fimepinostat (CUDC-907) / Curis - LARVOL DELTA

CUDC-907 attenuates pulmonary fibrosis by reversing HDAC1-mediated SMAD4 deacetylation at lysine 45. (PubMed, Biol Direct) - "Furthermore, therapeutic administration of CUDC-907 significantly ameliorates lung injury and collagen deposition in a bleomycin-induced mouse model. Collectively, our findings identify SMAD4 K45 acetylation as a critical molecular switch in fibrogenesis and position CUDC-907 as a promising epigenetic strategy for the treatment of fibrotic lung diseases."

Journal • Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • HDAC1 • SMAD4 • TGFB1

Selection of effective LRAs using a newly designed in vitro HIV latency reactivation protocol: toward future application in HIV samples. (PubMed, Microbiol Spectr) - "Using this method, we identified PEP005 and CUDC-907 as the most potent LRAs across multiple experimental settings. We developed a simple and reproducible assay to identify compounds capable of reactivating latent virus, a key step in cure strategies. Using this approach, we identified effective latency-reversing compounds and, through collaboration with Dompé using the EXSCALATE platform, we also identified Tandutinib as a promising new candidate for further investigation."

Journal • Preclinical • Human Immunodeficiency Virus • Infectious Disease • Pediatrics • CD4

Dual HDAC/PI3K inhibitors as a potential and emerging cancer therapy: a review. (PubMed, Future Med Chem) - "Dual inhibitors, such as CUDC-907 and BEBT-908, and their potential effectiveness in cytogenetic cancers and solid tumors; issues related to clinical trials; and future directions to enhance therapeutic outcomes are discussed. Currently, dual HDAC/PI3K inhibitors are an exciting next-generation anticancer agent that addresses the major drawbacks of existing therapies."

Journal • Review • Oncology • Solid Tumor

CUDC-907 inhibits glioblastoma and enhances glioblastoma sensitivity to temozolomide by inhibiting DNA damage repair. (PubMed, Genes Dis) - "RNA sequencing suggests that CUDC-907 achieves its effects by influencing the glioblastoma cell cycle and inhibiting DNA damage repair. Overall, the data suggest that CUDC-907 may be a promising anti-cancer agent for glioblastoma treatment."

Journal • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

Ex Vivo Characterization Studies Identify Candidate Therapies for the Individualized Care of NF2-Related Schwannomatosis. (PubMed, Cancers (Basel)) - "Drug sensitivity screens in 2- and 3-dimensional formats revealed cytotoxic effects of fimepinostat in primary cells; dasatinib with brigatinib was the most effective cytostatic combination. Ineffective therapies attempted in the patient were also ineffective ex vivo. These data support the idea of using the FPM workflow to improve and individualize the standard of care for severe NF2-SWN patients using surgical samples."

Journal • Preclinical • Brain Cancer • Oncology • Pediatrics • Solid Tumor

Large-scale drug screening identifies clinically actionable combinations to overcome BTK/PI3K inhibitor resistance in marginal zone lymphoma (AACR 2026) - "Here, we present data from a large pharmacological screen involving over 3,500 compounds in 2 MZL models with secondary resistance to BTK/PI3Ki, developed through prolonged exposure to idelalisib (Arribas 2022) or ibrutinib (Arribas 2025).Methods...Adding the alisertib (AURKAi), rigosertib (PLKi), fimepinostat (PI3K/HDACi), lanatoside-C (Na+K+ATPase), astragalin (apoptosis), astragaloside-I (WNT) and oridonin (AKT) was of benefit (additivity or synergism) in both parental and resistant cells.Conclusions...Several clinically advanced agents—particularly PAK4/NAMPT, AURKA, WNT, and Na⁺/K⁺-ATPase inhibitors—enhanced or restored the activity of BTKi/PI3Ki. These findings highlight new therapeutic strategies for relapsed/refractory MZL and support clinical evaluation of targeted combinations to overcome acquired resistance."

Clinical • Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Oncology • AURKA • NAMPT

Patient-derived model systems of endometrial cancers for disease modeling and drug sensitivity testing (AACR 2024) - "The drug screening results clearly highlighted several standout drugs, including CUDC-907 (a dual PI3K/HDAC inhibitor), two histone deacetylase (HDAC) inhibitors including romidepsin and panobinostat, four topoisomerase II (TOP II) inhibitors including mitoxantrone, daunorubicin, doxorubicin, and epirubicin, two proteasome inhibitors including carfilzomib and bortezomib, 2 DNA-directed RNA synthesis inhibitor dactinomycin and plicamycin, omacetaxine mepesuccinate (protein synthesis inhibitor), and valrubicin (DNA synthesis inhibitor). Our unique PDXs and PDCs are excellent models for representing various characteristics of EC and testing novel therapeutics. This current study presents a promising direction for developing personalized therapy options for EC patients and provides a platform for further investigation of drug mechanisms and tumor development. Future studies will also involve etiology, such as chronic psychological stress, DNAm age and intratumoral microbiome."

Clinical • Endometrial Cancer • Gynecologic Cancers • Oncology • Solid Tumor

Identifying the molecular mechanisms underlying progesterone receptor downregulation in endometrial cancer (AACR 2024) - "Single treatment with mitoxantrone, idarubicin, romidepsin , CUDC-907 , FLZ , and RocA achieved effective inhibition of EC cell proliferation and enhanced PR expression except FLZ and RocA. Co-treatment of CUDC-907 with Top2Ai increased PR expression and enhanced cell death in EC cell lines, indicating a potential treatment strategy. In vivo studies utilizing our EC-PDX models will further validate the efficacy of restoring PR expression and suppressing EC tumor growth. Further studies of the molecular mechanisms behind this strategy will be conducted."

Cervical Cancer • Endometrial Cancer • Gynecologic Cancers • Oncology • Solid Tumor • HDAC2 • PGR • TOP1 • TOP2A

Increasing the therapeutic vulnerability of heterogenous cell phenotypes within prostate cancer (AACR 2024) - "Tested compounds with differential sensitivity between aggressive and non-aggressive cells were those inhibiting histone deacetylase (vorinostat, fimepinostat, and pracinostat), proteasomes (bortezomib, delanzomib, ixazomib), topoisomerases (gimatecan and daunorubicin), and other compounds identified independently by us targeting nicotinamide phosphoribosyl transferase (FK866) and DNA (bleomycin). Funding was provided by the University of Arizona Cancer Center (NCI-P30 CA23074 and NCI-R01 CA159406) and by the Partnership in Native American Cancer Prevention at the University of Arizona (U54CA143924) and Northern Arizona University (U54CA143925). Collaborators at NCATS were supported by the intramural research program."

Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor • CDH1 • CLDN4 • CLDN7 • KRT6A • ZEB1

Fimepinostat Promotes Apoptosis and Decreases Cytokine Secretion in NF2-Related Human Schwannoma Cells. (PubMed, Int J Mol Sci) - "Moreover, fimepinostat downregulated cytokine and chemokine secretion increased by merlin loss in schwannoma cells. Fimepinostat is a promising new drug intervention for NF2-SWN patients with the potential to promote tumor regression."

Journal • Brain Cancer • Genetic Disorders • Neurofibromatosis • Oncology • Solid Tumor • CASP3 • CDKN1A • TNFRSF1A

Trametinib and Fimepinostat Induce Malignant Peripheral Nerve Sheath Tumor Cell Death In Vitro. (PubMed, Cancers (Basel)) - "These studies demonstrate in vitro efficacy for two candidate MPNST therapeutics which could reduce tumor burden and metastasis in NF1 patients."

Journal • Preclinical • Brain Cancer • Genetic Disorders • Melanoma • Neurofibromatosis • Neurofibrosarcoma • Oncology • Sarcoma • Solid Tumor • NF1

Trial of CUDC-907 in Children and Young Adults With Relapsed or Refractory Solid Tumors, CNS Tumors, or Lymphoma (clinicaltrials.gov) - P1 | N=26 | Completed | Sponsor: Dana-Farber Cancer Institute | Active, not recruiting ➔ Completed

Trial completion • B Cell Lymphoma • Brain Cancer • CNS Tumor • Glioma • Hematological Malignancies • Lymphoma • Neuroblastoma • Oncology • Solid Tumor • MYC • MYCN

Phosphatidylinositol-3-Kinase (PI3K) and Histone Deacetylase (HDAC) Multitarget Inhibitors: An Update on Clinical and Preclinical Candidates. (PubMed, Pharmaceuticals (Basel)) - "This review examines the rational design and synthetic evolution of dual PI3K/HDAC inhibitors, an area catalyzed by the development of fimepinostat, the first clinically evaluated agent exhibiting potent and balanced inhibition of both targets...From this comprehensive analysis, we outline key considerations and emerging design principles that may inform the next generation of PI3K/HDAC multitarget drug candidates. Insights derived from the diversity of chemical scaffolds, activity profiles, and selectivity patterns described herein may support the development of innovative therapeutic agents capable of overcoming current limitations in anticancer treatment."

Journal • Preclinical • Review • Oncology

A Phase 1 Trial of Fimepinostat in Children and Adolescents With Relapsed and Refractory Solid and CNS Tumors. (PubMed, Cancer Med) - P1 | "Fimepinostat was tolerable at a dose of 35 mg/m2 in children with relapsed and refractory solid and CNS tumors, but lacked significant clinical activity. Discovery of drugs to target Myc continues to be a high priority for childhood cancers."

Journal • P1 data • B Cell Lymphoma • Brain Cancer • Burkitt Lymphoma • CNS Tumor • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Lymphoma • Neuroblastoma • Non-Hodgkin’s Lymphoma • Oncology • Pediatrics • Solid Tumor • MYCN

Dual PI3K and HDAC inhibitor, CUDC-907, effectively inhibits endometrial cancer growth in vitro and in vivo. (PubMed, Front Oncol) - "Our findings suggest that CUDC-907 is a promising agent that can re-sensitize tumors to progestin therapy and improve outcomes for EC patients. This study supports CUDC-907 as a potent treatment strategy in endometrial cancer and identifies IGF-1 as a potential surrogate serum biomarker for therapeutic response."

Journal • Preclinical • Endometrial Cancer • Genetic Disorders • Obesity • Oncology • Solid Tumor • CDKN1A • EIF4EBP1 • HER-2 • IGF1 • PGR

Trial of CUDC-907 in Children and Young Adults With Relapsed or Refractory Solid Tumors, CNS Tumors, or Lymphoma (clinicaltrials.gov) - P1 | N=26 | Active, not recruiting | Sponsor: Dana-Farber Cancer Institute | Trial completion date: Oct 2025 ➔ Feb 2026 | Trial primary completion date: Oct 2025 ➔ Jan 2026

Trial completion date • Trial primary completion date • B Cell Lymphoma • Brain Cancer • CNS Tumor • Glioma • Hematological Malignancies • Lymphoma • Neuroblastoma • Oncology • Solid Tumor • MYC • MYCN

Identifying Novel Epigenetic Therapies for T-Cell Lymphomas By High Throughput Drug Screen (ASH 2024) - "Introduction : Epigenetic alterations are known to contribute to development of T-cell lymphomas (TCL), and numerous epigenetic modifiers have shown safety and clinical efficacy in TCL leading to FDA approval of three histone deacetylase inhibiters (vorinostat, romidepsin, and belinostat)...At the conclusion of this screen, we tested cytotoxicity of our most encouraging compound in combination with other top performing compounds.Results : We identified BI-847325, bortezomib, camptothecin, CUDC-907, and WAY-118959-A as the most encouraging cytotoxic compounds that are not currently being used clinically. We compared the top 5 compounds to 4 standard of care (SOC) cytotoxic drugs (belinostat, gemcitabine, romidepsin, and vincristine) that are used clinically...We tested cytotoxicity of camptothecin in combination with 5 compounds (belinostat, bortezomib, BI-847325, romidepsin, and vincristine) that also demonstrated cytotoxicity in the malignant T-cells with relative..."

Cutaneous T-cell Lymphoma • Gene Therapies • Hematological Malignancies • Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma • ANXA5

Dual HDAC and PI3K Inhibitor CUDC-907 Inhibits Growth of Pleural Mesothelioma: The Impact of Cisplatin Sensitivity and Myc Expression. (PubMed, Cells) - "Combining CUDC-907 with cisplatin further decreased cell growth even in cisplatin-resistant cells. The majority of PM cell models are sensitive to CUDC-907, which may be a potent therapeutic agent in PM."

Journal • Malignant Pleural Mesothelioma • Mesothelioma • Oncology • Pleural Mesothelioma • Solid Tumor • BAP1 • MYC • PTEN

CUDC-907 inhibits osteosarcoma through upregulation of PTX3 and inhibition of PI3K-AKT signaling. (PubMed, Eur J Pharmacol) - "This study further demonstrated that CUDC-907 related endogenous upregulation of PTX3 promotes apoptosis of osteosarcoma cells by inhibiting the PI3K-AKT pathway, which in turn elucidated the potential mechanism of osteosarcoma inhibition by CUDC-907. In conclusion, CUDC-907 promote apoptosis in osteosarcoma cells by promoting PTX3 expression and thus inhibiting the PI3K-AKT pathway."

Journal • Neuroblastoma • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • PTX3

Establishing a screening platform on patient-derived organoids to identify effective agents to treat glioblastoma (EANO 2025) - "Crizotinib (pintertumoral = 0.0002, pintratumoral = 0.0255), Fimepinostat (pintertumoral < 0.0001, pintratumoral = 0.0006) and Sunitinib (pintertumoral < 0.0001, pintratumoral = 0.0092) resulted in significant inter- as well as intratumoral differences in response to treatment. Nilotinib (pintertumoral = 0.0009), Dasatinib (pintertumoral = 0.0046), Sorafenib (pintertumoral = 0.0096) and Rapamycin (pintertumoral < 0.0001) showed intertumoral heterogeneity only. Last but not least, Selumetinib (pintratumoral = 0.0001) triggered significant intratumoral differences... Our findings support the use of PDOs as a promising ex vivo platform to model inter- and intratumoral heterogeneity and assess drug response in GBM. This study serves as a proof of concept for integrating drug panel testing into PDO-based workflows, highlighting its potential value for molecular tumor board decision-making. The observed variability in treatment response across tumor regions and..."

Clinical • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

CUDC-907 exerts an inhibitory effect on non-small cell lung cancer associated with induction of mitotic catastrophe and downregulation of YAP/TAZ signaling. (PubMed, Chem Biol Interact) - "Additionally, CUDC-907 treatment significantly inhibited tumor growth and reduced tumor weight in the tumor xenograft mouse model. Taken together, this study revealed the cytotoxic effects of CUDC-907 and its underlying mechanism, which suggests that CUDC-907 may be an effective therapeutic approach for treating NSCLC."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CASP3 • CASP8 • CASP9 • CCNA2 • CCNB1 • CDC25C • CDK1 • CDKN1A • ERN1 • GNRP • MAPK8 • PARP1 • PLK1

Fimepinostat is a dual inhibitor of tumor and angiogenesis in glioblastoma and synergizes with temozolomide through suppressing MYC. (PubMed, Korean J Physiol Pharmacol) - "Mechanism studies confirmed that fimepinostat acts on glioblastoma cells through suppressing Akt/MYC. Our findings suggest that dual targeting of tumor and angiogenesis by fimepinostat may provide an alternative approach for anti-glioblastoma therapy."

Journal • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

Molecular mechanisms of unique therapeutic potential of CUDC-907 for MEF2D fusion-driven BCP-ALL. (PubMed, Signal Transduct Target Ther) - "Furthermore, this compound's effectiveness and safety were confirmed in both MH/NRASG12D BCP-ALL mouse model and MB patient-derived xenograft (PDX) model, outperforming conventional therapies. These results support the therapeutic potential of dual-pathway inhibition in MEF2D fusion (+) BCP-ALL and suggest CUDC-907 as a promising candidate for precision treatment in fusion-driven leukemias with similar molecular dependencies."

IO biomarker • Journal • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • BCL2 • BCL9 • HDAC9 • HNRNPUL1 • MEF2D

Histone deacetylase inhibitors target DNA replication regulators and replication stress in Ewing sarcoma cells. (PubMed, Cancer Res Commun) - "In this study, we identified that multiple HDAC inhibitors, including fimepinostat, romidepsin and panobinostat, downregulate the levels of the RRM1, RRM2, CHK1, and WEE1 proteins in Ewing sarcoma cells, and impair DNA replication. Additionally, proteomic studies identified that HDAC inhibitors also downregulate the level of the BRD4 protein, a BET bromodomain protein that regulates both the transcriptional program of the EWS::FLI1 oncoprotein and DNA replication. Overall, these results provide novel insight into the molecular mechanisms by which HDAC inhibitors target cancer cells, regulate DNA replication, and inhibit the cellular response to DNA replication stress."

Journal • Ewing Sarcoma • Oncology • Sarcoma • Solid Tumor • BRD4 • CDT1 • CHEK1 • EWSR1 • FLI1 • MCM2 • RRM1 • RRM2

Fimepinostat, Combination HDAC and Pi3-kinase Inhibitor Tumor-Directed Therapy for Cushing Disease (clinicaltrials.gov) - P2 | N=20 | Recruiting | Sponsor: University of California, Los Angeles | Not yet recruiting ➔ Recruiting | Trial completion date: Jan 2025 ➔ Jan 2029 | Trial primary completion date: Jan 2025 ➔ Jan 2029

Enrollment open • Trial completion date • Trial primary completion date • Cushing’s Disease