- |||||||||| entinostat (SNDX-275) / Kyowa Kirin, Syndax Pharma
Journal: Inhibition of HDAC1 alleviates monocrotaline-induced pulmonary arterial remodeling through up-regulation of miR-34a. (Pubmed Central) - Jan 29, 2022
HDAC1 contributes to the development of MCT-induced rat PAH by suppressing miR-34a level and subsequently up-regulating the ratio of MMP-9/TIMP-1 and MMP-2/TIMP-2. Inhibition of HDAC1 alleviates pulmonary arterial remodeling and PAH through up-regulation of miR-34a level and subsequent reduction of MMP-9/TIMP-1 and MMP-2/TIMP-2, suggesting that inhibition of HDAC1 might have potential value in the management of PAH.
- |||||||||| Zolinza (vorinostat) / Merck (MSD), entinostat (SNDX-275) / Kyowa Kirin, Syndax Pharma
Preclinical, Journal: Design, synthesis and biological evaluation of novel o-aminobenzamide derivatives as potential anti-gastric cancer agents in vitro and in vivo. (Pubmed Central) - Jan 27, 2022
Therefore, to explore new oral chemical entities with high efficiency and low toxicity, 41 o-aminobenzamide derivatives based on the scaffolds of MS-275 and SAHA were designed, synthesized, and evaluated for their anti-gastric cancer abilities in vitro and in vivo...What is worth mentioning is that compound F8 was more efficient and less toxic than the positive drug capecitabine in vivo on the HGC-27-xenograft model...Besides, western blotting analysis, IHC analysis, differentially expressed proteins analysis and ABPP experiment indicated that compound F8 could modulate molecular pathways involved in apoptosis and cell cycle progression. Consequently, compound F8 is a strong candidate for the development of human gastric cancer therapy.
- |||||||||| entinostat (SNDX-275) / Kyowa Kirin, Syndax Pharma
Biomarker, Journal: Inhibition of class I HDACs preserves hair follicle inductivity in postnatal dermal cells. (Pubmed Central) - Jan 27, 2022
In addition, the inhibition of class I HDACs activates the Wnt signaling pathway, the most well-described molecular pathway in HF development, via increased histone H3 acetylation within the promoter region of the Wnt transcription factor LEF1. Our results suggest that class I HDACs could be a potential target for the neogenesis of HFs.
- |||||||||| entinostat (SNDX-275) / Kyowa Kirin, Syndax Pharma
Journal: Entinostat improves acute neurological outcomes and attenuates hematoma volume after Intracerebral Hemorrhage. (Pubmed Central) - Jan 19, 2022
Consistently, the expression of proinflammatory microglial/macrophage marker, CD16/32, was remarkably reduced in Entinostat treated group after ICH in comparison to control. Altogether, data implicates the potential of class1 histone deacetylase inhibitor, Entinostat, in improving acute neurological function after ICH warranting further investigation.
- |||||||||| entinostat (SNDX-275) / Kyowa Kirin, Syndax Pharma
Journal: HDAC inhibitor, MS-275, increases vascular permeability by suppressing Robo4 expression in endothelial cells. (Pubmed Central) - Jan 14, 2022
Taken together, we demonstrated that MS-275 suppresses Robo4 expression by inhibiting HDAC3 in endothelial cells and enhances endothelial and vascular permeability. Thus, we demonstrated a novel mechanism regulating Robo4 expression and vascular permeability, which is anticipated to contribute to future therapies for infectious and inflammatory diseases.
- |||||||||| entinostat (SNDX-275) / Kyowa Kirin, Syndax Pharma
Clinical, P1 data, Journal, Epigenetic controller: Phase I Study and Pilot Efficacy Analysis of Entinostat, a Novel Histone Deacetylase Inhibitor, in Chinese Postmenopausal Women with Hormone Receptor-Positive Metastatic Breast Cancer. (Pubmed Central) - Jan 14, 2022
P1
Entinostat with exemestane showed reasonable safety, tolerability, and encouraging efficacy in Chinese patients with HR+/HER2- MBC. These results support further evaluation in a randomized, double-blind Phase III study with a weekly 5 mg entinostat dose in a Chinese population.
- |||||||||| entinostat (SNDX-275) / Kyowa Kirin, Syndax Pharma
Journal, Combination therapy, Epigenetic controller: GM101 in Combination with Histone Deacetylase Inhibitor Enhances Anti-Tumor Effects in Desmoplastic Microenvironment. (Pubmed Central) - Jan 14, 2022
Four different HDACi (suberohydroxamic acid (SBHA), MS-275, trichostatin A (TSA), and valproic acid) candidates in combination with replication-incompetent and GFP-expressing Ad (dAd/GFP) revealed that SBHA and MS-275 exerted more potent enhancement in Ad transduction efficacy than TSA or valproic acid...Potent antitumor efficacy was achieved via the combination of GM101 with HDACi, inducing necrotic and apoptotic cancer cell death, inhibiting cancer cell proliferation, degrading ECM in tumor tissue, and thus exerting the highest level of virus dispersion and accumulation. Collectively, these data demonstrate that the combination of GM101 and HDACi can enhance intratumoral dispersion and accumulation of oAd through multifaced mechanisms, making it a promising strategy to address the challenges toward successful clinical development of oAd.
- |||||||||| Journal: E-Cadherin-Deficient Epithelial Cells Are Sensitive to HDAC Inhibitors. (Pubmed Central) - Jan 12, 2022
Finally, entinostat enhanced Cdh1 expression in heterozygous Cdh1 murine organoids. In conclusion, entinostat is a promising drug for the chemoprevention and/or treatment of HDGC and may also be beneficial for the treatment of sporadic CDH1-deficient cancers.
- |||||||||| Jingzhuda (entinostat) / EOC Pharma, EddingPharm, Opdivo (nivolumab) / BMS, Yervoy (ipilimumab) / BMS
Trial completion date, Trial primary completion date, Combination therapy: Study of Entinostat With Nivolumab Plus Ipilimumab in Previously Treated Renal Cell Carcinoma (clinicaltrials.gov) - Jan 12, 2022
P2, N=18, Active, not recruiting,
In conclusion, entinostat is a promising drug for the chemoprevention and/or treatment of HDGC and may also be beneficial for the treatment of sporadic CDH1-deficient cancers. Trial completion date: Aug 2021 --> Aug 2023 | Trial primary completion date: Aug 2021 --> Aug 2022
- |||||||||| entinostat (SNDX-275) / Kyowa Kirin, Syndax Pharma
Journal: Targeting an inducible SALL4-mediated cancer vulnerability with sequential therapy. (Pubmed Central) - Jan 11, 2022
DAC pretreatment sensitized SALL4-negative cancer cells to entinostat, which negatively affected SALL4 expression through a microRNA, miRNA-205, both in culture and in vivo...Moreover, SALL4 was essential for the efficiency of sequential treatment of DAC and Entinostat. Overall, this proof-of-concept study provides a framework whereby the targeting pathways such as SALL4-centered therapy can be expanded, sensitizing cancer cells to treatment by transient target induction and engineering a dependency.
- |||||||||| Jingzhuda (entinostat) / EOC Pharma, EddingPharm, Opdivo (nivolumab) / BMS, Yervoy (ipilimumab) / BMS
Trial primary completion date, IO biomarker, Surgery, Metastases: ETCTN-9844: Entinostat, Nivolumab, and Ipilimumab in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery or Locally Advanced or Metastatic HER2-Negative Breast Cancer (clinicaltrials.gov) - Jan 6, 2022
P1, N=45, Active, not recruiting,
Overall, this proof-of-concept study provides a framework whereby the targeting pathways such as SALL4-centered therapy can be expanded, sensitizing cancer cells to treatment by transient target induction and engineering a dependency. Trial primary completion date: Dec 2021 --> Dec 2022
- |||||||||| Jingzhuda (entinostat) / EOC Pharma, EddingPharm, Tecentriq (atezolizumab) / Roche
Enrollment closed, Combination therapy: Testing the Addition of an Anti-cancer Drug, Entinostat, to the Usual Chemotherapy and Immunotherapy Treatment (Atezolizumab, Carboplatin and Etoposide) for Previously Untreated Aggressive Lung Cancer That Has Spread (clinicaltrials.gov) - Jan 5, 2022
P1, N=36, Active, not recruiting,
Trial primary completion date: Dec 2021 --> Dec 2022 Suspended --> Active, not recruiting
- |||||||||| entinostat (SNDX-275) / Kyowa Kirin, Syndax Pharma, Lynparza (olaparib) / Merck (MSD), AstraZeneca
Journal, BRCA Biomarker, PARP Biomarker: Entinostat, a selective HDAC1/2 inhibitor, potentiates the effects of olaparib in homologous recombination proficient ovarian cancer. (Pubmed Central) - Jan 1, 2022
Entinostat inhibits HR repair by reducing BRCA1 expression and stalling replication fork progression, leading to irreparable DNA damage and ultimate cell death. This work provides preclinical support for the clinical trial of the combination of olaparib and entinostat in HR-proficient ovarian cancer and suggests potential benefit even for CCNE1 amplified subtypes.
- |||||||||| azacitidine / Generic mfg.
Journal: HDAC inhibitors induce LIFR expression and promote a dormancy phenotype in breast cancer. (Pubmed Central) - Jan 1, 2022
Recent Phase II clinical trial data studying entinostat and azacitidine in metastatic breast cancer revealed that induction of several pro-dormancy genes post-treatment was associated with prolonged patient survival. Together, these findings suggest HDACi as a potential therapeutic avenue to promote dormancy, prevent recurrence, and improve patient outcomes in breast cancer.
- |||||||||| Jingzhuda (entinostat) / EOC Pharma, EddingPharm, Opdivo (nivolumab) / BMS
Trial completion, Combination therapy, Metastases: A Clinical Trial of Entinostat in Combination With Nivolumab for Patients With Previously Treated Unresectable or Metastatic Cholangiocarcinoma and Pancreatic Adenocarcinoma (clinicaltrials.gov) - Dec 16, 2021
P2, N=44, Completed,
Retreatment, rechallenge and escalation are available options for patients with melanoma who relapse in the adjuvant or advanced setting. Active, not recruiting --> Completed
- |||||||||| irinotecan / Generic mfg.
Preclinical, Journal, Epigenetic controller: Class 1 Histone Deacetylases and Ataxia-Telangiectasia Mutated Kinase Control the Survival of Murine Pancreatic Cancer Cells upon dNTP Depletion. (Pubmed Central) - Dec 16, 2021
We used clinically relevant doses of hydroxyurea and the class 1 HDAC inhibitor entinostat...Regarding the induction of apoptosis and DNA replication stress, hydroxyurea and the novel RNR inhibitor COH29 are superior to the topoisomerase-1 inhibitor irinotecan which is used to treat PDAC...Unlike in other cell systems, ATM is pro-apoptotic in hydroxyurea-treated murine PDAC cells. These data reveal novel insights into a cytotoxic, ATM-regulated, and HDAC-dependent replication stress program in PDAC cells.
- |||||||||| mocetinostat (MGCD0103) / Mirati, Otsuka, entinostat (SNDX-275) / Kyowa Kirin, Syndax Pharma
Biomarker, Preclinical, Journal, Epigenetic controller: Butyrate and Class I Histone Deacetylase Inhibitors Promote Differentiation of Neonatal Porcine Islet Cells into Beta Cells. (Pubmed Central) - Dec 16, 2021
Our study revealed that butyrate treatment has the capacity to increase the number of beta cells, which may be predominantly mediated through its HDAC inhibitory activity. Butyrate and specific class I HDAC inhibitors may represent beneficial supplements to promote differentiation of neonatal porcine islet cells towards beta cells for cell replacement therapies.
- |||||||||| Jingzhuda (entinostat) / EOC Pharma, EddingPharm
Trial completion, Enrollment change, Trial completion date, Metastases: Drug-Drug Interaction Study of Entinostat and Exemestane in Postmenopausal Women With ER+ Breast Cancer (clinicaltrials.gov) - Dec 15, 2021
P1, N=61, Completed,
Butyrate and specific class I HDAC inhibitors may represent beneficial supplements to promote differentiation of neonatal porcine islet cells towards beta cells for cell replacement therapies. Active, not recruiting --> Completed | N=40 --> 61 | Trial completion date: Dec 2018 --> Jul 2021
- |||||||||| entinostat (SNDX-275) / Kyowa Kirin, Syndax Pharma
Journal: Entinostat Improves Motor Function and Neuronal Damage Via Downregulating NLRP3 Inflammasome Activation After Spinal Cord Injury. (Pubmed Central) - Dec 14, 2021
In summary, we first documented that entinostat improved the motor function, histopathologic damage, and local inflammatory response and NLRP3 inflammasome activation in the spinal cord following SCI and also presented the neuroprotective role of OGD-induced neuronal damage via the NLRP3 inflammasome. Thus, our study has the potential to reveal the interaction between the HDAC and NLRP3 inflammasome in the pathologic process as well as SCI and further promote the clinical indications of HDACi entinostat and clinical treatment for the inflammatory response after SCI.
- |||||||||| 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) - Dec 7, 2021
P1/2, N=70, Recruiting,
Thus, our study has the potential to reveal the interaction between the HDAC and NLRP3 inflammasome in the pathologic process as well as SCI and further promote the clinical indications of HDACi entinostat and clinical treatment for the inflammatory response after SCI. Suspended --> Recruiting
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