UCN-01

UCN-01 is a synthetic derivative of staurosporine with antiproliferative activity against several in vitro and in vivo cancer models. It inhibits a variety of kinases, including Akt, protein kinase C (IC₅₀ = 30 nM), PDK1 (IC₅₀ = 6 nM) and cyclin-dependent kinases (IC₅₀s = 300-600 nM for Cdk1 and Cdk2). UCN-01 arrests tumor cells in the G₁/S phase of the cell cycle and prevents nucleotide excision repair by inhibiting the G₂ checkpoint kinase Chk1 (IC₅₀ = 7 nM), leading to apoptosis.

UCN 01 is a protein kinase C inhibitor which overrides ZEB1-induced chemoresistance in hepatocellular cancer in human. A cell-permeable Staurosporine derived anticancer agent that inhibits several protein kinases.

UCN-01 is an indolocarbazole isolated from a high staurosporine-producing Streptomyces culture. UCN-01 inhibits protein kinase C (PKC) and cyclin-dependant kinase 2 (CDK2), resulting in accumulation of cells in the G1 phase and induction of apoptosis. UCN-01 also enhances the cytotoxicity of other anti-cancer drugs, such as DNA-damaging agents and anti-metabolite drugs, through putative abrogation of G2 and/or S phase accumulation induced by the latter agents.

A cell-permeable Staurosporine (Cat. No. 569397) derived anticancer agent that reversibly and ATP-competitively inhibits several protein kinases (IC₅₀ = 29 nM, 34 nM, 30 nM, 590 nM and 530 nM for PKCα, PKCβ, PKCγ, PKCδ and PKCε; IC₅₀ = 7 nM, 27 nM, 50 nM, 50 nM, 150 nM and 1.04 M for Chk1, Cdc25C-associated protein kinase 1, Cdk1, PAK4, Cdk5/p25 and Chk2; IC₅₀ = 33 nM, 50 nM, 95 nM, 500 nM, 500 nM and 1.0 M for PDK1, lck, MAPKAP kinase-2, Akt, GSK-3β and PKA, respectively). At higher concentrations (>15 M), affects the activities of Src, PIM-1, CKII, DNA-PK, ErK1, ILK-1 and MAPKK1). Reported to suppress thymidylate synthase expression, induce apoptosis with caspase activation, and sensitize tumor cells to a range of DNA-damaging agents.

Cell permeable: yes

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[5] TAKAHIRO YAMAUCHI  William P  Michael J Keating. UCN-01 (7-hydroxystaurosporine) inhibits DNA repair and increases cytotoxicity in normal lymphocytes and chronic lymphocytic leukemia lymphocytes.[J]. Molecular Cancer Therapeutics, 2002, 1 4: 287-294.
[6] MARIA M FACCHINETTI. UCN-01-induced cell cycle arrest requires the transcriptional induction of p21(waf1/cip1) by activation of mitogen-activated protein/extracellular signal-regulated kinase kinase/extracellular signal-regulated kinase pathway.[J]. Cancer research, 2004, 64 10: 3629-3637. DOI: 10.1158/0008-5472.can-03-3741