- |||||||||| citarinostat (ACY-241) / BMS, Opdivo (nivolumab) / BMS
Phase classification, Trial completion date, Trial primary completion date, Combination therapy: Selective HDAC6 Inhibitor ACY 241 in Combination With Nivolumab in Patients With Unresectable Non Small Cell Lung Cancer (clinicaltrials.gov) - Jan 4, 2024
P1, N=16, Active, not recruiting,
Active, not recruiting --> Terminated; Lack of efficacy Phase classification: P1b --> P1 | Trial completion date: Jun 2023 --> Jan 2024 | Trial primary completion date: Jun 2023 --> Jan 2024
- |||||||||| citarinostat (ACY-241) / BMS
Trial completion date, Trial primary completion date, Combination therapy: Study of ACY-241 Alone and in Combination With Pomalidomide and Dexamethasone in Multiple Myeloma (clinicaltrials.gov) - Oct 12, 2023
P1a/1b, N=85, Active, not recruiting,
We will evaluate whether PB mononuclear cells have the potential to replace BM as a surrogate for genetic and immunological surveillance in SMM, as we anticipate that further understanding of the immune alterations among patients with SMM and the response to immunomodulatory therapy may provide insight on early intervention and prevention of progression to symptomatic disease. Trial completion date: Jul 2023 --> Jan 2024 | Trial primary completion date: Jun 2023 --> Jan 2024
- |||||||||| citarinostat (ACY-241) / BMS
Journal: Structure and Function of Kdac1, a Class II Deacetylase from the Multidrug-Resistant Pathogen Acinetobacter baumannii. (Pubmed Central) - Sep 20, 2023
We show that Kdac1 catalyzes the deacetylation of free acetyllysine and acetyllysine tetrapeptide assay substrates, and we also report the X-ray crystal structures of unliganded Kdac1 as well as its complex with the hydroxamate inhibitor Citarinostat...Structural comparisons with two other prokaryotic lysine deacetylases reveal conserved residues in the L1 and L12 loops that similarly support tetramer assembly. These studies provide a structural foundation for understanding enzymes that regulate protein function in bacteria through reversible lysine acetylation, serving as a first step in the exploration of these enzymes as possible targets for the development of new antibiotics.
- |||||||||| citarinostat (ACY-241) / BMS, PVX-410 / OncoPep
Enrollment closed, Trial completion date, Trial primary completion date, Epigenetic controller: A Study of PVX-410, a Cancer Vaccine, and Citarinostat +/- Lenalidomide for Smoldering MM (clinicaltrials.gov) - Jan 31, 2023
P1b, N=19, Active, not recruiting,
It was also demonstrated that compared with ACY-241 (a reversible HDAC6 inhibitor in clinical trials), the irreversible HDAC6 selective inhibitor 4 exhibited not only superior anti-multiple myeloma activity but also improved therapeutic index. Recruiting --> Active, not recruiting | Trial completion date: May 2022 --> Jun 2023 | Trial primary completion date: May 2022 --> Jun 2023
- |||||||||| citarinostat (ACY-241) / BMS
Trial completion date, Trial primary completion date, Combination therapy: Study of ACY-241 Alone and in Combination With Pomalidomide and Dexamethasone in Multiple Myeloma (clinicaltrials.gov) - Sep 19, 2022
P1a/1b, N=85, Active, not recruiting,
Trial completion date: Jun 2022 --> Jun 2023 | Trial primary completion date: Jun 2022 --> Jun 2023 Trial completion date: Jun 2022 --> Jul 2023 | Trial primary completion date: Jun 2022 --> Jul 2023
- |||||||||| CRA-026440 / Quest Diagnostics, citarinostat (ACY-241) / BMS
Journal: HDAC8-Selective Inhibition by PCI-34051 Enhances the Anticancer Effects of ACY-241 in Ovarian Cancer Cells. (Pubmed Central) - Aug 22, 2022
Overall, co-inhibition of HDAC6 and HDAC8 through selective inhibitors synergistically suppresses cancer cell proliferation and metastasis in p53 wild-type ovarian cancer cells. These results suggest a novel approach to treating ovarian cancer patients and the therapeutic potential in developing HDAC6/8 dual inhibitors.
- |||||||||| Clinical, Review, Journal, Combination therapy: Targeting cancer epigenetic pathways with small-molecule compounds: Therapeutic efficacy and combination therapies. (Pubmed Central) - Feb 26, 2022
However, lack of potent, selective, and clinically tractable small-molecule compounds makes the strategy to target cancer epigenetic pathways still challenging. Therefore, this review focuses on epigenetic pathways, small molecule inhibitors targeting DNA methyltransferase (DNMT) and small molecule inhibitors targeting histone modification (the main regulatory targets are histone acetyltransferases (HAT), histone deacetylases (HDACs) and histone methyltransferases (HMTS)), as well as the combination strategies of the existing epigenetic therapeutic drugs and more new therapies to improve the efficacy, which will shed light on a new clue on discovery of more small-molecule drugs targeting cancer epigenetic pathways as promising strategies in the future.
- |||||||||| Review, Journal: HDAC6 as privileged target in drug discovery: A perspective. (Pubmed Central) - Nov 21, 2021
Though several HDAC6 inhibitors (HDAC6is) have been developed till date, only two ACY-1215 (ricolinostat) and ACY-241 (citarinostat) are in the clinical trials...This review details the study about the structural biology of HDAC6, its physiological and pathological role in several disease states and the detailed structure-activity relationships (SARs) of the known HDAC6i. This detailed review will provide key insights to design novel and highly effective HDAC6i in the future.
- |||||||||| citarinostat (ACY-241) / BMS
Prolactin drives a dynamic STAT5A/HDAC6/HMGN2 cis -regulatory landscape exploitable in ER+ breast cancer (Hall 1) - Oct 26, 2021 - Abstract #SABCS2021SABCS_1274;
Gene set enrichment analysis identifies significant overlap of ERα regulated genes with genes regulated by prolactin, particularly prolactin regulated genes with promoters or enhancers co-occupied by both STAT5A and HDAC6. Lastly, the therapeutic efficacy of ACY-241 is demonstrated in in vitro and in vivo breast cancer models, where we identify synergistic ACY-241 drug combinations and observe differential sensitivity of ER + models relative to ER - models.
- |||||||||| citarinostat (ACY-241) / BMS
Journal: Prolactin Drives a Dynamic STAT5A/HDAC6/HMGN2 Cis-Regulatory Landscape Exploitable in ER+ Breast Cancer. (Pubmed Central) - Oct 22, 2021
Gene set enrichment analysis identifies significant overlap of ERα regulated genes with genes regulated by prolactin, particularly prolactin regulated genes with promoters or enhancers co-occupied by both STAT5A and HDAC6. Lastly, the therapeutic efficacy of ACY-241 is demonstrated in in vitro and in vivo breast cancer models, where we identify synergistic ACY-241 drug combinations and observe differential sensitivity of ER + models relative to ER - models.
- |||||||||| citarinostat (ACY-241) / BMS, rocilinostat (ACY-1215) / Regenacy, BMS
Journal: PTG-0861: A novel HDAC6-selective inhibitor as a therapeutic strategy in acute myeloid leukaemia. (Pubmed Central) - Apr 7, 2021
In examining compound stability and cellular permeability, PTG-0861 revealed a promising in vitro pharmacokinetic (PK) profile. Altogether, in this study we identified a novel and potent HDAC6-selective inhibitor (∼4× more selective than current clinical standards - citarinostat, ricolinostat), which achieves cellular target engagement, efficacy in hematological cancer cells with a promising safety profile and in vitro PK.
- |||||||||| citarinostat (ACY-241) / BMS, PVX-410 / OncoPep
Trial completion date, Trial primary completion date, Epigenetic controller: A Study of PVX-410, a Cancer Vaccine, and Citarinostat +/- Lenalidomide for Smoldering MM (clinicaltrials.gov) - Feb 24, 2021
P1b, N=20, Recruiting,
Collectively, these findings suggest that the co-inhibition of BET and HDAC6 can be a new therapeutic strategy in HNSCC. Trial completion date: May 2021 --> May 2022 | Trial primary completion date: May 2021 --> May 2022
- |||||||||| paclitaxel / Generic mfg.
Journal, PD(L)-1 Biomarker, IO biomarker: HDAC6-selective inhibitors enhance anticancer effects of paclitaxel in ovarian cancer cells. (Pubmed Central) - Feb 13, 2021
In the present study, a second generation HDAC6-selective inhibitor, ACY-241 (citarinostat), and a novel inhibitor, A452, exhibited synergistic anticancer effects with paclitaxel in AT-rich interaction domain 1A-mutated ovarian cancer in vitro...Treatment with all drug combinations increased the portion of apoptotic cells in fluorescence-activated cell sorting analysis. These results demonstrated synergy between paclitaxel and HDAC6-selective inhibitors, providing further impetus for clinical trials of combination therapy using HDAC6-selective inhibitors, not only in ovarian cancer but also in other tumors.
- |||||||||| citarinostat (ACY-241) / BMS
Preclinical, Journal, PD(L)-1 Biomarker, IO Biomarker: Preclinical validation of Alpha-Enolase (ENO1) as a novel immunometabolic target in multiple myeloma. (Pubmed Central) - Dec 18, 2020
Combination of ENO1i and anti-PD-L1 Ab or HDAC6i ACY-241 enhances autologous MM-specific CD8 CTL activity. Our preclinical data therefore provide the basis for novel immune-based therapeutic approaches targeting ENO1, alone or in combination with anti-PD-L1 Ab or ACY241, to restore anti-MM immunity, enhance MM cytotoxicity, and improve patient outcome.
- |||||||||| citarinostat (ACY-241) / BMS
Trial completion date, Trial primary completion date, Combination therapy: Study of ACY-241 Alone and in Combination With Pomalidomide and Dexamethasone in Multiple Myeloma (clinicaltrials.gov) - Dec 2, 2020
P1a/1b, N=85, Active, not recruiting,
Our preclinical data therefore provide the basis for novel immune-based therapeutic approaches targeting ENO1, alone or in combination with anti-PD-L1 Ab or ACY241, to restore anti-MM immunity, enhance MM cytotoxicity, and improve patient outcome. Trial completion date: Dec 2020 --> Jun 2021 | Trial primary completion date: Dec 2020 --> May 2021
- |||||||||| citarinostat (ACY-241) / BMS, rocilinostat (ACY-1215) / Regenacy, BMS
[VIRTUAL] Design and synthesis of selective HDAC-isoform-targeting small molecule inhibitors (On Demand Oral) - Aug 20, 2020 - Abstract #ACSFall2020ACS-Fall_5438;
In HELA cells, using NanoBRETTM technology, lead compounds showed up to 5-fold greater residence time with the HDAC6 target, as well as selectivity relative to HDAC1In addition, lead compounds showed potent biological activity in the same cell lines, and at the same time, showed limited toxicity against a range of healthy cells, included pooled human fibroblasts and hematopoietic stem cells, with large therapeutic indexes of >100. Notably, lead HDAC6 inhibitors presented exhibit excellent pharmacokinetic properties with greater Cmax, t1/2, AUC, and MRT than ACY-241.
- |||||||||| bortezomib / Generic mfg., citarinostat (ACY-241) / BMS, rocilinostat (ACY-1215) / Regenacy, BMS
Preclinical evaluation of novel HDAC6 selective inhibitors CVL608 with potent in vitro and in vivo profiles in tumors (Virtual Meeting II: E-Posters) - May 16, 2020 - Abstract #AACRII2020AACR-II_3041;
Moreover, CVL608 in combination with Bortezomib (0.5 mg/kg) significate inhibit tumor growth compared with monotherapy and ACY-241+Bortezomib (p<0.05). CVL608 monotherapy and in combination with PTX in MCF-7 CDX, and in combination with PD-1 inhibitor in LL/2(LLC1) and B16F10 CDX models are under investigating.These data may support interest in the clinical development of novel HDAC6 selective inhibitors in both non-solid tumor and solid tumors.
- |||||||||| citarinostat (ACY-241) / BMS
Trial completion date, Trial primary completion date, Combination therapy: Study of ACY-241 Alone and in Combination With Pomalidomide and Dexamethasone in Multiple Myeloma (clinicaltrials.gov) - Apr 9, 2020
P1a/1b, N=85, Active, not recruiting,
CVL608 monotherapy and in combination with PTX in MCF-7 CDX, and in combination with PD-1 inhibitor in LL/2(LLC1) and B16F10 CDX models are under investigating.These data may support interest in the clinical development of novel HDAC6 selective inhibitors in both non-solid tumor and solid tumors. Trial completion date: Jun 2020 --> Jan 2021 | Trial primary completion date: Jun 2020 --> Oct 2020
- |||||||||| citarinostat (ACY-241) / BMS, rocilinostat (ACY-1215) / Regenacy, BMS
Clinical, Journal, PD(L)-1 Biomarker, IO biomarker: HDAC6 selective inhibition of melanoma patient T-cells augments anti-tumor characteristics. (Pubmed Central) - Apr 1, 2020
Trial completion date: Jun 2020 --> Jan 2021 | Trial primary completion date: Jun 2020 --> Oct 2020 HDAC6-selective inhibitors augmented melanoma patient T-cell immune properties, providing a rationale for translational investigation assessing their potential clinical efficacy.
- |||||||||| citarinostat (ACY-241) / BMS, Opdivo (nivolumab) / BMS
Enrollment closed, Enrollment change, Trial completion date, Trial primary completion date, Combination therapy, PD(L)-1 Biomarker: Selective HDAC6 Inhibitor ACY 241 in Combination With Nivolumab in Patients With Unresectable Non Small Cell Lung Cancer (clinicaltrials.gov) - Feb 27, 2020
P1b, N=16, Active, not recruiting,
HDAC6-selective inhibitors augmented melanoma patient T-cell immune properties, providing a rationale for translational investigation assessing their potential clinical efficacy. Recruiting --> Active, not recruiting | N=41 --> 16 | Trial completion date: Dec 2019 --> Jul 2020 | Trial primary completion date: Nov 2019 --> Jul 2020
- |||||||||| citarinostat (ACY-241) / BMS
Trial completion, Combination therapy, Metastases: ACY 241 in Combination With Paclitaxel in Patients With Advanced Solid Tumors (clinicaltrials.gov) - Feb 26, 2020
P1b, N=20, Completed,
Recruiting --> Active, not recruiting | N=41 --> 16 | Trial completion date: Dec 2019 --> Jul 2020 | Trial primary completion date: Nov 2019 --> Jul 2020 Active, not recruiting --> Completed
- |||||||||| citarinostat (ACY-241) / BMS
Preclinical Validation of Alpha-Enolase (ENO1) As a Novel Immunometabolic Target in Multiple Myeloma (Valencia D (W415D), Level 4 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_5165;
Finally, the combination of ENOi and ACY-241 also enhances anti-MM immune responses (% MM lysis: ENO1i: 35%; ENO1i + ACY-241: 54%; n = 8; p = 0.0044) . Conclusions Our preclinical data provide the basis for novel immune-based therapeutic approaches targeting immunosuppressive metabolic alpha-enolase enzyme ENO1 to restore anti-MM immunity and improve patient outcome.
- |||||||||| citarinostat (ACY-241) / BMS
Trial completion date, Trial primary completion date, Combination therapy: Study of ACY-241 Alone and in Combination With Pomalidomide and Dexamethasone in Multiple Myeloma (clinicaltrials.gov) - Oct 17, 2019
P1a/1b, N=85, Active, not recruiting,
These data highlight the potential of combining avadomide with a HDAC inhibitor such as citarinostat in DLBCL. Trial completion date: Jul 2020 --> Dec 2019 | Trial primary completion date: Jul 2020 --> Dec 2019
- |||||||||| citarinostat (ACY-241) / BMS
Enrollment closed, Enrollment change, Trial completion date, Trial primary completion date, Combination therapy, Metastases: ACY 241 in Combination With Paclitaxel in Patients With Advanced Solid Tumors (clinicaltrials.gov) - Jun 12, 2019
P1b, N=20, Active, not recruiting,
Trial completion date: Dec 2018 --> Dec 2019 | Trial primary completion date: Dec 2018 --> Nov 2019 Recruiting --> Active, not recruiting | N=41 --> 20 | Trial completion date: Jul 2018 --> Dec 2019 | Trial primary completion date: Jul 2018 --> Nov 2019
- |||||||||| citarinostat (ACY-241) / BMS
Trial completion date, Trial primary completion date, Combination therapy: Study of ACY-241 Alone and in Combination With Pomalidomide and Dexamethasone in Multiple Myeloma (clinicaltrials.gov) - Apr 23, 2019
P1a/1b, N=85, Active, not recruiting,
These studies therefore demonstrate mechanisms whereby ACY241 augments immune response, providing the rationale for its use, alone and in combination, to restore host anti-tumor immunity and improve patient outcome. Trial completion date: Jul 2019 --> Jul 2020 | Trial primary completion date: Jan 2019 --> Jul 2020
- |||||||||| citarinostat (ACY-241) / BMS, PVX-410 / OncoPep
Trial completion date, Trial primary completion date, Epigenetic controller: A Study of PVX-410, a Cancer Vaccine, and Citarinostat +/- Lenalidomide for Smoldering MM (clinicaltrials.gov) - Jul 16, 2018
P1b, N=20, Active, not recruiting,
Active, not recruiting --> Recruiting Trial completion date: Sep 2021 --> May 2021 | Trial primary completion date: Sep 2019 --> May 2021
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