CUDC-101 / Curis - LARVOL DELTA

Developing epigenetic synergistic drug combinations with albendazole in paediatric acute myeloid leukaemia (ASH 2025) - "Similar anthelmintic agents, mebendazole (MBZ) and parbendazole (PBZ), have been reported to have effects on epigenetic regulators that alter C-MYB degradation (Walf-Vorderwülbecke et al...These epigenetic hits represent various target families such as HDAC inhibitors (vorinostat, panobinostat, and CUDC-101), BET inhibitors (OTX-015, PFI-1, and (-)-JQ), aurora kinase inhibitors (MK-8745 and JNJ-7706621), and DNA synthesis inhibitors (cytarabine)...HDAC inhibitors (vorinostat), BET inhibitors (OTX-015) and histone methyltransferase (MS023) were among the most represented epigenetic target families, indicating potential mechanism of action of the novel ABZ+epigenetic combination. The novel drug candidate ABZ was found to have remarkable anti-leukaemia efficacy in murine and human models of childhood AML in vitro and in vivo while having negligible effects in normal cells. Current work is focused on evaluating ABZ+epigenetic synergistic combinations that will be taken..."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Pediatrics • HOXA9 • IL1B • MEIS1

IR783-Stabilized Nanodrugs Enhance Anticancer Immune Response by Synergizing Oxidation Therapy and Epigenetic Modulation. (PubMed, Adv Sci (Weinh)) - "In this study, it is found that incorporating β-lapachone-based oxidation therapy with CUDC101-initiated epigenetic regulation results in synergistic antitumor effects and potent immune activation...Besides, nanodrugs can inhibit both primary and distant tumor growth effectively by elevating systemic anticancer immunity. This study provides a promising approach to synergize oxidation therapy with epigenetic modulation for safe and efficient breast cancer immunotherapy."

IO biomarker • Journal • Breast Cancer • Gene Therapies • Oncology • Solid Tumor • Triple Negative Breast Cancer

NAT2 activity increases cytotoxicity of anthracycline antibiotics and HDAC inhibitors. (PubMed, Biochim Biophys Acta Mol Basis Dis) - "Among those 147 drugs we found doxorubicin, daunorubicin, epirubicin, valrubicin, teniposide, afatinib, carmustine, vincristine, panobinostat, and vorinostat to have increased toxicity to cancer cells expressing the rapid NAT2 allele. Additionally, we report NAT2-mediated acetylation of idarubicin, daunorubicin, doxorubicin, vorinostat, and CUDC-101. These findings have implications for pharmacogenomics and cancer precision medicine using conventional chemotherapeutic drugs, as improving their efficacy and safety may affect >4 million cancer patients worldwide that receive these drugs as standard of care."

Journal • Oncology • NAT2

A high-throughput, microplate reader-based method to monitor in vitro HIV latency reversal in the absence of flow cytometry. (PubMed, Virology) - "We show that HIV reactivation by control LRAs like prostratin and romidepsin is readily detected with dose dependence and with significant correlation and sensitivity to standard flow cytometry. Using this method, we screen 79 epigenetic modifiers and identify CUDC-101, molibresib, and quisinostat as novel LRAs. This microplate reader-based method offers accessibility to researchers in resource-limited regions to work with J-Lat cells and more actively participate in global HIV cure research efforts."

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

HDAC Inhibitors Can Enhance Radiosensitivity of Head and Neck Cancer Cells Through Suppressing DNA Repair. (PubMed, Cancers (Basel)) - " We identified that histone deacetylases (HDACs) were prominent candidates, and subsequently identified that the HDAC inhibitors mocetinostat and pracinostat, as well as the combined HDAC-epidermal growth factor receptor inhibitor CUDC-101, were effective at radiosensitising cell models of HNSCC (FaDu, A253, UMSCC11b) through their impact on both spheroid growth and clonogenic survival assays. We also demonstrated that this combinatorial strategy leads to inhibition of the repair of DNA double-strand breaks through the neutral comet assay and γH2AX foci analysis using immunofluorescence microscopy, providing a mechanism of action through which HDAC inhibition functions in HNSCC radiosensitisation. We believe that this approach should be further investigated in preclinical models, in order to realise the full therapeutic potential of HDAC inhibition for the radiosensitisation of HNSCC, eventually leading to improved patient treatment efficacy and outcomes."

Journal • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • EGFR

Epigenetic Drug Profiling for Breast Cancer Therapy: A Focus on Receptor Modulation and Heterogeneity (SABCS 2024) - "Interestingly, (+)-JQ1(BET bromodomain inhibitor), I-BRD9 (BRD9 inhibitor) and CUDC-101 (HDAC inhibitor) drastically reduced Ki67 level. Overall, these findings suggest a potential for combination therapy. While further investigation of these promising candidates is needed (3D, ex vivo, and in vivo testing), this investigation reveals new possibilities to overcome therapeutic resistance in breast cancer."

Heterogeneity • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER • EZH2 • HER-2 • PARP1 • PGR • SOX9

Regulation of reactive oxygen molecules in pakchoi by histone acetylation modifications under Cd stress. (PubMed, PLoS One) - "In this work, we investigated this issue using Cd-stressed pakchoi seedlings treated with six epi-modification inhibitors (5-AC, RG108, TSA, CUDC101, AT13148, and H89) as experimental materials. Also, TSA addition at high concentrations could also increase Cd-induced ROS accumulation. Based on this, we propose that the ROS molecular pathway may be related to epigenetic regulation, and chromatin modification may affect ROS accumulation by regulating gene expression, providing a new perspective for studying the regulatory mechanism of epigenetic modification under abiotic stress."

Epigenetic controller • Journal

Multi-Target Inhibitor CUDC-101 Impairs DNA Damage Repair and Enhances Radiation Response in Triple-Negative Breast Cell Line. (PubMed, Pharmaceuticals (Basel)) - "CUDC-101 effectively enhances response to both proton and X-ray irradiation, in the triple-negative MDA-MB-231 cell line. This enhancement was most notable when CUDC-101 was combined with proton irradiation. This study highlights that CUDC-101 holds potential in the management of triple-negative breast cancer as monotherapy or in combination with protons or X-ray irradiation."

Journal • Preclinical • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2

Cytotoxicity and inhibitory potential of CUDC-101 in non-small cell lung cancer cells with rare EGFR L861Q mutation. (PubMed, Curr Res Toxicol) - "In this study, the four cell lines containing the L861Q mutation were constructed by CRISPR and the anti-tumour effects of CUDC-101 on them were investigated in vitro by various chemosensitivity methods, with afatinib serving as a positive control. The results demonstrated that CUDC-101 inhibited the proliferation and clonogenic capacity on the four cells through the ERK or AKT pathways, decreased the mitochondrial membrane potential of the cells, blocked the cell cycle and promoted apoptosis. Our findings suggest that CUDC-101 may be a promising treatment option for NSCLC patients with the EGFR exon 18 substitution mutation L861Q."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

A high-throughput, microplate reader-based method to monitor in vitro HIV latency reversal in the absence of flow cytometry. (PubMed, bioRxiv) - "We show that HIV reactivation by control LRAs like prostratin and romidepsin is readily detected with dose dependence and with significant correlation and sensitivity to standard flow cytometry...Using this method, we screen 79 epigenetic modifiers and identify molibresib, quisinostat, and CUDC-101 as novel LRAs. This microplate reader-based method offers accessibility to researchers in resource-limited regions to work with J-Lat cells and more actively participate in global HIV cure research efforts. J-Lat T-cell lines are important to HIV cure research but require flow cytometryWe describe a method to work with J-Lat cells using a standard microplate readerThis assay can detect control LRAs similar to flow cytometry and discover new LRAsThis assay allows low-resourced laboratories to contribute to HIV cure research."

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

Synergistic effect of docetaxel combined with a novel multi-target inhibitor CUDC-101 on inhibiting human prostate cancer. (PubMed, Pathol Res Pract) - "To conclude, these results demonstrated that the combination of CUDC-101 with DTX had a synergistic and significantly improved anti-carcinogenic effect. This combination may serve as a potential strategy for clinical treatment and prognosis improvement in PCa."

Journal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CDH1 • MMP9 • VIM

CUDC‑101 is a potential target inhibitor for the EGFR‑overexpression bladder cancer cells. (PubMed, Int J Oncol) - "These results supported the proposed cytotoxic effects of CUDC‑101, in addition to its inhibitory effects on cell division and proliferation in EGFR‑overexpressing bladder cancer cells. Therefore CUDC‑101 may to be a potential therapeutic option for the treatment of bladder cancer."

Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urethral Cancer • Urology • EGFR

Non-oncology drug (meticrane) shows anti-cancer ability in synergy with epigenetic inhibitors and appears to be involved passively in targeting cancer cells. (PubMed, Front Oncol) - "2) Meticrane showed additive/synergistic effects with epigenetic inhibitors (DNMT1/5AC, HDACs/CUDC-101 and HDAC6/ACY1215). Beyond that, we have expressed some concerns confronted during testing meticrane that also apply to other non-oncology drugs when considered for future clinical or preclinical purposes. Taken together, meticrane is involved in some anticancer pathways that are passively targeting cancer cells and may be considered as compatible with epigenetic inhibitors."

IO biomarker • Journal • Cardiovascular • Gastrointestinal Cancer • Hematological Disorders • Hematological Malignancies • Hepatology • Hypertension • Leukemia • Liver Cancer • Multiple Myeloma • Oncology • Solid Tumor • DNMT1 • HAVCR2 • PD-L1

CUDC-101 as a dual-target inhibitor of EGFR and HDAC enhances the anti-myeloma effects of bortezomib by regulating G2/M cell cycle arrest. (PubMed, J Zhejiang Univ Sci B) - "The results showed that this drug combination had a synergistic anti-myeloma effect by inducing G2/M phase blockade. Collectively, our findings revealed that CUDC-101 could act on its own or in conjunction with bortezomib, which provides insights into exploring new strategies for MM treatment."

Journal • Acute Promyelocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • EGFR • HER-2

Visualized TEMPO-based polymers for hepatocellular carcinoma therapy (ACS-Sp 2023) - "Based on the aberrant glucose metabolism and immune evasion in hepatocellular carcinoma (HCC), a novel material system consisting of a glucose and TEMPO at the distal ends of PEO-b-PLLA block copolymer (glucose-PEO-b-PLLA-TEMPO), is designed to encapsulate clinical therapeutics CUDC101 and photosensitizer IR780, showing the outstanding multimodal imaging and enhanced drug delivery in vivo...And its integrity in the artery for a desired period of time, making it a reservoir for the sustained release of chemotherapeutic drugs in HCC therapy. In conclusion, the design of a visualized TEMPO-based polymer system is of great value for its future clinical application in HCC."

Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

EGFR and HDAC Dual-Target Inhibitor CUDC-101 Enhances the Anti-Myeloma Effects of Bortezomib By Regulating the G2/M Cell Cycle Arrest (ASH 2022) - "In addition, CUDC-101 has been reported to exert a synergistic effect with a lot of conventional drugs, for example, Gemcitabine, Arsenic trioxide, or Carfilzomib. Further investigation revealed that the G2/M phase arrest is a pivotal mechanism to achieve this effect, which involves the upregulation of P21 and P27. And these data prove that CUDC-101 is an effective agent in MM therapy.Conclusion In summary, we have confirmed the efficacy of CUDC-101 in MM treatment as a single drug or in combination with Bortezomib, and our findings offer a new strategy for MM therapy."

Hematological Disorders • Hematological Malignancies • Immune Modulation • Inflammation • Multiple Myeloma • Oncology • CDKN1A • EGFR • HER-2 • SDC1

Patient-derived organoids for personalized gallbladder cancer modelling and drug screening. (PubMed, Clin Transl Med) - "Patient-derived organoids are potentially a useful platform to explore molecular pathogenesis of gallbladder tumours and discover personalized drugs."

Journal • Preclinical • Gallbladder Cancer • Gastroenterology • Gastrointestinal Cancer • Gastrointestinal Disorder • Hepatology • Oncology • Solid Tumor

Dual Tumor Microenvironment Remodeling by Glucose-Contained Radical Copolymer for MRI Guided Photo-Immunotherapy. (PubMed, Adv Mater) - "Herein, a novel material system consisting of a glucose and TEMPO (2,2,6,6-tetramethylpiperidin-1-yl)oxyl) at the distal ends of PEO-b-PLLA block copolymer (Glucose-PEO-b-PLLA-TEMPO), was designed to encapsulate clinical therapeutics CUDC101 and photosensitizer IR780...Efficient delivery of CUDC101 and IR780 was achieved to synergize the antitumor immune activation through IR780-mediated photodynamic therapy (PDT) and CUDC101 triggered CD47 inhibition, showing M1 phenotype polarization of tumor-associated macrophages (TAMs). More intriguingly, this study demonstrates PDT-stimulated p53 can also re-educate TAMs, providing a combined strategy of using dual tumor microenvironment remodeling to achieve the synergistic effect in the transition from cold immunosuppressive to hot immunoresponsive tumor microenvironment."

Biomarker • Journal • Tumor microenvironment • Oncology • MRI

An organoid-based screen for epigenetic inhibitors that stimulate antigen presentation and potentiate T-cell-mediated cytotoxicity. (PubMed, Nat Biomed Eng) - "We show that the epigenetic inhibitors GSK-LSD1, CUDC-101 and BML-210, identified by the screen, display antitumour activities in orthotopic mammary tumours in mice, that they upregulate antigen presentation mediated by the major histocompatibility complex class I on breast tumour cells and that treatment with BML-210 substantially sensitized breast tumours to the inhibitor of the checkpoint programmed death-1. Standardized measurements of tumour-cell killing activity facilitated by tumour-organoid-T-cell screens may help with the identification of candidate immunotherapeutics for a range of cancers."

Journal • Breast Cancer • Immune Modulation • Inflammation • Oncology • Solid Tumor

Discovery of Inhibitors for Mycobacterium Tuberculosis Peptide Deformylase Based on Virtual Screening in Silico. (PubMed, Mol Inform) - "These compounds showed IC values from 0.5 μmol/L to 112 μmol/L against MtPDF, among which CUDC-101 bearing hydroxamic acid exhibited IC of 0.5 μmol/L on MtPDF and MIC against Mycobacterium smegmatis of 32 μg/mL, and Ixazomib Citrate with IC of 63 μmol/L and MIC of 16 μg/mL. CUDC-101 and Ixazomib Citrate are promising as the potential leads for antituberculotics."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

CUDC-101 enhances the chemosensitivity of gemcitabine-treated lymphoma cells. (PubMed, Leuk Res) - "Together, our results highlight the anti-cancer properties of CUDC-101 alone or in combination with gemcitabine as an approach to inducing the apoptotic death of lymphoma cells in vitro, while also offering insight into the underlying molecular mechanisms governing this activity."

Journal • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Synergistic efficacy of combined EGFR and HDAC inhibitors overcomes tolerance to EGFR monotherapy in salivary mucoepidermoid carcinoma. (PubMed, Oral Oncol) - "MEC cells are intrinsically tolerant to EGFR inhibition. Combining EGFR and HDAC inhibitors exerts synergistic and potent cytotoxic effects, suggesting that EGFR inhibitors still hold significant promise against MEC. Future studies are needed to assess the applicability and efficacy of dual EGFR-HDAC inhibitors for the clinical management of MEC."

Clinical • Journal • Monotherapy • Head and Neck Cancer • Oncology • Salivary Gland Cancer • Solid Tumor • Squamous Cell Carcinoma • EGFR

Comprehensive review for anticancer hybridized multitargeting HDAC inhibitors. (PubMed, Eur J Med Chem) - "Notably, and during this short period, there are four HDAC inhibitor hybrids have entered different phases of clinical trials for treatment of different types of blood and solid tumors, namely; CUDC-101, CUDC-907, Tinostamustine, and Domatinostat. The designed multitarget hybrids include topoisomerase inhibitors, kinase inhibitors, nitric oxide releasers, antiandrogens, FLT3 and JAC-2 inhibitors, PDE5-inhibitors, NAMPT-inhibitors, Protease inhibitors, BRD4-inhibitors and other targets. This review may help researchers in development and discovery of new horizons in cancer treatment."

Journal • Review • Developmental Disorders • Oncology • Solid Tumor • NAMPT

Curis to present at the 10th Annual Needham Healthcare Conference (Bradenton Herald) -

An overview of Curis’ proprietary drug candidates, including CUDC-101, & CUDC-907, an HDAC/PI3 kinase inhibitor, will be presented at the Needham 10th Annual Healthcare Conference at 11:20 a.m. EDT on April 5, 2011, in New York City;

Oncology

CUDC-101, a hybrid molecular targeted agent, reverses multiple mechanisms of drug resistance (AACR 2013) - Abstract#: 976; Presentation Time: Sunday, Apr 07, 2013, 1:00 PM - 5:00 PM; " In Pt-resistant cancer cells, CUDC-101 appears to circumvent the resistance through inhibition of both MRP-2 and other DNA repair-mediated mechanisms. The combinations of CUDC-101 with cisplatin or oxaliplatin were found to display synergistic cytotoxic effect in cisplatin- or oxaliplatin-resistant cancer cell lines, respectively."

Preclinical • Oncology