CDK9 inhib 
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  • ||||||||||  Journal:  Discovery of SHR5428 as a Selective and Noncovalent Inhibitor of CDK7. (Pubmed Central) -  Aug 21, 2023   
    Furthermore, the computational modeling has shed some light on this mechanism. Additionally the in vivo efficacy study in a breast cancer cell line (HCC70 cell) derived xenograft mouse model proved SHR5428 to be orally efficacious with dose-dependent tumor growth inhibition.
  • ||||||||||  JQ-1 / Roche
    Journal:  Distinct layers of BRD4-PTEFb reveal bromodomain-independent function in transcriptional regulation. (Pubmed Central) -  Aug 21, 2023   
    Although BRD4-PTEFb can associate with chromatin through acetyl recognition, our results indicate that a distinct, active BRD4-PTEFb population functions to regulate transcription independently of bromodomain-mediated chromatin association. These findings may enable more effective pharmaceutical modulation of BRD4-PTEFb activity.
  • ||||||||||  OVEREXPRESSION OF CYCLIN DEPENDENT KINASES AND CYCLINS ACROSS SARCOMAS BEYOND CDK4 (The Liffey, Level 1) -  Aug 16, 2023 - Abstract #CTOS2023CTOS_549;    
    25% of cases above that threshold we accurately identified known associations between CDK4/LPS and CCND1/Ewing sarcoma while also revealing new associations. The most notable overexpressers were chordoma (CDK7, CDK18), CCS (CDK2, CCNA1), RCS (CCND2), and RMS (CDK6, CDK8, CCND2, CCNE1).
  • ||||||||||  enitociclib (VIP152) / Vincerx
    Journal, IO biomarker:  CDK9 INHIBITORS: a promising combination partner in the treatment of hematological malignancies. (Pubmed Central) -  Aug 12, 2023   
    In its first in-human trial, enitociclib demonstrated clinical activity in a small cohort of patients with high grade B lymphoma with MYC and BCL2 and/or BCL6 rearrangements, inducing complete responses in 2 of 7 subjects (29%) in monotherapy. These data suggest CDK9 inhibitors could play a role in the treatment of hematological diseases and could be a great ally when combined with other therapeutic approaches.
  • ||||||||||  Review, Journal:  Cyclin-dependent kinase-9 in B-cell malignancies: pathogenic role and therapeutic implications. (Pubmed Central) -  Aug 8, 2023   
    Early phase clinical trials established safety of CDK9 inhibitors, with manageable neutropenia, infections and gastrointestinal toxicities. In this review, we summarize the rationale of targeting CDK9 in lymphoid malignancies, as well as pre-clinical and early clinical data with pan-CDK and selective CDK9 inhibitors.
  • ||||||||||  JQ-1 / Roche
    Journal:  Quantitative Proteomics of the CDK9 Interactome Reveals a Function of the HSP90-CDC37-P-TEFb Complex for BETi-Induced HIV-1 Latency Reactivation. (Pubmed Central) -  Aug 4, 2023   
    Upon treatment with the selective BET bromodomain inhibitor JQ1, 352 proteins were successfully identified with high confidence as CDK9-interacting proteins...Furthermore, the HSP90-CDC37-P-TEFb complex directly regulates HIV-1 transcription and relies on recruitment by heat shock factor 1 (HSF1) for binding to the HIV-1 promoter. These results advance the understanding of HSP90-CDC37-P-TEFb in HIV-1 latency reversal and enlighten the development of potential strategies to eradicate HIV-1 using a combination of targeted drugs.
  • ||||||||||  AT7519 / Novartis, Otsuka
    Journal:  Examination of the Impact of Triazole Position within Linkers on Solubility and Lipophilicity of a CDK9 Degrader Series. (Pubmed Central) -  Jul 19, 2023   
    Using chromatographic logD and kinetic solubility experiments, we show that degraders with similar chemical constitution but varied position of the embedded triazole demonstrate different lipophilicity and aqueous solubility properties. Overall, this work highlights the impact of triazole placement on linker composition through application of click chemistry for degrader synthesis and its ability to be used to promote the achievement of favorable physicochemical properties.
  • ||||||||||  Journal:  Biomimetic black phosphorus nanosheets codeliver CDK9 and BRD4 inhibitors for gastric cancer targeted therapy. (Pubmed Central) -  Jul 7, 2023   
    The tumor growth monitoring demonstrated that the combination of CI and BI codelivered by M@BP significantly inhibited the tumor progress than the single inhibitors, and the inhibition effect could be further enhanced upon NIR irradiation. Taken together, M@BP with tumor-targeting capacity and high drug loading efficiency for CI and BI could efficiently block the activation of CDK9 and BRD4, exhibiting excellent antitumor activity under NIR irradiation without systemic toxicity in an orthotopic GC model.
  • ||||||||||  Journal:  An Overview of CDK Enzyme Inhibitors in Cancer Therapy. (Pubmed Central) -  Jun 19, 2023   
    CDKIs are CDK4/6, CDK7, CDK9, and CDK12 inhibitors. Finally, we have looked into the efficacy of CDK inhibitors and PD1/PDL1 antibodies when used together, which could lead to the development of a viable cancer treatment strategy.
  • ||||||||||  Journal, Tumor mutational burden, PD(L)-1 Biomarker, IO biomarker:  Prolonged Survival of NUT Midline Carcinoma and Current Approaches to Treatment. (Pubmed Central) -  Jun 13, 2023   
    RNA sequencing of this patient's tumor demonstrated overexpression of multiple potentially targetable genes. Given the altered transcription that results from the causative mutation multi-omic evaluation of these tumors may uncover druggable targets for treatment.
  • ||||||||||  Targeting cyclin-dependent kinase 9 to control lethal prostate cancer (Poster and Exhibition Hall) -  Jun 13, 2023 - Abstract #EACR2023EACR_1120;    
    These changes reveal both adaptive and detrimental responses, and identify actionable combinatoric lethal targets. Integrating genetic information from the patient's tumor may enable discovery of actionable synthetic lethal interactions.ConclusionCompounds targeting CDK9 elicit comprehensive rewiring of prostate cancer cells and provide a candidate treatment strategy against CRPC.
  • ||||||||||  dinaciclib (MK-7965) / Ligand, Merck (MSD)
    Dinaciclib as an effective treatment for Small Cell Lung Cancer (Poster and Exhibition Hall) -  Jun 13, 2023 - Abstract #EACR2023EACR_701;    
    Integrating genetic information from the patient's tumor may enable discovery of actionable synthetic lethal interactions.ConclusionCompounds targeting CDK9 elicit comprehensive rewiring of prostate cancer cells and provide a candidate treatment strategy against CRPC. Introduction Treatment-na
  • ||||||||||  KB-0742 / Kronos Bio, enitociclib (VIP152) / Vincerx, fadraciclib (CYC065) / Cyclacel
    Review, Journal:  Targeting CDK9 with selective inhibitors or degraders in tumor therapy: an overview of recent developments. (Pubmed Central) -  Jun 9, 2023   
    Only VIP152 has been proven to benefit the patients with advanced high-grade lymphoma (HGL) and solid tumors in clinical trials. Continued efforts to explore the molecular mechanisms underlying the inhibitory effects, and to identify suitable tumor genotypes and combination treatment strategies, are crucial to demonstrate the efficacy of selective CDK9 inhibitors and degraders in tumor therapy.
  • ||||||||||  sevoflurane / Generic mfg.
    Journal:  Sevoflurane-induced P300 promotes neuron apoptosis via Sp1/SDK9 pathway. (Pubmed Central) -  Jun 5, 2023   
    Mice exposed to sevoflurane using P300 inhibitor also showed decreased levels of apoptosis of cortical cells and a decrease in recent cognitive impairment. In summary, sevoflurane-induced P300 inhibited activity of Sp1 by increasing Sp1 acetylation modification, down-modulates CDK9 expression, and promotes the occurrence of neuronal apoptosis.
  • ||||||||||  Journal:  Study on the Mechanism of MC5R Participating in Energy Metabolism of Goose Liver. (Pubmed Central) -  May 31, 2023   
    In addition, PPI analysis suggests that the selected downstream genes, including GYS2, ECI2, PSPH, CPT1A, ACSL1, HMGCS1, USP25 and NDRG1, participate in the protein-protein interaction network regulated by MC5R. In conclusion, MC5R may mediate the biological effects caused by changes in nutrition and energy levels in goose hepatocytes through multiple pathways, including glycolipid-metabolism-related pathways.
  • ||||||||||  Review, Journal:  A patent review of selective CDK9 inhibitors in treating cancer. (Pubmed Central) -  May 29, 2023   
    CDK9 inhibitors with short half-life and intravenous administration might result in transient target engagement and contribute to a better safety profile in vivo. However, more efforts are urgently needed to accelerate the development of CDK9 inhibitors, including the research on new binding modes between ligand and receptor or new protein binding sites.
  • ||||||||||  Journal:  The NELF pausing checkpoint mediates the functional divergence of Cdk9. (Pubmed Central) -  May 17, 2023   
    Upon inhibition of Cdk9, cells with NELF efficiently shutdown gene transcription, while in NELF-depleted cells, defective, non-productive transcription continues unabated. By introducing a strict checkpoint for Cdk9, the evolution of NELF was likely critical to enable increased regulation of Cdk9 in higher eukaryotes, as Cdk9 availability can be restricted to limit gene transcription without inducing wasteful, non-productive transcription.
  • ||||||||||  Journal:  Isobaric Stable Isotope N-Phosphorylation Labeling (iSIPL) for Ultrasensitive Proteome Quantification. (Pubmed Central) -  May 15, 2023   
    The interaction of CDK9 with PARP13 was found to significantly decrease during Tat-induced activation of HIV-1 gene transcription, suggesting the effectiveness of iSIPL strategy in dynamic analysis of protein-protein interaction in vivo. More than that, the proposed iSIPL strategy would facilitate large-scale accurate quantitative proteomics by increasing multiplexing capability.
  • ||||||||||  Journal:  7SK methylation by METTL3 promotes transcriptional activity. (Pubmed Central) -  May 14, 2023   
    7SK methylation enhanced its binding to heterogeneous nuclear ribonucleoproteins, causing the release of the HEXIM1 P-TEFb complex subunit1 (HEXIM1)/P-TEFb complex and inducing transcriptional elongation. Our findings establish the mechanism underlying 7SK activation and uncover a previously unknown function for the mA modification in converting growth factor signaling events into a regulatory transcriptional response via an RNA methylation-dependent switch.
  • ||||||||||  Journal:  Sirtuin 6 is required for the integrated stress response and resistance to inhibition of transcriptional cyclin-dependent kinases. (Pubmed Central) -  May 7, 2023   
    In human PDAC cell lines and organoids as well as in murine PDAC genetically engineered mouse models where SIRT6 was deleted or down-regulated, we demonstrated that SIRT6 loss both defined the basal PDAC subtype and led to reduced ATF4 protein stability and a nonfunctional ISR, causing a marked vulnerability to CDK7 and CDK9 inhibitors. Thus, we have uncovered an important mechanism regulating a stress-induced transcriptional program that may be exploited with targeted therapies in particularly aggressive PDAC.
  • ||||||||||  Journal:  m A promotes planarian regeneration. (Pubmed Central) -  May 7, 2023   
    Intriguingly, the depletion of m A-modified transcripts grn, cdk9 or cdk7 partially rescues the defective regeneration of planarian caused by wtap knockdown. Overall, our study reveals an indispensable role of m A modification in regulating whole-organism regeneration.
  • ||||||||||  Venclexta (venetoclax) / Roche, AbbVie, Walter and Eliza Hall Institute, dinaciclib (MK-7965) / Ligand, Merck (MSD)
    Preclinical, Journal:  Venetoclax and dinaciclib elicit synergistic preclinical efficacy against hypodiploid acute lymphoblastic leukemia. (Pubmed Central) -  May 3, 2023   
    This combination eradicated leukemic blasts within hypodiploid ALL PDX mice with low off-target toxicity. Our findings suggest that dual inhibition of BCL-2 (venetoclax) and CDK9/MCL-1 (dinaciclib) is a promising therapeutic approach in hypodiploid ALL, warranting further investigation to inform clinical trials in this high-risk patient population.