AZD4573

• CAT Number: I020256
• CAS Number: 2057509-72-3
• Molecular Formula: C22H28ClN5O2
• Molecular Weight: 429.94
• Purity: ≥95%
• Synonyms: (1S,3R)-3-acetamido-N-[5-chloro-4-(5,5-dimethyl-4,6-dihydropyrrolo[1,2-b]pyrazol-3-yl)pyridin-2-yl]cyclohexane-1-carboxamide
• InChI: InChI=1S/C22H28ClN5O2/c1-13(29)26-15-6-4-5-14(7-15)21(30)27-20-8-16(18(23)11-24-20)17-10-25-28-12-22(2,3)9-19(17)28/h8,10-11,14-15H,4-7,9,12H2,1-3H3,(H,26,29)(H,24,27,30)/t14-,15+/m0/s1
• InChIKey: AVIWDYSJSPOOAR-LSDHHAIUSA-N
• SMILES: CC(=O)NC1CCCC(C1)C(=O)NC2=NC=C(C(=C2)C3=C4CC(CN4N=C3)(C)C)Cl

AZD4573 is a potent and highly selective CDK9 inhibitor (IC50 of <4 nM) that enables transient target engagement for the treatment of hematologic malignancies[1].
Short-term treatment with AZD4573 led to a rapid dose- and time-dependent decrease in cellular pSer2-RNAPII, resulting in activation of caspase 3 and cell apoptosis in a broad range of haematological cancer cell lines (e.g. caspase activation EC50 13.7 nM in an acute myeloid leukemia model MV4-11) [1].
AZD4573 exhibits a short half-life in multiple species (less than one hour in rat, dog and monkey) and good solubility for intravenous administration[1].

Reference

[1]. Bernard Barlaam, et al. Abstract 1650: Discovery of AZD4573, a potent and selective inhibitor of CDK9 that enables transient target engagement for the treatment of hematologic malignancies. Cancer Research. July 2018. 78(13): Supplement.