CDK9 inhib 
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  • ||||||||||  Journal:  CDK9 targeting PROTAC L055 inhibits ER?-positive breast cancer. (Pubmed Central) -  Jul 28, 2024   
    Additionally, L055 suppressed the growth of organoids and tumors derived from T47D and MCF7 cells in nude mice. Thus, L055 represents a potential novel therapeutic agent for ER?-positive breast cancer and potentially other malignancies.
  • ||||||||||  alvocidib (DSP-2033) / Sumitomo Pharma
    Journal:  Uncovering potential CDK9 inhibitors from natural compound databases through docking-based virtual screening and MD simulations. (Pubmed Central) -  Jul 16, 2024   
    The first-generation CDK inhibitor Flavopiridol was used as a reference to compare with our novel hit compound as a CDK9 antagonist...They also showed reasonable figures in the predicted absorption, distribution, metabolism, excretion, and toxicity (ADMET) calculations as well as in computational cytotoxicity predictions. Therefore, we anticipate that the proposed scaffolds could contribute to developing potential and selective CDK9 inhibitors subjected to further validations.
  • ||||||||||  Journal:  An enhancer RNA recruits KMT2A to regulate transcription of Myb. (Pubmed Central) -  Jun 18, 2024   
    Myrlin CRISPRi compromised KMT2A occupancy in the Myb locus, decreasing CDK9 and RNA Pol II binding and resulting in Pol II pausing in the Myb first exon/intron. Thus, Myrlin directly participates in activating Myb transcription by recruiting KMT2A.
  • ||||||||||  Journal:  Discovery of novel CDK9 inhibitor with tridentate ligand: Design, synthesis and biological evaluation. (Pubmed Central) -  Jun 16, 2024   
    Research on the mechanism indicated that Z4-7a could induce apoptosis in the HCT116 cell line by inhibiting phosphorylation of RNA polymerase II at Ser2, which resulted in the inhibition of apoptosis-related genes and proteins expression. In brief, introduction of tridentate ligand might work as a promising strategy for the development of novel selective CDK9 inhibitor.
  • ||||||||||  Venclexta (venetoclax) / Roche, AbbVie, alvocidib (DSP-2033) / Sumitomo Pharma
    Journal, IO biomarker:  Myeloid Targeted Human MLL-ENL and MLL-AF9 Induces cdk9 and bcl2 Expression in Zebrafish Embryos. (Pubmed Central) -  Jun 13, 2024   
    In addition, cotreatment with Venetoclax and Flavopiridol significantly reduced the expression of endogenous mcl1a compared to vehicle, consist with AML. This new model of MLL-r-AML provides a novel tool to understand the molecular mechanisms underlying disease progression and a platform for drug discovery.
  • ||||||||||  Journal:  Structure-guided design and cloning of peptide inhibitors targeting CDK9/cyclin T1 protein-protein interaction. (Pubmed Central) -  May 29, 2024   
    While these results demonstrate the promise of the designed peptides as blockers of CDK9 with high affinity, additional experimental studies are required to validate their biological activity and assess their selectivity. Such investigations will provide valuable insights into their therapeutic potential and pave the way for the future development of peptide-based inhibitors targeting the CDK9-cyclin T1 complex.
  • ||||||||||  dinaciclib (MK-7965) / Merck (MSD)
    Preclinical, Journal:  Impact of CDK Inhibitors on TBXT Expression in Chordoma Cell Lines Including the First Stable Cell Line of a High-Grade Chordoma. (Pubmed Central) -  May 24, 2024   
    CDK7 and CDK9 inhibition was lately identified as being effective in reducing viability in four chordoma cell lines, most likely due to a reduction in brachyury levels. In this study, we determined the capability of the CDK7 inhibitor THZ1 and the CDK1/2/5/9 inhibitor dinaciclib to reduce TBXT expression at mRNA and protein levels in a broad range of nine cell lines that are models of primary, recurrent, and metastasised chordoma of the clivus and the sacrum.
  • ||||||||||  dinaciclib (MK-7965) / Merck (MSD)
    Journal:  CDK9 inhibition as an effective therapy for small cell lung cancer. (Pubmed Central) -  May 20, 2024   
    As CDK9 and IRS inhibitors have already entered human clinical trials for cancer treatment, these findings provide comprehensive preclinical support for developing trials for Hh-driven cancers. Treatment-na
  • ||||||||||  Review, Journal:  Focus on current and emerging treatment options for glioma: A comprehensive review. (Pubmed Central) -  May 1, 2024   
    Despite promising preclinical data, the monoclonal antibody Depatuxizumab has proven ineffective in glioblastoma treatment, emphasizing the critical need to understand resistance mechanisms...In addition to advancements in cancer vaccine development, this review highlights the evolving landscape of LGG treatment, emphasizing a shift toward personalized and targeted therapies. Ongoing research is essential for refining strategies and enhancing outcomes in the management of LGG.
  • ||||||||||  Journal:  CDK9 inhibition activates innate immune response through viral mimicry. (Pubmed Central) -  Apr 25, 2024   
    Overall, our data suggest that EXOs derived from primary CSPCs hold great therapeutic potential for treating cartilage defect-associated disorders such as degenerative OA, and that CDK9 is a key factor in this process. We propose that it is possible to induce similar effects in patients using CDK9 inhibition, which, we show, causes DNA damage in
  • ||||||||||  Journal:  Novel agents and regimens in relapsed or refractory peripheral T-cell lymphoma: latest updates from 2023 ASH annual meeting. (Pubmed Central) -  Apr 23, 2024   
    Notably, the emergence of innovative therapeutic agents and regimens holds promise for durable responses and improved survival for patients with R/R PTCL. We summarize recent advances in the treatment of R/R PTCL from the 2023 ASH Annual Meeting, highlighting novel agents targeting EZH1/2, JAK1, PI3K, KIR3DL2, CD38/CD3xCD28, or CDK9, as well as therapeutic regimens in combination with stem cell transplantation, immunomodulators, epigenetic modifying agents, or CD30/CD16A bispecific antibodies.
  • ||||||||||  Journal:  Transcription bodies regulate gene expression by sequestering CDK9. (Pubmed Central) -  Apr 18, 2024   
    Overexpression of CDK9 in wild-type embryos results in the formation of ectopic transcription bodies and thus phenocopies the removal of the two large transcription bodies. Taken together, our results show that transcription bodies regulate transcription by sequestering machinery, thereby preventing genes elsewhere in the nucleus from being transcribed.
  • ||||||||||  zotiraciclib (TG02) / Cothera Biosci
    Review, Journal:  Recent Discovery and Development of Inhibitors that Target CDK9 and Their Therapeutic Indications. (Pubmed Central) -  Apr 12, 2024   
    Several potent small molecule inhibitors, exemplified by TG02 (4), have progressed to clinical trials...Our focus extends to various types of inhibitors, including pan-inhibitors, selective inhibitors, dual-target inhibitors, degraders, PPI inhibitors, and natural products. The discussion encompasses chemical structures, structure-activity relationships (SARs), biological activities, selectivity, and therapeutic potential, providing detailed insight into the diverse landscape of CDK9 inhibitors.
  • ||||||||||  JQ-1 / Roche
    Journal:  Transcriptional elongation control of hypoxic response. (Pubmed Central) -  Apr 6, 2024   
    We demonstrate that BRD4 bromodomains (BET) are dispensable for the release of paused RNAPII at hypoxia-activated genes and that BET inhibition by JQ1 is insufficient to impair hypoxic gene response...PAF1C disruption using a small-molecule inhibitor (iPAF1C) impairs hypoxia-induced, BRD4-mediated RNAPII release. Together, our results provide insight into potentially targetable mechanisms that control the hypoxia-responsive transcriptional elongation.
  • ||||||||||  Journal:  Actin associates with actively elongating genes and binds directly to the Cdk9 subunit of P-TEFb. (Pubmed Central) -  Apr 3, 2024   
    Supporting the specific role for actin in the elongation phase of transcription, chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) reveals that actin interacts with genes only upon their active transcription elongation. This study therefore provides novel insights into the mechanisms by which actin facilitates the transcription process.
  • ||||||||||  TT001 / Ting Therap
    Journal:  Identification of a Novel Selective CDK9 Inhibitor for the Treatment of CRC: Design, Synthesis, and Biological Activity Evaluation. (Pubmed Central) -  Mar 29, 2024   
    In this work, we preliminarily demonstrated the feasibility of CDK9 as a potent target of treatment for colorectal cancer, and a series of novel CDK9 inhibitors were rationally designed and synthesized based on the structure of AZD5438 (a pan CDKs inhibitor reported by AstraZeneca)...Research on the mechanism indicated that CLZX-205 could induce apoptosis in the HCT116 cell line by inhibiting phosphorylation of RNA polymerase II at Ser2, which resulted in the inhibition of apoptosis-related genes and proteins expression, and these results were validated at the cellular and tumor tissue levels. Currently, CLZX-205 is undergoing further research as a promising candidate for CRC treatment.
  • ||||||||||  Borrowing transcriptional kinases using chemically induced proximity | Poster Board #1900 (In-person; Poster Board #1900; Hall C (Ernest N. Morial Convention Center)) -  Mar 12, 2024 - Abstract #ACSSp2024ACS_Sp_3004;    
    Lastly, this concept led to the development of CDK-TCIP3, which rewires CDK12/13 to induce cell death in SUDHL5 cells (595 nM) and activation in the BCL6-driven GFP reporter cells. These bivalent CDK-TCIPs show that transcriptional machinery can be rewired using ATP-competitive ligands.
  • ||||||||||  Venclexta (venetoclax) / Roche, AbbVie, barasertib-HQPA (AZD2811) / AstraZeneca, AZD4573 / AstraZeneca
    Proteomic evaluation of combination data in acute myeloid leukemia to inform mechanism of action and new targets (Section 20) -  Mar 5, 2024 - Abstract #AACR2024AACR_9053;    
    In the proteomics evaluation study, MOLM13 cells treated for 7 days under different conditions - (1) vehicle control; (2) cytarabine alone; (3) decitabine alone; (4) venetoclax alone; (5) AZD4573 alone; (6) AZD4573+cytarabine; (7) AZD4573+decitabine; (8) AZD4573+venetoclax - were collected for proteomics analysis using LC-MS/MS...Interestingly, targeting AURKB with AZD2811 has been shown to overcome venetoclax resistance in AML... Our proteomics analysis identifies vulnerable and resistant pathways and proteins, shedding light on the mechanism of action and revealing potential new targets for AML.
  • ||||||||||  AZD8421 / AstraZeneca
    Targeting the cell cycle with AZD8421, a potent and highly selective CDK2 inhibitor (Section 18) -  Mar 5, 2024 - Abstract #AACR2024AACR_8375;    
    Monotherapy activity and combination benefit in vivo with standard of care agents was also observed in ovarian PDX models with elevated levels of CCNE1. AZD8421 is a potent and highly selective CDK2 inhibitor, with double digit nM potency in cells, as well as suitable physical and pharmacokinetic properties for progression into the clinic.