Quest for discovering novel CDK12 inhibitor.

CDK12 is essential for cellular processes like RNA processing, transcription, and cell cycle regulation, inhibiting cancer cell growth and facilitating macrophage invasion. CDK12 is a significant oncogenic factor in various cancers, including HER2-positive breast cancer, Anaplastic thyroid carcinoma, Hepatocellular carcinoma, prostate cancer, and Ewing sarcoma. It is also regarded as a potential biomarker, emphasizing its broader significance in oncology.

Can the Bladder Itself "Measure" Volume, and Thereby Help to Determine When Initiation of Voiding Should Occur? ICI-RS 2024.

Aims: To answer the question of whether the bladder itself can to any extent control or modulate the initiation of voiding.

Methods: This subject was discussed at the International Consultation on Incontinence-Research Society (ICI-RS) 2024 conference in Bristol, UK in a proposal session.

Results: Cells in the bladder wall sense the local environment via a diverse array of ion channels and receptors which together provide input to motor-sensory and signal transduction mechanisms.

Cocaine-Induced DNA-Dependent Protein Kinase Relieves RNAP II Pausing by Promoting TRIM28 Phosphorylation and RNAP II Hyperphosphorylation to Enhance HIV Transcription.

Drug abuse continues to pose a significant challenge in HIV control efforts. In our investigation, we discovered that cocaine not only upregulates the expression of the DNA-dependent protein kinase (DNA-PK) but also augments DNA-PK activation by enhancing its phosphorylation at S2056. Moreover, DNA-PK phosphorylation triggers the higher localization of the DNA-PK into the nucleus.

New thiourea derivatives that target the episomal silencing SMC5 protein to inhibit HBx-dependent viral DNA replication and gene transcription.

Unlabelled: Antivirals such as nucleotide analogs (NAs) are potent inhibitors of hepatitis B virus (HBV) replication. However, NAs fail to diminish the signaling and mitogenic activities of the transactivator HBx protein. Earlier we have shown that thiourea derivative IR-415 (DSA-00) targeted HBx to down-regulate its target viral and host genes.