- |||||||||| verapamil / Generic mfg., sildenafil / Generic mfg., nintedanib / Generic mfg.
Journal: Pan-transcriptome-based candidate therapeutic discovery for idiopathic pulmonary fibrosis. (Pubmed Central) - Sep 17, 2021
There are two US Food and Drug Administration (FDA)-approved drugs, pirfenidone and nintedanib, for treatment of patients with idiopathic pulmonary fibrosis (IPF)...Among these compounds are multiple receptor kinase inhibitors (e.g. nintedanib, currently approved for IPF, and sunitinib), aurora kinase inhibitor (barasertib), epidermal growth factor receptor inhibitors (erlotinib, gefitinib), calcium channel blocker (verapamil), phosphodiesterase inhibitors (roflumilast, sildenafil), PPAR agonists (pioglitazone), histone deacetylase inhibitors (entinostat), and opioid receptor antagonists (nalbuphine)...As about half of the candidates discovered in this study are either FDA-approved or are currently in clinical trials for other diseases, rapid translation of these compounds as potential IPF therapeutics is possible. Further, the integrative connectivity analysis framework in this study can be adapted in early phase drug discovery for other common and rare diseases with transcriptomic profiles.The reviews of this paper are available via the supplemental material section.
- |||||||||| entinostat (SNDX-275) / Kyowa Kirin, Syndax Pharma
[VIRTUAL] Epigenetic modulation of neuroblastoma enhances T- and NK cell immunogenicity via induction of surface expression of MHC class I and MICA/MICB () - Sep 16, 2021 - Abstract #ITOC2021ITOC_120;
Intriguingly, co-culture of NBL cells with tumor-specific T cells and healthy-donor NK cells upon treatment with the HDACi Entinostat resulted in enhanced in vitro T- and NK cell activation and cytotoxicity...Pre-treatment of NBL with HDACi resulted in enhanced in vitro T- and NK cell mediated cytotoxicity, substantiating HDACi as a potential strategy to improve adaptive immune engagement and therewith immunogenicity to aid NBL treatment. This work was supported by the Villa Joep Foundation [IWOV-Actief.51391.180034].
- |||||||||| entinostat (SNDX-275) / Kyowa Kirin, Syndax Pharma
Journal, Epigenetic controller: Efficient Synthesis and Bioevaluation of Novel Dual Tubulin/Histone Deacetylase 3 Inhibitors as Potential Anticancer Agents. (Pubmed Central) - Aug 27, 2021
Novel dual HDAC3/tubulin inhibitors were designed and efficiently synthesized by combining the pharmacophores of SMART (tubulin inhibitor) and MS-275 (HDAC inhibitor), among which compound 15c was found to be the most potent and balanced HDAC3/tubulin dual inhibitor with high HDAC3 activity (IC = 30 nM) and selectivity (SI > 1000) as well as excellent antiproliferative potency against various cancer cell lines, including an HDAC-resistant gastric cancer cell line (YCC3/7) with IC values in the range of 30-144 nM...Finally, 15c presented a safe cardiotoxicity profile and did not cause nephro-/hepatotoxicity. Collectively, this work shows that compound 15c represents a novel tubulin/HDAC3 dual-targeting agent deserving further investigation as a potential anticancer agent.
- |||||||||| entinostat (SNDX-275) / Kyowa Kirin, Syndax Pharma
Biomarker, Journal: The MT1G Gene in LUHMES Neurons Is a Sensitive Biomarker of Neurotoxicity. (Pubmed Central) - Aug 22, 2021
LUHMES immortalized human dopaminergic neurons were surveyed by RNA sequencing following challenge with parkinsonian toxicants rotenone, 6-hydroxydopamine, MPP+, and ziram (zinc dimethyldithiocarbamate; ZnDDC), as well as additional toxicants paraquat, MS275, and methylmercury...Metals and chelators that caused dynamic increases in MT1G expression also caused cytotoxicity, except NiDDC induced MT1G at 5 μM, but lacked cytotoxicity up to 100 μM. These results bolster prior work suggesting that neurons are characteristically sensitive to depletion of glutathione or to disruption of cellular metal distribution and provide biomarkers to search for such neurotoxicants in chemical libraries.
- |||||||||| mocetinostat (MGCD0103) / Mirati, Otsuka, entinostat (SNDX-275) / Kyowa Kirin, Syndax Pharma
Journal: Network-based analysis of fatal comorbidities of COVID-19 and potential therapeutics. (Pubmed Central) - Aug 21, 2021
Among them, COL-3 had earlier shown activity against acute lung injury and acute respiratory distress, while entinostat and mocetinostat have been investigated for non-small-cell lung cancer. We propose that these drugs can be repurposed for COVID-19.
- |||||||||| Xtandi (enzalutamide capsule) / Pfizer, Astellas, Jingzhuda (entinostat) / EOC Pharma, EddingPharm
Enrollment change, Trial completion date, Trial termination, Trial primary completion date, Combination therapy, Metastases: Combination of Entinostat and Enzalutamide in Advanced Prostate Cancer (clinicaltrials.gov) - Aug 18, 2021
P1, N=6, Terminated,
N=36 --> 21 | Trial primary completion date: Jun 2022 --> Jun 2021 N=18 --> 6 | Trial completion date: Nov 2024 --> Sep 2020 | Recruiting --> Terminated | Trial primary completion date: Nov 2022 --> Sep 2020; Sponsor discontinued the drug
- |||||||||| entinostat (SNDX-275) / Kyowa Kirin, Syndax Pharma, Nexavar (sorafenib) / Bayer, Amgen
Journal, PD(L)-1 Biomarker, IO biomarker: The multi-kinase inhibitor lenvatinib interacts with the HDAC inhibitor entinostat to kill liver cancer cells. (Pubmed Central) - Aug 11, 2021
P1
Knock down of HDACs1/2/3 prevented the lenvatinib and entinostat combination from regulating PD-L1 and MHCA expression. Collectively, our data demonstrate that lenvatinib and entinostat interact to kill liver cancer cells via ROS-dependent activation of ATM and inactivation of eIF2α, resulting in greater levels of toxic autophagosome formation and reduced expression of protective mitochondrial proteins.
- |||||||||| bintrafusp alfa (M7824) / EMD Serono, PDS01ADC / PDS Biotech, Jingzhuda (entinostat) / EOC Pharma, EddingPharm
Enrollment open, Metastases: A Phase I/II Study of Combination Immunotherapy for Advanced Cancers Including HPV-Associated Malignancies, Small Bowel, and Colon Cancers (clinicaltrials.gov) - Aug 5, 2021
P1/2, N=70, Recruiting,
Based on PK and PD, the R2PD in pediatric patients with solid tumors is 4 mg/m orally administered once weekly. Not yet recruiting --> Recruiting
- |||||||||| entinostat (SNDX-275) / Kyowa Kirin, Syndax Pharma
Clinical, Journal: Drug repositioning based on network-specific core genes identifies potential drugs for the treatment of autism spectrum disorder in children. (Pubmed Central) - Jul 27, 2021
We found a total of 42 candidate drugs that were associated with mental illness, among which 10 drugs (baclofen, sulpiride, estradiol, entinostat, everolimus, fluvoxamine, curcumin, calcitriol, metronidazole, and zinc) were postulated to be associated with ASD. This study proposes a powerful network-based drug repositioning framework and also provides candidate drugs as well as potential drug targets for the subsequent development of ASD therapeutic drugs.
- |||||||||| entinostat (SNDX-275) / Kyowa Kirin, Syndax Pharma
Journal, Epigenetic controller: A novel histone deacetylase inhibitor MPT0L184 dysregulates cell-cycle checkpoints and initiates unscheduled mitotic signaling. (Pubmed Central) - Jul 24, 2021
In this study, we report a selective entinostat derivative, MPT0L184, with potent cancer-killing activity in both cell-based and mouse xenograft models...Furthermore, gastric cancer cells resistant to HDAC inhibitors were vulnerable to MPT0L184. Taken together, our study discovers MPT0L184 as a novel HDAC inhibitor that can trigger premature mitosis and potentially counteract drug resistance of cancers.
- |||||||||| entinostat (SNDX-275) / Kyowa Kirin, Syndax Pharma, Opdivo (nivolumab) / Ono Pharma, BMS, Yervoy (ipilimumab) / Ono Pharma, BMS
[VIRTUAL] Entinostat, nivolumab and ipilimumab in advanced HER2-negative breast cancer (ETCTN-9844) (Channel 2) - Jul 22, 2021 - Abstract #ESMO2021ESMO_1317;
An ORR of 30% suggests this combination should be evaluated further. Correlative analyses from serial biospecimens pre- and post-therapy to evaluate the immune response and landscape will be presented.
- |||||||||| entinostat (SNDX-275) / Kyowa Kirin, Syndax Pharma
Preclinical, Journal: Immunological discrepancy in aged mice facilitates skin allograft survival. (Pubmed Central) - Jul 22, 2021
In conclusion, allogeneic immunity was different in aged from young mice in high frequency of MDSC and high serum level of TGF-β. Blocking the function of MDSC reversed the low immunity in aged mice and caused skin allograft rejection similar to young recipients.
- |||||||||| entinostat (SNDX-275) / Kyowa Kirin, Syndax Pharma
Journal, IO biomarker, Epigenetic controller: Class I histone deacetylase inhibition promotes CD8 T cell activation in ovarian cancer. (Pubmed Central) - Jul 21, 2021
Our findings suggest class I HDAC inhibition can promote activation of intratumoral CD8 T cells, potentially by compromising suppressive networks within the EOC tumor microenvironment. In this manner, class I HDAC inhibition might render advanced-stage EOC susceptible to immunotherapeutic treatment modalities.
- |||||||||| erastin - Whitehead Institute for Biomedical Research, Dana / Farber Cancer Institute, Columbia University, Prolexys, entinostat (SNDX-275) / Kyowa Kirin, Syndax Pharma, sapanisertib (TAK-228) / Takeda
[VIRTUAL] SCREENING OF A DRUG-LIBRARY IN HDAC-2 PROFICIENT AND DEFICIENT MURINE PANCREATIC DUCTAL ADENOCARCINOMA CELLS TO IDENTIFY NEW POTENTIAL COMBINATION THERAPIES (Poster Exhibition) - Jul 20, 2021 - Abstract #UEGW2021UEGW_4940;
Based on our calculation, we defined BX-795, GSK503, JIB-04, Sapanisertib and Erastin as hits and further evaluated the relevance of Erastin. Based on our data, HDAC inhibitors like Entinostat are synergistic with the ferroptosis-inducer Erastin and should be further advanced in preclinical models.
- |||||||||| erastin - Whitehead Institute for Biomedical Research, Dana / Farber Cancer Institute, Columbia University, Prolexys, entinostat (SNDX-275) / Kyowa Kirin, Syndax Pharma, sapanisertib (TAK-228) / Takeda
[VIRTUAL] SCREENING OF A DRUG-LIBRARY IN HDAC-2 PROFICIENT AND DEFICIENT MURINE PANCREATIC DUCTAL ADENOCARCINOMA CELLS TO IDENTIFY NEW POTENTIAL COMBINATION THERAPIES (Poster Exhibition) - Jul 20, 2021 - Abstract #UEGW2021UEGW_2760;
Based on our calculation, we defined BX-795, GSK503, JIB-04, Sapanisertib and Erastin as hits and further evaluated the relevance of Erastin. Based on our data, HDAC inhibitors like Entinostat are synergistic with the ferroptosis-inducer Erastin and should be further advanced in preclinical models.
- |||||||||| erastin - Whitehead Institute for Biomedical Research, Dana / Farber Cancer Institute, Columbia University, Prolexys, entinostat (SNDX-275) / Kyowa Kirin, Syndax Pharma, sapanisertib (TAK-228) / Takeda
[VIRTUAL] SCREENING OF A DRUG-LIBRARY IN HDAC-2 PROFICIENT AND DEFICIENT MURINE PANCREATIC DUCTAL ADENOCARCINOMA CELLS TO IDENTIFY NEW POTENTIAL COMBINATION THERAPIES (Poster Exhibition) - Jul 20, 2021 - Abstract #UEGW2021UEGW_929;
Based on our calculation, we defined BX-795, GSK503, JIB-04, Sapanisertib and Erastin as hits and further evaluated the relevance of Erastin. Based on our data, HDAC inhibitors like Entinostat are synergistic with the ferroptosis-inducer Erastin and should be further advanced in preclinical models.
- |||||||||| Jingzhuda (entinostat) / EOC Pharma, EddingPharm, Lynparza (olaparib) / Merck (MSD), AstraZeneca
Trial completion date, Trial primary completion date: Olaparib and Entinostat in Patients With Recurrent, Platinum-Refractory, Resistant Ovarian, Primary Peritoneal, Fallopian Tube Cancers (clinicaltrials.gov) - Jul 15, 2021
P1/2, N=73, Recruiting,
We demonstrate that MS-275 inhibits histone deacetylation and alleviates colitis by ameliorating inflammation, reducing apoptosis, and maintaining intestinal epithelial barrier via VDR, providing new strategies for UC treatment. Trial completion date: Sep 2025 --> Sep 2026 | Trial primary completion date: Sep 2023 --> Sep 2024
- |||||||||| Avastin (bevacizumab) / Roche, Jingzhuda (entinostat) / EOC Pharma, EddingPharm, Tecentriq (atezolizumab) / Roche
Enrollment closed, Enrollment change, Trial completion date, Trial primary completion date, Combination therapy, Metastases: Atezolizumab in Combination With Entinostat and Bevacizumab in Patients With Advanced Renal Cell Carcinoma (clinicaltrials.gov) - Jul 14, 2021
P1/2, N=29, Active, not recruiting,
Trial completion date: Sep 2025 --> Sep 2026 | Trial primary completion date: Sep 2023 --> Sep 2024 Recruiting --> Active, not recruiting | N=62 --> 29 | Trial completion date: Jan 2021 --> Dec 2022 | Trial primary completion date: Jan 2020 --> Dec 2021
- |||||||||| Jingzhuda (entinostat) / EOC Pharma, EddingPharm
Enrollment closed, Trial completion date, Trial primary completion date, Combination therapy, Metastases: EOC103A3101: Ph3 Study of Exemestane With or Without Entinostat in Chinese Patients With Hormone Receptor-Positive, Locally Advanced or Metastatic Breast Cancer (clinicaltrials.gov) - Jul 9, 2021
P3, N=375, Active, not recruiting,
Recruiting --> Active, not recruiting | N=62 --> 29 | Trial completion date: Jan 2021 --> Dec 2022 | Trial primary completion date: Jan 2020 --> Dec 2021 Recruiting --> Active, not recruiting | Trial completion date: Aug 2021 --> Mar 2023 | Trial primary completion date: Feb 2021 --> Jul 2021
- |||||||||| entinostat (SNDX-275) / Kyowa Kirin, Syndax Pharma
Journal, Epigenetic controller: Histone deacetylase 1 (HDAC1): A key player of T cell-mediated arthritis. (Pubmed Central) - Jul 7, 2021
Accordingly, analysis of human RNA-sequencing (RNA-seq) data and histological analysis of synovial tissue samples from human RA patients revealed the existence of CD4CCR6 cells with enhanced HDAC1 expression. Our data indicate a key role for HDAC1 for the pathogenesis of CIA and suggest that HDAC1 and other class I HDACs might be promising targets of selective HDAC inhibitors (HDACi) for the treatment of RA.
- |||||||||| Keytruda (pembrolizumab) / Merck (MSD), Jingzhuda (entinostat) / EOC Pharma, EddingPharm
Trial completion date, Trial primary completion date, Combination therapy, Epigenetic controller: Testing the Safety and Efficacy of the Combination of the Antibody Pembrolizumab and Entinostat in Patients With Myelodysplastic Syndrome Who Are Not Responding to Hypomethylating Agents (clinicaltrials.gov) - Jul 2, 2021
P1b, N=27, Active, not recruiting,
Our data indicate a key role for HDAC1 for the pathogenesis of CIA and suggest that HDAC1 and other class I HDACs might be promising targets of selective HDAC inhibitors (HDACi) for the treatment of RA. Trial completion date: Jun 2021 --> Jun 2022 | Trial primary completion date: Jun 2021 --> Jun 2022
- |||||||||| Biomarker, Trial completion date, Trial primary completion date: Beat AML: Study of Biomarker-Based Treatment of Acute Myeloid Leukemia (clinicaltrials.gov) - Jun 29, 2021
P1/2, N=2000, Recruiting,
Trial completion date: Jun 2021 --> Jun 2022 | Trial primary completion date: Jun 2021 --> Jun 2022 Trial completion date: Dec 2021 --> Dec 2023 | Trial primary completion date: Dec 2021 --> Dec 2023
- |||||||||| entinostat (SNDX-275) / Kyowa Kirin, Syndax Pharma
Journal, Epigenetic controller: The potential for histone deacetylase (HDAC) inhibitors as cestocidal drugs. (Pubmed Central) - Jun 26, 2021
Due to the maximum dose approved for entinostat, adjustments in the dose regime and/or combinations with currently-used anthelmintic drugs are needed, and the selectivity of TH65 and TH92 towards parasite targets should be assessed. The results presented here suggest that HDAC inhibitors represent novel and potent drug candidates against cestodes and pave the way to understanding the roles of HDACs in these parasites.
- |||||||||| Review, Journal, Epigenetic controller: Targeting histone acetylation in pulmonary hypertension and right ventricular hypertrophy. (Pubmed Central) - Jun 22, 2021
Due to the reversible nature of post-translational protein acetylation, the therapeutic efficacy of numerous small-molecule inhibitors (Vorinostat, Valproic acid, Sodium butyrate, Mocetinostat, Entinostat, Tubastatin A, Apabetalone, JQ1, Resveratrol) have been evaluated in different pre-clinical models of cardiovascular disease, which revealed the promising therapeutic benefits of targeting histone acetylation pathways in the attenuation of cardiac hypertrophy, fibrosis, left heart dysfunction, PH and RHF. This review also emphasizes the need for deeper molecular insights into the contribution of epigenetic changes to PH pathogenesis, and therapeutic evaluation of isoform-specific modulation in ex vivo and in vivo models of PH and RHF.
- |||||||||| decitabine / Generic mfg.
Clinical, Journal: Clinical efficiency of epigenetic drugs therapy in bone malignancies. (Pubmed Central) - Jun 22, 2021
To enhance the therapeutic effect, the prevalent approach in phase II trial is the association of these epigenetic drug inhibitors, with targeted therapy or immune checkpoint blockade. Optimization of drug dosing and regimens of phase II trials may improve the clinical efficiency of such novel therapeutic approaches against these devastating cancers.
- |||||||||| entinostat (SNDX-275) / Kyowa Kirin, Syndax Pharma, BMS-345541 / BMS
Journal: The Utility of Resolving Asthma Molecular Signatures Using Tissue-Specific Transcriptome Data. (Pubmed Central) - Jun 22, 2021
While most of the existing literature describes asthma transcriptome data from individual sample types, the present work demonstrates the utility of multi-tissue transcriptome data. Future studies should focus on collecting transcriptomic data from multiple tissues, age and race groups, genetic background, disease subtypes and on the availability of better-annotated data in the public domain.
- |||||||||| Farydak (panobinostat) / Novartis, entinostat (SNDX-275) / Kyowa Kirin, Syndax Pharma, givinostat (ITF2357) / Italfarmaco
Preclinical, Journal: Treatment with non-specific HDAC inhibitors administered after disease onset does not delay evolution in a mouse model of progressive multiple sclerosis. (Pubmed Central) - Jun 5, 2021
When put into a clinical context, for the first time data cast doubt on the relevance of HDACi to treatment of progressive MS (PMS). Also, our findings further indicate that, akin to PMS, neuropathogensis of PEAE in NOD mice becomes independent from autoimmunity, thereby corroborating the relevance of this model to experimental PMS research.
- |||||||||| Jingzhuda (entinostat) / EOC Pharma, EddingPharm
Trial completion, Surgery: NRG-GY011: Medroxyprogesterone Acetate With or Without Entinostat Before Surgery in Treating Patients With Endometrioid Endometrial Cancer (clinicaltrials.gov) - Jun 2, 2021
P1, N=50, Completed,
Also, our findings further indicate that, akin to PMS, neuropathogensis of PEAE in NOD mice becomes independent from autoimmunity, thereby corroborating the relevance of this model to experimental PMS research. Active, not recruiting --> Completed
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