mTOR is a key target in the development of antitumor therapies. Activated
by growth factor/mitogenic stimulation activation of the phosphatidylinositol
3-kinase (PI3K)/Akt signaling pathway, mTOR is a central regulator of cell
growth and proliferation. This PI3K-Akt-mTOR pathway is one of the most
frequently dysregulated pathways in cancer [1].
References:
1. Jones, C. D.; et.
al. The discovery of AZD5597, a potent imidazole pyrimidine amide CDK
inhibitor suitable for intravenous dosing. Bioorg Med Chem Lett 2008, 18(24), 6369-6373.
