alvocidib (DSP-2033)

Pharmacological screening further identified distinct therapeutic vulnerabilities, demonstrating distinct subtype-specific sensitivity of MYCN-driven cells to transcriptional inhibitors (THZ1, Flavopiridol) and the cell-cycle inhibitor Volasertib, indicative of a unique oncogene-addicted state compared to RB1-deficient retinoblastoma cells. Collectively, our study elucidates the developmental and molecular mechanisms underpinning MYCN-driven retinoblastoma, establishes a robust and clinically relevant human retinal organoid platform, and highlights targeted transcriptional inhibition as a promising therapeutic approach for this aggressive pediatric cancer subtype.

We also examine structures affected by a transcription inhibitor, flavopiridol...Along with a reduction in peroxisome function, dissociation of peroxisome pore proteins PEX13 and PEX14 was detected by STORM microscopy. We conclude that SEC-MS combined with crosslinking is a valuable method to detect and quantify drug or disease effects on subcellular structures and may shed light on new aspects to mechanisms underlying their biologic outcomes.

The CDK9/T1 inhibition study indicates that a piperidine ring at the C8 position of the chromone nucleus is crucial, as C6-regioisomers show significantly reduced or no inhibition. The developed method for producing clinically important piperidine alkaloids is straightforward, is scalable, and involves only a few chromatographic purification steps.

Inhibition of STAT1 phosphorylation with fludarabine and flavopiridol enhanced PLT generation, uncovering a novel role in platelet generation beyond their established functions in cell cycle arrest and apoptosis. In conclusion, our findings unveil the modulating roles of immune and senescence signaling in imMKCLs to optimize cell and culture conditions for large-scale PLT manufacturing.

Current clinical evidence, including a phase II trial of flavopiridol in advanced RCC, highlights the potential but also the need for further validation. In conclusion, flavonoids offer a promising approach to improving RCC treatment. Future research should focus on optimizing their therapeutic efficacy and ensuring their safe clinical translation, with the goal of achieving personalized and minimally invasive cancer therapies.

Molecular docking simulations evaluated CDK1's binding affinity with pharmacologically active compounds (alvocidib, seliciclib, alsterpaullone) using AutoDock Vina. The enzyme's dual role in driving tumor progression and reshaping the immune microenvironment positions it as a promising therapeutic target. Computational validation of CDK1 inhibitors provides a rational basis for developing precision therapies against LF-HCC, bridging translational gaps between biomarker discovery and clinical application.

IGF2BPs exhibit significantly high expression in most tumors and are associated with prognosis, pathological stage, mutational status, methylation levels, and the relevant indicators of immunotherapy sensitivity in multiple tumors. Moreover, IGF2BPs may play an oncogenic role by activating common signaling pathways. Therefore, IGF2BPs may be potential prognostic markers for tumor therapy and targets for immunotherapy and drug therapy.

Notably, combining NCAPH knockdown with an mTOR inhibitor (Everolimus) or a cyclin-dependent kinase inhibitor (Flavopiridol) demonstrated promising anti-tumor effects both in vitro and in vivo. This study highlights the significant pro-tumor role of NCAPH in PCa and suggests its potential as a therapeutic target.

FP reduced cell proliferation and induced apoptosis by inducing mitochondrial dysfunction and oxidative stress, as well as increasing BAX/BCL2 and pCDK1 levels. These results suggest that toxicity to the reproductive system should be considered when FP is used in clinical applications.

Our results indicated that dinaciclib and alvocidib exhibited similar activity and sensitivity in the neuroendocrine cluster. Also, a lineage factor named KLF5 recognized by inferred transcriptional factors activity could be suppressed by verteporfin.

PAAD with high MCM3 expression was sensitive to c-75, brivanib, flavopiridol and VNLG/124 drugs, with stable molecular docking models. MCM3 is likely to be a critical element in promoting the initiation and growth of PAAD. Flavopiridol may exert its anti-PAAD effect through the interaction between MCM3, classic CDK1 targets in the cell cycle checkpoint and p53 pathway as well as related molecules in other pathways.

In the mouse model of diet-induced obesity, flavopiridol attenuated obesity-associated adipose tissue inflammation and improved serum lipid profile, glucose tolerance as well as insulin sensitivity. In conclusion, the FDA approved drug flavopiridol could be placed as a potential drug candidate for the treatment of cancer and obesity comorbid patients.