CDK1-IN-1 is a potent CDK1 inhibitor (CDK1/CycB IC50 =161.2 nM) with potential antiproliferative activity and selectivity for cancer tissues. CDK1-IN-1 induces apoptosis in p53 dependent manner through the intrinsic apoptotic pathway. CDK1-IN-1 is a potential targeted antitumor agent [1].
In Vitro, CDK1-IN-1 (compound 7a) (10 µM, 48 hours) has the high antiproliferative activity with a mean percentage of growth inhibition of 48.5 % over NCI cancer cell lines, and caused more than 40% growth inhibition in 36 cancer cell lines from different cancer subtypes[1]. CDK1-IN-1 (0.1-100 μM, 48 hours) has better selectivity for cancer cells over normal cell lines (IC50 of 17.7 and 6.28 μM in WI-38 and HCT-116 cells, respectively; SI=2.8)[1]. CDK1-IN-1 (17.7 μM in WI-38 and 6.28 μM in HCT-116; 48 hours) has a superior activity on cancerous cells than normal cells in inducing apoptosis and arresting the cell cycle at the G2/M phase[1]. CDK1-IN-1 (17.7 μM in WI-38 and 6.28 μM in HCT-116; 48 hours) can cause cell death mainly through apoptosis rather than necrosis and confirmed that its activity is more selective to cancerous cells than normal cells[1]. CDK1-IN-1 (6.28 μM; 48 hours) induce apoptosis in p53 dependent manner through the intrinsic apoptotic pathway in HCT-116 cells[1].
References:
[1]. Elgiushy HR, et al. Identification of a promising hit from a new series of pyrazolo[1,5-a]pyrimidine based compounds as a potential anticancer agent with potent CDK1 inhibitory and pro-apoptotic properties through a multistep in vitro assessment [published online ahead of print, 2022 Jan 29]. Bioorg Chem. 2022;120:105646.
[2]. Gangadevi S, et al. Kobophenol A Inhibits Binding of Host ACE2 Receptor with Spike RBD Domain of SARS-CoV-2, a Lead Compound for Blocking COVID-19. J Phys Chem Lett. 2021;12(7):1793-1802.
In Vitro, CDK1-IN-1 (compound 7a) (10 µM, 48 hours) has the high antiproliferative activity with a mean percentage of growth inhibition of 48.5 % over NCI cancer cell lines, and caused more than 40% growth inhibition in 36 cancer cell lines from different cancer subtypes[1]. CDK1-IN-1 (0.1-100 μM, 48 hours) has better selectivity for cancer cells over normal cell lines (IC50 of 17.7 and 6.28 μM in WI-38 and HCT-116 cells, respectively; SI=2.8)[1]. CDK1-IN-1 (17.7 μM in WI-38 and 6.28 μM in HCT-116; 48 hours) has a superior activity on cancerous cells than normal cells in inducing apoptosis and arresting the cell cycle at the G2/M phase[1]. CDK1-IN-1 (17.7 μM in WI-38 and 6.28 μM in HCT-116; 48 hours) can cause cell death mainly through apoptosis rather than necrosis and confirmed that its activity is more selective to cancerous cells than normal cells[1]. CDK1-IN-1 (6.28 μM; 48 hours) induce apoptosis in p53 dependent manner through the intrinsic apoptotic pathway in HCT-116 cells[1].
References:
[1]. Elgiushy HR, et al. Identification of a promising hit from a new series of pyrazolo[1,5-a]pyrimidine based compounds as a potential anticancer agent with potent CDK1 inhibitory and pro-apoptotic properties through a multistep in vitro assessment [published online ahead of print, 2022 Jan 29]. Bioorg Chem. 2022;120:105646.
[2]. Gangadevi S, et al. Kobophenol A Inhibits Binding of Host ACE2 Receptor with Spike RBD Domain of SARS-CoV-2, a Lead Compound for Blocking COVID-19. J Phys Chem Lett. 2021;12(7):1793-1802.