Flavopiridol hydrochloride

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Background

Flavopiridol hydrochloride is a selective inhibitor of CDK1, CDK2, CDK4 and CDK6 with IC50 value all ~41 nM as well as CDK7 with 300nM [1] [2] [3].CDKs are protein kinase families which involve in the process of regulating transcription, mRNA processing, cell differentiation and cell cycle. It has been shown that CDKs are abnormally expressed in a variety of cells [3].Flavopiridol hydrochloride is a potent CDK inhibitor and is different from UCN-01. When tested with breast carcinoma cell line MCF-7, flavopiridol hydrochloride treatment showed high inhibitory ability to arrest cell cycle at G1 phase through inhibiting CDK2 and CDK4 [1]. Treated seven lymphoma cell lines with flavopiridol hydrochloride at the concentration of 400 nM, it showed that flavopiridol hydrochloride induced cells apoptosis by inhibiting CDK4, CDK6, CDK7 or CDK9 which in turn inhibited Rb phosphorylation, anti-apoptotic preteins (Mcl-1 and XIAP) [4].In mouse model with HL-60 subcutaneous xenograft, administration of flavopiridol hydrochloride (7.5 mg/kg) intravenously induced advanced stage animals complete regression with 91.67% and remained disease-free several months after one course of flavopiridol treatment [5].It has also been reported that flavopiridol hydrochloride inhibited epidermal growth factoe receptor and protein kinase A with IC50 value of 21 and 122 μM, respectively [3].

[1]. Carlson, B.A., et al., Flavopiridol induces G1 arrest with inhibition of cyclin-dependent kinase (CDK) 2 and CDK4 in human breast carcinoma cells. Cancer Res, 1996. 56(13): p. 2973-8.
[2]. Losiewicz, M.D., et al., Potent inhibition of CDC2 kinase activity by the flavonoid L86-8275. Biochem Biophys Res Commun, 1994. 201(2): p. 589-95.
[3]. Senderowicz, A.M., The cell cycle as a target for cancer therapy: basic and clinical findings with the small molecule inhibitors flavopiridol and UCN-01. Oncologist, 2002. 7 Suppl 3: p. 12-9.
[4]. Ema, Y., et al., Investigation of the cytotoxic effect of flavopiridol in canine lymphoma cell lines. Vet Comp Oncol, 2015.
[5]. Arguello, F., et al., Flavopiridol induces apoptosis of normal lymphoid cells, causes immunosuppression, and has potent antitumor activity In vivo against human leukemia and lymphoma xenografts. Blood, 1998. 91(7): p. 2482-90.