Olomoucine

Olomoucine is an ATP competitive inhibitor of CDKs. Olomoucine is a purine (HY-34431) derivative and inhibits CDC2/cyclin B, Cdk2/cyclin A, Cdk2/cyclin E (both IC₅₀=7 µM), CDK/p35 kinase (IC₅₀=3 µM) and ERK1/p44 MAP kinase (IC₅₀=25 µM)^[1][2]. Olomoucine regulates cell cycle and shows anti-melanin tumor activity^[3][4]. IC50 & Target: Target: CDK (cyclin-dependent kinases)^[1] In Vitro: Olomoucine inhibits CDK2 and CDC2 kinases with IC₅₀ of 7 μM (CDC2/cyclin B), 7 μM (CDK2/cyclin A), 7 μM (CDK2/cyclin E), 3 Μm (CDK5/p35), and 25μM (ERK1/p44 MAPK), respectively^[1].
Olomoucine (0, 5, 10, 15, and 25 μM) is a competitive inhibitor for ATP and as a non-competitive inhibitor for histone H^[1].
Olomoucine (0-1000 μM) inhibits DNA synthesis in interleukin-2-stimulated T lymphocytes (CTLL-2 cells) and triggers a Gl arrest similar to interleukin-2 deprivation^[2].
Olomoucine (0-100 μM) inhibits Gl/S transition of non-small cell lung cancer cell line MB65 cells^[2].
Olomoucine (0-150 μM) inhibits prophase/metaphase transition of Rdditapes oocytes^[2].
Olomoucine inhibits tumor cells survival with IC₅₀s of 32.35 μM (dog melanoma), 42.15 μM (mouse B16 melanoma), 82.30 μM (human melanoma), respectively^[3]. In Vivo: Olomoucine (8 mg/kg; i.v.; once daily; 7 d) induces apoptosis in tumor cells on the 3rd day after treatment without side effects^[3].
Cassette dosing was found to overestimate the AUC while underestimating the Cmax compared with single dosing administration^[4].

Cassette dosing pharmacokinetics for olomoucine^[4]

Administration	Cmax (nM)	Clobs (l/h)	Vss(obs) (l)	MRTlast (h)	AUCinf(obs) (nM.h)	t1/2 (h)
cassettle	9208 (0.9)	1.10	0.67 (2.8)/td>	0.56	3030	1.03 (0.7)
single	7194 (0.6)	1.18	0.52 (2.1)/td>	0.40	2831	0.98 (0.7)

Note: Single agents dosing=50 mg/kg, cassette dosing=16.66 mg/kg.