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

Flavopiridol inhibits proliferation and induces apoptosis of airway smooth muscle cells (ERS 2026) - "5. Conclusion Our findings suggest that Flavopiridol has the potential to restore the imbalance of proliferation and apoptosis of ASMCs in asthma."

IO biomarker • Asthma • Immunology • Respiratory Diseases • BAX • BCL2 • CASP3 • CCNB1 • CDK1

A Pathway to Chordoma Treatment: A Review on CDKN2A and Therapeutic Targeting. (PubMed, Cancers (Basel)) - "Preclinical studies in CDKN2A-deficient chordoma cell lines and patient-derived xenografts demonstrated sensitivity to cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, including palbociclib, flavopiridol, and abemaciclib. Combination strategies pairing palbociclib with buparlisib or rapamycin produced greater antitumor effects, particularly in p16^INK4A- and PTEN-deficient models...Preclinical data support CDK4/6 inhibition, particularly in biomarker-selected CDKN2A-deficient tumors, and suggest that combination approaches targeting complementary pathways such as PI3K/mTOR may further enhance therapeutic efficacy. Together, these findings support the clinical relevance of CDKN2A as both a prognostic biomarker and a promising therapeutic target in chordoma."

Journal • Review • Chordoma • Eye Cancer • Oncology • Osteosarcoma • Retinal Disorders • Solid Tumor • CDKN2A • PTEN

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

HIV-1 Tat forms a dissociable complex with 7SK snRNP and exhibits clade differences in reversing the sequestration of P-TEFb (AIDS 2026) - "The P-TEFb kinase inhibitor flavopiridol (FVP), known to rapidly dissociate P-TEFb from 7SK snRNP, induced efficient dissociation of Tat:P-TEFb from 7SK snRNP... Our studies suggest that A and CRF_AE Tat variants are suitable candidates for HIV latency reversal by virtue of their more superior incorporation into 7SK snRNP and interaction with P-TEFb. Contrary to the notion that entry of Tat into 7SK snRNP leads to a dead-end complex in which P-TEFb can no longer be availed for transcription, we also show that Tat:7SK is a functional intermediate in which Tat:P-TEFb can be released en bloc ."

Human Immunodeficiency Virus • Infectious Disease • HEXIM1

Patient-derived organoids guide personalized therapy for KRAS-mutant pancreatic cancer: synergistic MEK/mTOR inhibition and predictive chemotherapy responses. (PubMed, Front Immunol) - "The synergistic effects of the MEK inhibitor trametinib combined with the mTOR inhibitor AZD8055 or the pan-CDK inhibitor flavopiridol were evaluated in PDOs and validated in matched PDXs. We also validated PDOs in predicting clinical gemcitabine/paclitaxel (Gem/PTX) responses...The trametinib/AZD8055 combination is a promising precision therapeutic strategy, and PDOs can serve as a reliable tool to guide clinical therapy selection. Despite limitations such as small sample size, lack of tumor microenvironment and immune components in the model system, this work provides important preclinical evidence for the clinical translation of PDOs in the personalized therapy of PDAC."

Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CA 19-9 • KRAS

Integrin-binding sialoprotein as an extracellular matrix-associated independent prognostic biomarker in glioma. (PubMed, BMC Cancer) - "IBSP represents an independent prognostic biomarker associated with adverse outcomes in glioma. These findings provide insight into the molecular mechanisms underlying IBSP-associated glioma progression and highlight potential therapeutic targets that may contribute to improved clinical outcomes in patients with glioma."

Biomarker • Journal • Brain Cancer • Genito-urinary Cancer • Glioma • Oncology • Prostate Cancer • Solid Tumor • CASP4 • KYNU • SIGLEC9 • SLC16A3

Neuronal cells derived from iPSCs cell to evaluate neurotoxicity after 48 or 72 hours in high-through put screening format (AACR 2024) - "Bortezomib (proteasome inhibitor), gemcitabine (approved ovarian cancer treatment), ivermectin (parasitic diseases treatment), flavopiridol (approved CDKs inhibitors), SNS-032 (approved CDKs inhibitor), mefloquine (anti-malaria drug), digitonin (nonionic detergent) and tamoxifen (hormone receptor-positive breast cancer treatment). In conclusion, this panel is a good tool to anticipate possible neurotoxicity within the 3Rs respect. It can be used in early drug de-risking or neuroprotection screening, with the aim of preventing/reducing/curing neuropathy in at-risk populations."

Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Ovarian Cancer • Solid Tumor

Investigation of the Inhibitory Effects and Underlying Mechanisms of Vitexin Derivatives Targeting CDK1 in HCT Colorectal Cancer Cells. (PubMed, Chem Biol Drug Des) - "Molecular docking reveals strong binding affinity between M3 and CDK1 (Docking score -10.127), and molecular dynamics simulations confirm the stability of the M3-CDK1 complex with inhibitory effects comparable to flavopiridol (FP). Furthermore, M3 downregulates CDK1/cyclin B expression in HCT-116 cells (IC₅₀ = 9.83 ± 2.65 μM). M3 may suppress HCT-116 cell proliferation by targeting CDK1/cyclin B and inducing G₂/M phase arrest."

Journal • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor • CDK1

Flavopiridol inhibits cell proliferation, migration, and invasion via downregulation of FOXM1 in triple negative breast cancer (AACR 2024) - "Triple-negative breast cancer (TNBC) represent 15-20% of all breast cancers and is the subtype of breast cancer that is not responsive to targeted breast cancer treatments such as anti-estrogens (tamoxifen) or HER2 targeted antibodies due to the lack of ER, PR, and HER2 receptors...Although recently the FDA approved sacituzumab (govitecan), a Trop-2-receptor directed antibody conjugated with chemotherapeutic agent topoisomerase inhibitor in metastatic TNBC, and response rate was 30% and the median duration of response is 7.7 months, and the majority of patients did not maintain response longer than 12 months...We are currently testing favopridol in MDA-MB-231 (human) and 4T1 mouse mammary) TNBC tumor models. In conclusion, our studies suggest that flavopiridol is a highly potent FOXM1 inhibitor and is a promising agent for repurposing to target FOXM1 and for the treatment of TNBC."

Acute Myelogenous Leukemia • Breast Cancer • Hematological Malignancies • HER2 Breast Cancer • HER2 Positive Breast Cancer • Leukemia • Oncology • Solid Tumor • Triple Negative Breast Cancer • FOXM1 • PGR

In silico design of novel multitarget small molecule inhibitor LCI139 for the treatment of PTEN-mutant endometrial carcinoma (AACR 2024) - "Triple PI3K-CDK4/6-CDK9 inhibitor, LCI139, is nanomolar potent against PTEN mutant EC cell lines and displays decreased toxicity compared with CDK9 inhibitor reference compounds, AZD4573 and flavopiridol. Our results merit further mechanistic dissection of PTEN interaction with PI3K pathway signaling, cell cycle machinery, CDK9-mediated transcriptional control. These data support extensive in vivo potency, toxicity, PK/PD studies to assess LCI139's clinical utility in treating EC."

Endometrial Cancer • Oncology • Solid Tumor • ANXA5 • CDK6 • MCL1 • PIK3CA • PIK3CD • PIK3CG • PTEN

Selective effects of cyclin dependent kinase inhibitors in gammaherpesvirus reactivation from latency. (PubMed, bioRxiv) - "However, all broad spectrum CDK inhibitors tested, Dinaciclib, Alvocidib, and Seliciclib, decreased both reactivation from latency and primary lytic replication. In contrast, the impact of targeted CDK 4/6 inhibitors, Palbociclib, Ribociclib, and Abemaciclib, was more nuanced, with decreased reactivation when given concurrently, but increased reactivation when administered prior to induction. These findings were consistent for both murine gammaherpesvirus and Epstein-Barr Virus. Overall, our data indicate that CDK inhibitors may be useful for targeted treatment of gammaherpesvirus-associated cancers, but optimal use of targeted CDK 4/6 inhibitors requires careful consideration of cell state and order of therapies."

Journal • Epstein-Barr Virus Infections • Hematological Malignancies • Infectious Disease • Kaposi Sarcoma • Lymphoma • Oncology • Sarcoma • Solid Tumor

Dual-Targeting Cuproptosis and Mitophagy via a Flavopiridol-Copper Nanoplatform Potentiates Immunotherapy Against Uveal Melanoma. (PubMed, Adv Sci (Weinh)) - "This work establishes cuproptosis induction via NP@Fla-Cu as a transformative strategy against UM, effectively addressing challenges in tumor selectivity and off-target toxicity. The dual functionality of flavopiridol as a copper ionophore and mitophagy activator provides a promising combinatorial approach to overcome therapy resistance in immunosuppressive malignancies."

IO biomarker • Journal • Tumor mutational burden • Eye Cancer • Immunology • Melanoma • Oncology • Solid Tumor • Uveal Melanoma • CD8 • TMB

Inhibition of CDK9 alleviates osteoarthritis by suppressing inflammation and reducing chondrocyte apoptosis. (PubMed, Front Pharmacol) - "CDK9 expression was modulated using siRNA, overexpression plasmids, and the inhibitor flavopiridol (FLA)...Our findings demonstrate that CDK9 plays a critical role in PTOA pathogenesis. Inhibition of CDK9 alleviates disease progression by suppressing the NF-κB signaling pathway, highlighting its potential as a therapeutic target for PTOA."

Journal • Immunology • Inflammation • Mood Disorders • Osteoarthritis • Pain • Rheumatology • CDK9 • IL1B • IL6 • TGFB1 • TNFA

Pharmacokinetics of intra-articular delivery of flavopiridol-loaded microparticles reveal sustained effects in Lewis rats. (PubMed, Am J Vet Res) - "In contrast, IA administration of microparticle encapsulated inhibitors offers sustained release and prolonged drug exposure at the target site while minimizing systemic side effects. The microparticle-based sustained-release formulation provides a promising means for the prevention and long-term treatment of joint inflammation and OA in both humans and animals."

Journal • PK/PD data • Preclinical • Immunology • Inflammation • Osteoarthritis • Pain • Rheumatology • CDK9

Unveiling the Therapeutic Potential of Flavones: A Review on Biological Activities and Mechanisms. (PubMed, Phytother Res) - "Some secondary metabolites, such as flavopiridol and riviciclib, have progressed to clinical trials as cyclin-dependent kinase (CDK) inhibitors. In this respect, we can consider flavones as a bioactive class of compounds with considerable potential for the development of new drugs. We expect more detailed mechanistic studies with SAR correlation to enable the production of new flavone compounds to broaden the use of these compounds to treat cancer, inflammation, and infectious diseases."

Journal • Review • Diabetes • Infectious Disease • Metabolic Disorders • Oncology

Use of Small-Molecule Inhibitors of CILK1 and AURKA as Cilia-Promoting Drugs to Decelerate Medulloblastoma Cell Replication. (PubMed, Biomedicines) - " The results demonstrated the potential of using cilia-promoting drugs, such as Alvocidib and Alisertib, to suppress cancer cell replication. Additionally, it shows the massive benefits of integrating accessible large language models to conduct sweeping, rapid, and accurate literature searches."

Journal • Brain Cancer • Medulloblastoma • Oncology • Solid Tumor • AURKA

Chromatin accessibility dynamics and transcriptional regulation in Tetrahymena thermophila. (PubMed, Sci China Life Sci) - "Moreover, transcriptional inhibition by flavopiridol reduces chromatin openness upstream of TSSs while enhancing nucleosome organization downstream of TSSs, underscoring the direct impact of transcription on shaping chromatin structure. Comparative analyses across 13 eukaryotic species further indicate that upstream-biased accessibility is an ancestral trait in unicellular eukaryotes, whereas higher vertebrates have evolved more complex promoter architectures. These findings not only establish T. thermophila as a powerful model for dissecting chromatin-dependent gene regulation but also provide novel insights into the evolutionary divergence of chromatin organization across the eukaryotic lineage."

Journal

Efficacy of novel agents in the treatment of acute myeloid leukemia and myelodysplastic syndrome: A systematic review and meta-analysis (ASH 2025) - "Newer agents included for AML were Guadectiabine, Magrolimab, Alvocidib, Enasidenib, Flotetuzumab, Vadastuximab, Mitoxantrone, Pevonedistat, Entospletinib, Eprenetapopt, Belinostat, Onvansertib, Panobinostat, Cediranib Maleate, Nilotinib, Emavusertib, and anti-CD45 antibody (DOTA-BC8). The newer agents investigated for MDS included Rigosertib, Imetelstat, Pembrolizumab, Enasidenib, Sabatolimab, Ivosidenib, Elitercept, Pevonedistat, Emavusertib, Atezolizumab, and Olutasidenib...All patients were treated concomitantly with either azacitidine (77%) or decitabine (23%)... This meta-analysis and systematic review demonstrate promising efficacy for novel agents in AML and MDS patients. There is a need for prospective trials with larger patient populations to investigate these agents further."

Retrospective data • Review • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Neutropenia • TP53

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

Clinical-data-driven pharmacological framework in liver disease: From liver cirrhosis to hepatocellular carcinoma. (PubMed, Br J Pharmacol) - "The CH-CCNB1 complex exhibited high stability, indicating that CH may represent potential candidate warranting further study against LC, HCC and ANT."

Clinical data • Journal • Fibrosis • Gastroenterology • Hepatocellular Cancer • Hepatology • Immunology • Liver Cirrhosis • Oncology • Solid Tumor • CCNB1

Discovering bioactive pharmaceuticals from natural products for type 2 diabetes mellitus using network pharmacology, molecular docking, and molecular dynamics. (PubMed, Sci Rep) - "72 natural compounds exhibited superior or comparable binding affinities to standard drugs of which, 17 ligands -Moracin D, Moracin P, Plantagineoside A, Pyrene (carcinogenic), Curcumin, Rohitukine, Berberine Chloride, Berberrubine, Apigenin, Emodin, Chelerythrine, Alvocidib, A-443,654, Xambioona, Altertoxin I, Ursolic Acid, and Oleanolic Acid -were selected as top candidates for further analysis. ADME/T analyses highlighted Pyrene, Guggulsterone, Melatonin, Gefitinib, Apigenin, Rotenone, Curcumin, Bavachinin A, Bavachinin, and Quinidine as particularly promising in terms of superior ADME and oral bioavailability...This study highlights the effectiveness of in-silico techniques to identify natural products as prospective alternative or adjunct therapies for T2DM. Further experimental validation is necessary to confirm compounds' efficacy and safety, paving the way for future clinical investigations."

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus • AKT2 • AMPK • IR • MAPK8 • PPARG • PTPN1 • SLC2A4

From Scarcity to Survival: Adaptive Strategies of A549 Lung Cancer Cells Under Serum Starvation. (PubMed, Thorac Res Pract) - "Serum deprivation triggers complex adaptive responses in A549 cells, influencing morphology, migration, stemness, drug sensitivity, and gene expression. Low-serum conditions promoted stress-adaptive and survival phenotypes relevant for modeling tumor microenvironments. These findings suggest that serum availability is a crucial determinant of cancer cell plasticity and behavior. Moreover, long-term adaptation to serum limitation may mimic the nutrient-restricted conditions of solid tumors, providing a valuable in vitro model for studying metabolic flexibility and therapy resistance mechanisms in lung cancer cells."

Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD133

Exploring the Mechanisms of Venetoclax Resistance Via Drug Screening and Genome-Wide CRISPR Screening (ASH 2023) - "Among these hits, CDK2 correlates with our drug screening data indicating Flavopiridol as an effective compound in treating VeR cell lines. Integrating a range of screening approaches may lead to discovering previously unknown therapeutic targets for venetoclax-resistant AML. Our screens confirmed previously described involvement of the apoptotic pathway genes in venetoclax resistance as well as identified some novel promising targets. Our ongoing efforts involve thorough validations of the identified hits from CRISPR and drug screening to enhance the reliability and translatability of the results."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CDK2 • ELAVL1 • TP53

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 • CD34 • CDK2 • CDK4 • CEBPA • ELANE • SRP54

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