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  • ||||||||||  RGFP966 / BioMarin, entinostat (SNDX-275) / Kyowa Kirin, Syndax Pharma, quisinostat (JNJ 26481585) / J&J, ChemRar
    Journal:  CaMKII exacerbates heart failure progression by activating class I HDACs. (Pubmed Central) -  Oct 9, 2021   
    CaMKII activates class I HDACs in heart failure, which may be a central mechanism for heart failure progression. Selective class I HDACs inhibition may be a novel therapeutic avenue to alleviate CaMKII hyperactivity induced cardiac dysfunction.
  • ||||||||||  Jingzhuda (entinostat) / EOC Pharma, EddingPharm
    Trial completion, Trial completion date:  Entinostat in Treating Pediatric Patients With Recurrent or Refractory Solid Tumors (clinicaltrials.gov) -  Oct 7, 2021   
    P1,  N=21, Completed, 
    Selective class I HDACs inhibition may be a novel therapeutic avenue to alleviate CaMKII hyperactivity induced cardiac dysfunction. Active, not recruiting --> Completed | Trial completion date: Aug 2022 --> Sep 2021
  • ||||||||||  Jingzhuda (entinostat) / EOC Pharma, EddingPharm
    Trial completion date, Trial primary completion date:  Entinostat Neuroendocrine (NE) Tumor (clinicaltrials.gov) -  Oct 7, 2021   
    P2,  N=40, Recruiting, 
    Active, not recruiting --> Completed | Trial completion date: Aug 2022 --> Sep 2021 Trial completion date: Aug 2021 --> Dec 2021 | Trial primary completion date: Aug 2019 --> Dec 2021
  • ||||||||||  Inlyta (axitinib) / Pfizer
    Journal, PD(L)-1 Biomarker, IO biomarker:  Axitinib and HDAC Inhibitors Interact to Kill Sarcoma Cells. (Pubmed Central) -  Oct 5, 2021   
    In vivo, axitinib and the HDAC inhibitor entinostat interacted to significantly reduce tumor growth. Collectively our findings support the exploration of axitinib and HDAC inhibitors being developed as a novel sarcoma therapy.
  • ||||||||||  Keytruda (pembrolizumab) / Merck (MSD), entinostat (SNDX-275) / Kyowa Kirin, Syndax Pharma
    Clinical, P2 data, Clinical Trial,Phase II, Journal:  The PEMDAC phase 2 study of pembrolizumab and entinostat in patients with metastatic uveal melanoma. (Pubmed Central) -  Oct 3, 2021   
    P2
    In conclusion, HDAC inhibition and anti-PD1 immunotherapy results in durable responses in a subset of patients with metastatic UM.Trial registration ClinicalTrials.gov registration number: NCT02697630 (registered 3 March 2016). EudraCT registration number: 2016-002114-50.
  • ||||||||||  entinostat (SNDX-275) / Kyowa Kirin, Syndax Pharma, saracatinib (AZD0530) / AstraZeneca
    Journal:  Prediction and identification of synergistic compound combinations against pancreatic cancer cells. (Pubmed Central) -  Sep 30, 2021   
    Examples of highly synergistic in vitro validated compound pairs include gemcitabine combined with Entinostat, thioridazine, loperamide, scriptaid and Saracatinib. Hence, the computational approach presented here was able to identify synergistic compound combinations against pancreatic cancer cells.
  • ||||||||||  entinostat (SNDX-275) / Kyowa Kirin, Syndax Pharma
    Preclinical, Journal:  Neuroprotective epi-drugs quench the inflammatory response and microglial/macrophage activation in a mouse model of permanent brain ischemia. (Pubmed Central) -  Sep 29, 2021   
    Our findings indicate that single treatment with MS-275 and resveratrol can reduce stroke-mediated brain injury and inflammation observed 2 days after the pMCAO and put the rational to test repeated administration of the drugs. The anti-inflammatory property of MS-275 and resveratrol combination can be ascribed to both primary direct inhibition of microglia/macrophage activation and secondary glial/macrophages inhibition mediated by neuroprotection.
  • ||||||||||  entinostat (SNDX-275) / Kyowa Kirin, Syndax Pharma
    Journal, Epigenetic controller:  Targeting foam cell formation in inflammatory brain diseases by the histone modifier MS-275. (Pubmed Central) -  Sep 26, 2021   
    The anti-inflammatory property of MS-275 and resveratrol combination can be ascribed to both primary direct inhibition of microglia/macrophage activation and secondary glial/macrophages inhibition mediated by neuroprotection. These findings identify class I-HDAC inhibition as a potential novel strategy to prevent disease promoting foam cell formation in CNS inflammation.
  • ||||||||||  doxorubicin hydrochloride / Generic mfg.
    Journal:  The protective effect of beta-hydroxybutyric acid on renal glomerular epithelial cells in adriamycin-induced injury. (Pubmed Central) -  Sep 21, 2021   
    In contrast, anacardic acid, a selective inhibitor of acetyltransferase, decreases the acetylation of nephrin, WT-1, and GSK3β and mitigates the podocyte protective effects of BHB. Taken together, BHB attenuates adriamycin-elicited glomerular epithelial cell injury, at least in part, by inhibiting the deacetylation of the key molecules implicated in glomerular injury.
  • ||||||||||  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.
  • ||||||||||  Jingzhuda (entinostat) / EOC Pharma, EddingPharm
    Enrollment change, Trial primary completion date:  Entinostat in Treating Pediatric Patients With Recurrent or Refractory Solid Tumors (clinicaltrials.gov) -  Aug 19, 2021   
    P1,  N=21, Active, not recruiting, 
    We propose that these drugs can be repurposed for COVID-19. N=36 --> 21 | Trial primary completion date: Jun 2022 --> Jun 2021
  • ||||||||||  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.
  • ||||||||||  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.