Enitociclib also potentiates the cytotoxicity of venetoclax in relatively venetoclax-resistant KMT2A-r leukemic cells. Overall, enitociclib has shown measurable in vitro antitumor activity in KMT2A-r infant leukemia and is a rational therapeutic option to explore in future clinical trials.

To obtain CDK9 inhibitors with high activity and safety, we designed and synthesized a series of sulfonamide derivatives as CDK9 inhibitors based on BAY1143572, the first selective CDK9 inhibitor to enter clinical trials...Further studies showed that L18 possessed moderate metabolic properties and exhibited an in vivo safety profile superior to that of the positive control. This study provides a potential lead compound for the development of CDK9 inhibitors for cancer therapy.

These effects were recapitulated by the CDK9-selective inhibitor enitociclib, which downregulated TFE3 targets and suppressed tRCC cell growth. Our findings nominate CDK9 inhibition as a therapeutic strategy in tRCC and demonstrate the utility of mechanism-informed phenotypic screening for challenging targets.

CDK9 inhibitors show promising activity against patient-derived models of CRC. MAPK signaling is particularly suppressed by CDK9 inhibitors. Combining CDK9 inhibitors and targeted therapy against MAPK signaling pathway may be a viable strategy worthy of further investigation preclinically and clinically.

We also showed that targeting CDK9 by AZD4573 and enitociclib is a safe and effective treatment in preclinical MCL models, supporting CDK9 as a valid therapeutic target for MCL. Furthermore, YX0798 has the potential to be used in combination therapy with clinical agents to improve treatment efficacy. Together, these data demonstrate that YX0798 has oral bioavailability, exquisite selectivity, and anti-tumor potency that results from driving transcription reprogramming towards tumor cell killing.

P1/2, N=8, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2025 --> Dec 2025

Additionally, enitociclib demonstrated synergistic effects with several anti-MM agents, including bortezomib, lenalidomide, pomalidomide, and venetoclax. These results suggest that enitociclib may represent a promising therapeutic option for the treatment of MM, either as a single agent or in combination with other anti-MM agents.

Among them, compound 24 displayed the best antiproliferative activity against MOLM-13 cells with an IC50 value of 0.034 μM, which was comparable to the positive drug (BAY1251152, IC50 = 0.031 μM)...Finally, further studies of compound 24 about molecular docking, molecular dynamics simulations and ADMET prediction were investigated. Collectively, compound 24 deserves further structural optimization and development for the treatment of acute myeloid leukemia.

P1/2, N=8, Active, not recruiting, National Cancer Institute (NCI) | N=130 --> 8 | Trial completion date: Jul 2029 --> Jun 2025

P1/2, N=130, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2025 --> Jul 2029 | Trial primary completion date: Mar 2025 --> Jul 2024

P1/2, N=130, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting

P1, N=110, Completed, Vincerx Pharma, Inc. | Active, not recruiting --> Completed