alvocidib (DSP-2033) / Sumitomo Pharma - LARVOL DELTA

Integrative multi-omics profiling of a self-established cohort reveals metabolic reprogramming networks in rheumatoid arthritis. (PubMed, J Pharm Biomed Anal) - "Several compounds, including flavopiridol hydrochloride, serine, diclofenac, and carbamazepine, may serve as potential modulators of RA-associated metabolic remodeling. Unlike previous studies limited to single-omics data, our integrative analysis of proteomics, phosphoproteomics, and transcriptomics systematically delineates metabolic regulatory networks in RA immune cells and identifies novel candidate targets, thereby offering new mechanistic insights and potential directions for therapeutic intervention."

Journal • Immunology • Inflammation • Inflammatory Arthritis • Metabolic Disorders • Rheumatoid Arthritis • Rheumatology • NFKB2 • NPM1 • STAT1 • STAT2

Development and validation of a novel LC-MS/MS method for simultaneous quantification of alvocidib and its glucuronide: application to pharmacokinetic and tissue distribution study in rats. (PubMed, Anal Methods) - "In contrast, Alv-G showed the highest distribution in the small intestine and the lowest amount in the colon compared to the other tissues. This method is applicable for PK and tissue distribution studies to quantify both alvocidib and its glucuronide."

Journal • PK/PD data • Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Comparative study on the inhibitory potential of anticancer drugs and natural compounds against PHB proteins. (PubMed, Nat Prod Res) - "Six top candidates Ibrutinib, Daunorubicin, Doxorubicin, Rutin, Flavopiridol, and Camptothecin exhibited binding affinities ranging from -9.7 to -10.5 kcal/mol. These findings position Ibrutinib as a promising PHB-targeting agent for cancer therapy. Further in vitro and in vivo validations are essential to confirm its therapeutic potential."

Journal • Oncology

Human Retinal Organoid Modeling Defines Developmental Window and Therapeutic Vulnerabilities in MYCN-Amplified Retinoblastoma. (PubMed, Int J Mol Sci) - "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."

Journal • Eye Cancer • Oncology • Pediatrics • Retinal Disorders • Retinoblastoma • Solid Tumor • MYCN • RB1 • SOX2

Repurposing flavopiridol as an inhaled therapeutic for pulmonary fibrosis. (PubMed, Eur J Pharmacol) - "In a bleomycin-induced mouse model of lung fibrosis, systemic administration of flavopiridol improved survival, attenuated body weight loss, and reduced fibrotic lesions and collagen deposition, outperforming the FDA-approved drug nintedanib. Further, we developed an inhalable formulation of flavopiridol and demonstrated its efficacy in mitigating fibrosis through local lung delivery, which minimized systemic drug exposure and potential adverse effects. These findings establish CDK9 as a critical regulator of lung fibrosis and provide compelling evidence for developing CDK9 inhibitors as novel therapeutic agents for IPF."

Journal • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Global Profiling of Remodeled Subcellular Structures Due to Drug Treatment and Disease. (PubMed, bioRxiv) - "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."

Journal • Ewing Sarcoma • Oncology • Sarcoma • Solid Tumor • PEX13

Total Synthesis of Rohitukine and Dysoline and Their Anticancer Analogues Flavopiridol and IIIM-290. (PubMed, ACS Omega) - "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."

Journal • Oncology • CDK9

Endogenous Real Time Imaging Reveals Dynamic Chromosomal Mobility During Ligand-Mediated Transcriptional Burst Events. (PubMed, bioRxiv) - "Consistent with this, blocking transcription with flavopiridol shifts DNA tracks into a non-confined state. Differential DNA kinetics during burst vs non-burst has provided a strategy to assess altered condensate formation during gene activation events. (165)."

Journal • ER

EFFICACY AND OUTCOMES OF NOVEL THERAPEUTIC AGENTS AS MONOTHERAPY OR IN COMBINATION WITH CONVENTIONAL THERAPY IN ACUTE MYELOID LEUKEMIA: A SYSTEMATIC REVIEW AND META-ANALYSIS (EHA 2025) - "Agents included Guadectiabine 28%, Magrolimab 7% Alvocidib 3%, Enasidenib 23%,, Flotetuzumab 4%, Vadastuximab 9%, Mitoxantrone 9%, Pevonedistat 2%, Entospletinib 3%, Eprenetapopt 20%, Belinostat 0.5%, Onvansertib 3%, Panobinostat 2%, Cediranib Maleate 1%, Nilotinib 2%, Emavusertib 0.5%, and anti-CD45 antibody (DOTA-BC8) 0.5%. The conventional therapies were azacitidine 20% and cytarabine 17%... This study shows the promising efficacy of novel agents in AML and highlights the need for further prospective trials with larger patient populations to better understand the efficacy and safety outcomes of these agents in patients with AML."

Combination therapy • Monotherapy • Retrospective data • Review • Acute Myelogenous Leukemia • Anemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Oncology • Thrombocytopenia • TP53

DRUG SCREENING IN A ZEBRAFISH MODEL OF MLL-AF9-DRIVEN ACUTE MYELOID LEUKEMIA (EHA 2025) - "Control and MA9/lyz-EFGP ZF 48 hpf embryos were treated with 10 µM of daunorubicin, doxorubicin, cytarabine, or Venetoclax, and 6 µM of flavopiridol... In summary, our results show that our platform is capable of identifying drugs and drug combinations that show potential in treating AML. We are already in the process of testing several drugs approved for various other indications for the potential utility in treating leukemia."

Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • KMT2A • MLLT3 • RUNX1

STAT1-mediated epigenetic regulation of LIN28A controls iPSC-derived platelet production through the let-7-RALB axis. (PubMed, Blood Adv) - "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."

Journal • Oncology • RALB • STAT1

Targeting Cyclin-Dependent Kinase 12 (CDK12) for Cancer Therapy: Structure-Based Discovery of Two Novel CDK12 Inhibitors In Silico Using Integrated Bioinformatics. (PubMed, OMICS) - "Moreover, flavopiridol, a known inhibitor of CDK12, was used to cross-check with the selected ligands to validate our findings...Finally, we suggest that ZINC 02096057 and ZINC 02094702 offer prospects as novel inhibitors of CDK12, which warrant further in vitro and in vivo studies. Cancer therapeutics specifically, and drug discovery more generally, stand to benefit from novel molecular leads for CDK12 inhibition."

Journal • Oncology

Natural Compounds in Cancer Therapy: Revealing the Role of Flavonoids in Renal Cell Carcinoma Treatment. (PubMed, Biomolecules) - "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."

Journal • Review • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • GPX4 • MIR21 • MIR324 • STAT3 • YAP1

Therapeutic Potential of Flavopiridol in the Suppression of Lung Fibrosis Via CDK9 Inhibition (ATS 2025) - "The CDK9 inhibitor flavopiridol was evaluated in vitro using IPF lung fibroblast cell lines and in vivo in a bleomycin-induced murine model of IPF...In a mouse model of lung fibrosis, systemic administration of flavopiridol attenuated body weight loss, improved survival rates, and reduced fibrotic lesions and collagen deposition, showing superior antifibrotic efficacy compared to the FDA-approved drug nintedanib... Our findings suggest that CDK9 serves as a critical regulator of fibrogenesis in IPF and that inhibiting CDK9 through the use of flavopiridol represents a promising therapeutic strategy. The formulation of a novel method for the pulmonary delivery of flavopiridol presents a potential targeted treatment approach for IPF."

Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Inflammation • Pneumonia • Pulmonary Disease • Respiratory Diseases

Identification of CDK1 as a Biomarker for the Treatment of Liver Fibrosis and Hepatocellular Carcinoma Through Bioinformatics Analysis. (PubMed, Int J Mol Sci) - "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."

Biomarker • Journal • Fibrosis • Hepatocellular Cancer • Immunology • Liver Cirrhosis • Oncology • Solid Tumor • CDK1

Discovery of flavopiridol as a noncovalent thioredoxin reductase inhibitor through in silico and in vitro approach. (PubMed, Int J Biol Macromol) - "Importantly, surface plasmon resonance (SPR) experiments validated the binding interaction between flavopiridol and TrxR. This study offers valuable insights into the identification and investigation of novel TrxR inhibitors, potentially enhancing the application of flavopiridol as a promising TrxR inhibitor."

Journal • Preclinical • Oncology

Modulation of the cell cycle and inhibition of histone deacetylases by small molecules increase recombinant adeno-associated virus productivity across different HEK293 cell lines. (PubMed, Biotechnol Prog) - "A DoE-based approach also revealed the potential for combining both molecules to enhance rAAV production, exhibiting an additive effect across three different HEK293 derivatives. Consequently, novel functions of M344 and Flavopiridol as enhancers of rAAV production were unraveled, which can be employed to enhance the accessibility of in vivo gene therapy applications."

Journal • Preclinical • Gene Therapies

A pan-cancer analysis reveals the oncogenic and immunological role of insulin-like growth factor 2 mRNA-binding protein family members. (PubMed, Discov Oncol) - "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."

IO biomarker • Journal • Pan tumor • Tumor mutational burden • Microsatellite Instability • Oncology • AMPK • IGF2BP1 • MSI • TMB

NCAPH Promotes the Proliferation of Prostate Cancer Cells Via Modulating the E2F1 Mediated PI3K/AKT/mTOR Axis. (PubMed, Int J Med Sci) - "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."

Journal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • E2F1 • NCAPH

Genomics-based approach to drug testing in novel patient-derived xenograft models of undifferentiated pleomorphic sarcoma (EORTC-NCI-AACR 2024) - "Alvocidib, abemaciclib, copanlisib and trametinib had the lowest average IC50 values (208 nM, 407 nM, 348 nM and 452 nM respectively). RPPAs to investigate the mechanism behind the synergy of trametinib and infigratinib in UPS cell lines and in vivo experiments aimed at comparison of trametinib and infigratinib combination and doxorubicin (standard of care) efficacy in UPS PDX models are ongoing. Conclusion Trametinib monotherapy or in combination with infigratinib represents a potential novel therapy for UPS patients."

Preclinical • Oncology • Sarcoma • Solid Tumor • Undifferentiated Pleomorphic Sarcoma

Co-Targeting BCL-2 and MCL1 (via CDK9) in Pre-Clinical Models of High-Risk Acute Lymphoblastic Leukemia (ASH 2024) - "Relapsed disease has poor prognosis, especially after immunotherapeutic approaches have failed, including blinatumomab (bispecific T cell engager BITE) and chimeric antigen receptor T-cell (CAR-T) therapy...Methods : Venetoclax, alvocidib, S63845 (MCL1i), dexamethasone and tyrosine kinase inhibitors (TKIs) were from Selleckchem...Conclusions : Simultaneous inhibition of BCL-2 and CDK9 represents an effective approach for targeting Ph+, KMT2AR and CD19-/- B-ALL without need for additional DNA-damaging chemotherapy or kinase inhibition. Taken together, this provides strong rationale for the clinical translation of venetoclax combined with alvocidib in patients with poor prognosis ALL, thereby offering a promising novel combination treatment for CAYA."

IO biomarker • Preclinical • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • BCL2 • CDK9 • KMT2A • PRKDC

Flavopiridol Restores Granulopoiesis in an Experimental Model of Severe Congenital Neutropenia (ASH 2024) - "These data provide insight into the mechanism of action of flavopiridol in rescuing defective granulopoiesis in CN. Thus, we described for the first time a therapy for CN with flavopiridol that could be potentially used to treat patients with different types of neutropenia."

Hematological Disorders • Neutropenia • Oncology • CD34 • CDK2 • CDK4 • CEBPA • ELANE • SRP54

Flavopiridol restores granulopoiesis in experimental models of severe congenital neutropenia. (PubMed, Mol Ther) - "Flavopiridol also restored granulopoiesis caused by diminished CEBPA expression, a known defective signaling molecule in CN. Thus, we described for the first time a potential therapy for CN with flavopiridol that could be potentially used to treat patients with different types of neutropenia."

Journal • Hematological Disorders • Neutropenia • CD34 • CEBPA • ELANE

Flavopiridol: a promising cyclin-dependent kinase inhibitor in cancer treatment. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "Future research efforts should focus on refining its therapeutic profile, minimizing toxicity, and investigating synergistic treatment combinations, including those with immunotherapy. Understanding the mechanisms of resistance and discovering predictive biomarkers will be crucial for its effective integration into clinical practice."

IO biomarker • Journal • Review • Hematological Malignancies • Leukemia • Oncology • Solid Tumor

Flavopiridol induces cell cycle arrest and apoptosis by interfering with CDK1 signaling pathway in human ovarian granulosa cells. (PubMed, Sci Rep) - "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."

Journal • Metabolic Disorders • Oncology • BAX • BCL2 • CDK1