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- | Journal: Impact of IL-15 and latency reversing agent combinations in the reactivation and NK cell-mediated suppression of the HIV reservoir. (Pubmed Central) - Nov 12, 2022
Finally, by using effectors (NK) and targets (latently infected CD4 T cells) equally exposed to drug combinations, we found that IL-15-mediated suppression of HIV reactivation by NK cells was inhibited by Panobinostat. Our data raise concerns and encouragements for therapeutic application of IL-15/LRA combinations.
- | Zolinza (vorinostat) / Merck (MSD), entinostat (SNDX-275) / Syndax Pharma, EOC Pharma
Journal, Epigenetic controller: Celastrol inhibits lung cancer growth by triggering histone acetylation and acting synergically with HDAC inhibitors. (Pubmed Central) - Nov 9, 2022
In addition to upregulating H4K16 acetylation (H4K16ac), celastrol regulates H3K4 tri-methylation and H3S10 phosphorylation. Celastrol treatment significantly enhanced the suppressive effects of HDACi on lung cancer cell allografts in mice, with significant H4K16ac upregulation, indicating that a combination of celastrol and HDACi is a potential novel therapeutic approach for patients with lung cancer.
- | Jingzhuda (entinostat) / EOC Pharma, EddingPharm, Opdivo (nivolumab) / BMS
Trial completion date, Trial primary completion date, Tumor mutational burden: INFORM2 NivEnt: INFORM2 Study Uses Nivolumab and Entinostat in Children and Adolescents With High-risk Refractory Malignancies (clinicaltrials.gov) - Nov 9, 2022
P1/2, N=128, Recruiting, Sponsor: University Hospital Heidelberg
Celastrol treatment significantly enhanced the suppressive effects of HDACi on lung cancer cell allografts in mice, with significant H4K16ac upregulation, indicating that a combination of celastrol and HDACi is a potential novel therapeutic approach for patients with lung cancer. Trial completion date: Mar 2023 --> Jun 2025 | Trial primary completion date: Sep 2022 --> Jun 2024
- || entinostat (SNDX-275) / Syndax Pharma, EOC Pharma
Review, Journal, Epigenetic controller: Synergistic association of resveratrol and histone deacetylase inhibitors as treatment in amyotrophic lateral sclerosis. (Pubmed Central) - Nov 8, 2022
The combination of the epigenetic drugs, by rescuing RelA and the H3 acetylation state, promotes a beneficial and sexually dimorphic effect on disease onset, survival and motor neurons degeneration. In this mini review, we discuss the potential of the epigenetic combination of resveratrol with HDAC inhibitors in the ALS treatment.
- ||| revumenib (SNDX-5613) / Syndax Pharma
https://t.co/38UtNgsXsp #ASH22 SNDX-5613 in RR leukemia showed ORR ~ 50%, CR/CRi ~ 30%, median DOR 9.1 months and median OS was 7 months. #leusm #ASH22 (Twitter) - Nov 7, 2022
- revumenib (SNDX-5613) / Syndax Pharma
Inhibition of the Menin-MLL1 Interaction in MLL-Rearranged Primary Mixed-Phenotype Acute Leukemia Samples Promotes Leukemic Differentiation (ENMCC - Hall D) - Nov 4, 2022 - Abstract #ASH2022ASH_5953;
Here we investigated potential application of the Menin-MLL inhibitor SNDX-5613 in MLL/AF4 MPAL infants who presented with the bilineage B/Myeloid phenotype...These myeloid data are consistent with observations of differentiation syndrome as an on-target effect in current clinical trials while the phenotypic changes in the lymphoid cells are new findings. Together, these data strongly suggests that MLL-r MPAL patients could benefit from the inclusion of the Menin-MLL1 inhibitors into their treatment regimens.
- Keytruda (pembrolizumab) / Merck (MSD), entinostat (SNDX-275) / Syndax Pharma, EOC Pharma
A Multi-Center Phase Ib Trial of the Histone Deactylase Inhibitor (HDACi) Entinostat in Combination with Anti-PD1 Antibody Pembrolizumab in Patients with Refractory/Relapsed Myelodysplastic Syndromes (RR-MDS) or Oligoblastic Acute Myeloid Leukemia (RR-AML) after Hypomethylating Agent (HMA) Failure (ENMCC - Hall D) - Nov 4, 2022 - Abstract #ASH2022ASH_5901;
P1b
In this multi-center phase 1b investigator-initiated trial in MDS and oligoblastic AML pts after HMA failure, entinostat + pembrolizumab at DL1 was reasonably tolerated but had limited therapeutic efficacy. Ongoing correlative work will explore the disconnect between the preclinical and clinical data regarding potential synergy of entinostat + pembrolizumab.
- Venclexta (venetoclax) / Roche, AbbVie, revumenib (SNDX-5613) / Syndax Pharma
A Phase 1b Dose Escalation and Expansion Study of SNDX-5613, Azacitidine (AZA) and Venetoclax (VEN) in Newly Diagnosed, Patients = 60 Years with Untreated NPM1-Mutated/ FLT3-Wild Type AML or KMT2A-Rearranged Acute Myeloid Leukemia (AML) (ENMCC - Hall D) - Nov 4, 2022 - Abstract #ASH2022ASH_5895;
P1/2
Additionally, the study will evaluate the impact of MRD, as measured by central flow cytometry and next-generation sequencing of NPM1 mutations. Additional evaluations and biomarkers of potential interest include menin- KMT2A-specific transcriptomic changes, myeloid differentiation/cell subset changes, mechanisms of resistance, and discovery of baseline features (methylation, mutations, etc.) that can impact outcomes.
- lanraplenib (GS-9876) / Gilead, Galapagos, Kronos Bio, entospletinib (GS-9973) / Kronos Bio
SYK Inhibitors, Entospletinib and Lanraplenib, Show Potent Anti-Leukemic Activity in Combination with Targeted Agents (ENMCC - Hall D) - Nov 4, 2022 - Abstract #ASH2022ASH_4064;
P1b/2, P3
Two highly selective SYK inhibitors are currently undergoing clinical testing in different but complementary clinical settings. Given its central role as a modulator of leukemogenic signaling, SYK inhibition has the potential to synergize with other targeted therapies in AML.
- Xpovio (selinexor) / Karyopharm, Menarini, FORUS Therap, VTP-50469 / Syndax Pharma
Mutant NPM1 Is Recruited to MLL Target Genes Via Its Acidic Stretch and Nuclear Export Factor CRM1 and Regulates Oncogenic Transcription in Acute Myeloid Leukemia (ENMCC - Hall D) - Nov 4, 2022 - Abstract #ASH2022ASH_4012;
Overall, we demonstrate that NPM1c chromatin binding is mediated by a combination of factors, including the CRM1-NES interaction, the acidic region of NPM1c, and the presence of the MLL complex. We further show that NPM1c acts in collaboration with the MLL1 complex to enhance oncogenic transcription and define the mechanism by which MLL1-Menin small molecule inhibitors produce clinical responses in patients with NPM1-mutated AML.
- Pharmacologic Inhibition of DYRK1A Results in Hyperactivation and Hyperphosphorylation of MYC and ERK Rendering KMT2A-R ALL Cells Sensitive to BCL2 Inhibition (ENMCC - Hall D) - Nov 4, 2022 - Abstract #ASH2022ASH_2364;
Targeting DYRK1A results in the accumulation of BIM, which renders the cells sensitive to BCL2 inhibition via venetoclax. While further in vivo studies are needed, we predict that combining DYRK1A inhibition with venetoclax may be a novel precision medicine strategy for the treatment of KMT2A-R ALL.
- ALLG AMLM26 Phase 1B/2 Study Investigating Novel Therapies to Target Early Relapse and Clonal Evolution As Pre-Emptive Therapy in AML (INTERCEPT): A Multi-Arm, Precision-Based, Recursive, Platform Trial (ENMCC - Hall D) - Nov 4, 2022 - Abstract #ASH2022ASH_2286;
Where no specific targeted treatment is available, patients will be randomly allocated to non-targeted therapies, if more than one applicable arm exists, to arms including sabatolimab, sabatolimab + azacitidine, ASTX727 + VEN or LDAC + VEN...Key secondary endpoints will be nadir MRD response, MRD clearance rate, median time to and duration of MRD response, relapse-free survival, overall survival and quality of life measures. Exploratory objectives will include analysis of drug resistance mechanisms and correlates of response.
- HDAC Inhibition Involves CD26 Induction on Multiple Myeloma Cells Via the c-Myc/Sp1-Mediated Prompter Activation and Overcomes Therapeutic Resistance By Humanized Antibody (ENMCC - Hall D) - Nov 4, 2022 - Abstract #ASH2022ASH_2199;
Although the cell surface expression of CD26 was relatively low or not detected on 5 MM cell lines (KMS26, KMS27, KMS28, KMS11, RPMI8226), cultured alone, the increased expression in CD26 levels of MM cells was detectable within 24 hr of the treatment with HDAC1i; FK228, HDAC3i; BG45, MS-275, RG2833 or HDAC6i; nexturastat A, tubastatin A, ACY-1215 as well as broad HDACi; LBH-589, SAHA by flow cytometry... HDACi not only shows anti-MM activity itself but sensitizes MM cells with CD26 antigen loss to CD26mAb via c-Myc/Sp1-mediated CD26 induction and augments its cytotoxicity.
- revumenib (SNDX-5613) / Syndax Pharma
Outcomes after Transplant in Relapsed/Refractory KMT2Ar (MLLr) and mNPM1 (NPM1c) leukemia Patients Achieving Remissions after Menin Inhibition: SNDX-5613 (revumenib) Ph1 Experience (ENMCC - 353-355) - Nov 4, 2022 - Abstract #ASH2022ASH_1798;
P1/2
In addition to patients achieving CR/CRh, two patients with CRp also had ongoing remissions post-transplant. AUGMENT-101 continues to enroll patients, agnostic of transplant eligibility, with the option for SNDX-5613 post-transplant maintenance.
- Jakafi (ruxolitinib) / Novartis, Incyte, entinostat (SNDX-275) / Syndax Pharma, EOC Pharma
The High Mobility Group A1 Chromatin Regulator Drives Immune Evasion during MPN Progression By Repressing Genes Involved in Antigen Presentation (ENMCC - 275-277) - Nov 4, 2022 - Abstract #ASH2022ASH_1750;
Most importantly, HMGA1 immune evasion networks are dysregulated in human MPN after progression to AML. Together, our studies reveal a new paradigm whereby HMGA1 down-regulates MHC antigens during MPN progression, suggesting that targeting HMGA1 networks with entinostat could activate an immune attack and prevent MPN progression.
- Beleodaq (belinostat) / Aurobindo, entinostat (SNDX-275) / Syndax Pharma, EOC Pharma
Orthogonal Proteogenomic Approaches Identify the Druggable PA2G4-MYC Axis in 3q26 AML (ENMCC - 353-355) - Nov 4, 2022 - Abstract #ASH2022ASH_1675;
We focused on the compounds with pan (AR-42, belinostat) or selective (entinostat) HDAC inhibitory properties...We translated these results in a “N-of-1” clinical trial proposing entinostat in association with azacytidine to patients with relapse/refractory 3q26 AML based on a compassionate use program for this regimen...This effect was not observed in patients treated with cytarabine...These data support the evidence that PA2G4 is a mediator of Evi1-Myc axis in AML. In conclusion, our work positions PA2G4 at the crosstalk of the Evi1-Myc leukemogenic signal for developing new therapeutics and, at this interesting time, urges upfront HDACi-based combination therapies in patients with 3q26 AML.
- revumenib (SNDX-5613) / Syndax Pharma
The Menin Inhibitor SNDX-5613 (revumenib) Leads to Durable Responses in Patients (Pts) with KMT2A-Rearranged or NPM1 Mutant AML: Updated Results of a Phase (Ph) 1 Study (ENMCC - 220-222) - Nov 4, 2022 - Abstract #ASH2022ASH_1357;
Treatment was well-tolerated, associated with a low frequency of =grade 3 TRAEs and durable remissions in pts with leukemia refractory to multiple prior lines of therapy. Enrollment on Ph 2 of AUGMENT-101 is ongoing.
- VTP-50469 / Syndax Pharma
Epigenetic Resistance to Menin-MLL1 Inhibition Is Driven By Loss of the Non-Canonical Polycomb Repressive Complex 1.1 in NUP98-Rearranged AML (ENMCC - 343-345) - Nov 4, 2022 - Abstract #ASH2022ASH_1334;
Menin-MLL1 inhibition using a small molecule VTP50469 simultaneously represses pro-leukemogenic genes and upregulates markers of myeloid differentiation...In summary, these results demonstrate that the NUP98-fusion-Menin-MLL complex and PRC1.1 dynamically compete for transcriptional control of developmentally regulated, stem-cell associated genes. Loss of PRC1.1 may promote NUP98-fusion protein-driven leukemogenesis and mediates resistance to Menin-MLL1 inhibition by failing to epigenetically silence genes that are essential for maintaining an undifferentiated, stem cell-like state.
- Avastin (bevacizumab) / Roche, Jingzhuda (entinostat) / EOC Pharma, EddingPharm, Tecentriq (atezolizumab) / Roche
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) - Nov 1, 2022
P1/2, N=72, Suspended, Sponsor: Roberto Pili
Loss of PRC1.1 may promote NUP98-fusion protein-driven leukemogenesis and mediates resistance to Menin-MLL1 inhibition by failing to epigenetically silence genes that are essential for maintaining an undifferentiated, stem cell-like state. Trial completion date: Dec 2023 --> Jun 2024 | Trial primary completion date: Dec 2022 --> Jun 2023
- || Jingzhuda (entinostat) / EOC Pharma, EddingPharm
Trial completion, Enrollment change, Trial completion date: Breast 49: A Pilot Study of the Combination of Entinostat With Capecitabine in High Risk Breast Cancer After Neo-adjuvant Therapy (clinicaltrials.gov) - Nov 1, 2022
P1, N=13, Completed, Sponsor: University of Virginia
Trial completion date: Dec 2023 --> Jun 2024 | Trial primary completion date: Dec 2022 --> Jun 2023 Recruiting --> Completed | N=55 --> 13 | Trial completion date: Oct 2028 --> Nov 2022
- ||| axatilimab (SNDX-6352) / Syndax Pharma, Incyte
Enrollment closed, Trial completion date, Trial primary completion date: AGAVE-201: A Study of Axatilimab at 3 Different Doses in Participants With Chronic Graft Versus Host Disease (cGVHD) (clinicaltrials.gov) - Oct 31, 2022
P2, N=241, Active, not recruiting, Sponsor: Syndax Pharmaceuticals
Recruiting --> Completed | N=55 --> 13 | Trial completion date: Oct 2028 --> Nov 2022 Recruiting --> Active, not recruiting | Trial completion date: Jul 2023 --> Dec 2023 | Trial primary completion date: Jul 2023 --> Dec 2023
- | entinostat (SNDX-275) / Syndax Pharma, EOC Pharma, Istodax (romidepsin) / Astellas, BMS
Preclinical, Journal, Epigenetic controller: Histone Deacetylase Inhibition Restores Behavioral and Synaptic Function in a Mouse Model of 16p11.2 Deletion. (Pubmed Central) - Oct 27, 2022
Recruiting --> Active, not recruiting | Trial completion date: Jul 2023 --> Dec 2023 | Trial primary completion date: Jul 2023 --> Dec 2023 Our results suggest that HDAC inhibition provides a highly effective therapeutic strategy for behavioral deficits and excitation/inhibition imbalance in 16p11del/+ mice, likely via normalization of synaptic function in the PFC.
- | entinostat (SNDX-275) / Syndax Pharma, EOC Pharma
Journal: Neurotrophin3 promotes hepatocellular carcinoma apoptosis through the JNK and P38 MAPK pathways. (Pubmed Central) - Oct 21, 2022
These results indicate that NTF3 is a tumor suppressor, and that its low expression can help in predict poor clinical outcomes in HCC. Therefore, NTF3 can be used as a potential treatment molecule for HCC.
- || Venclexta (venetoclax) / Roche, AbbVie, revumenib (SNDX-5613) / Syndax Pharma, Inqovi (decitabine/cedazuridine) / Otsuka
Enrollment open: A Phase I-II Study Investigating the All Oral Combination of the Menin Inhibitor SNDX-5613 With Decitabine/Cedazuridine (ASTX727) and Venetoclax in Acute Myeloid Leukemia (SAVE) (clinicaltrials.gov) - Oct 18, 2022
P1/2, N=43, Recruiting, Sponsor: M.D. Anderson Cancer Center
Therefore, NTF3 can be used as a potential treatment molecule for HCC. Not yet recruiting --> Recruiting
- entinostat (SNDX-275) / Syndax Pharma, EOC Pharma
Histone Deacetylase Inhibitors Enhance the Urinary Tract's Immune Response in Diabetic Mice (Exhibit Hall, Orange County Convention Center, West Building) - Oct 13, 2022 - Abstract #KIDNEYWEEK2022KIDNEY_WEEK_2109;
By increasing bladder barrier strength and AMP production using MS-275, the kidneys may be shielded from the deleterious effects of DM and UTI. Further studies are needed to assess the effectiveness of using MS-275 in individuals with DM to reduce UTI susceptibility and protect the kidneys.
- entinostat (SNDX-275) / Syndax Pharma, EOC Pharma
Association of muscle mass and density with outcomes in patients with ER positive metastatic breast cancer: correlative analysis of ECOG-ACRIN 2112 (Hall 1) - Oct 10, 2022 - Abstract #SABCS2022SABCS_852;
Muscle measures correlated with obesity and performance status; however, neither low SMI nor low SMA were associated with worse prognosis in this population. Further work is needed to refine body composition measurements and select optimal cutoffs and meaningful endpoints in specific breast cancer populations, particularly in those living with metastatic disease.
- | Jingzhuda (entinostat) / EOC Pharma, EddingPharm
Enrollment change, Trial termination: Entinostat Neuroendocrine (NE) Tumor (clinicaltrials.gov) - Oct 7, 2022
P2, N=5, Terminated, Sponsor: Antonio Fojo
Further work is needed to refine body composition measurements and select optimal cutoffs and meaningful endpoints in specific breast cancer populations, particularly in those living with metastatic disease. N=40 --> 5 | Recruiting --> Terminated; Lack of funding and drug supply
- guadecitabine (SGI-110) / Otsuka, entinostat (SNDX-275) / Syndax Pharma, EOC Pharma
Epigenetic modifications influence immune regulatory pathways in murine and human neuroblastoma and melanoma tumor models (Hall C) - Oct 6, 2022 - Abstract #SITC2022SITC_1421;
By combining guadecitabine and entinostat with current immunotherapeutic regimens, there is potential to reinvigorate the activity of T cells in the anti-tumor response through T cell engagement with MHCI/II. Future studies are aimed to investigate the in vivo ability of guadecitabine and entinostat to restore MHCI/II expression.
- Keytruda (pembrolizumab) / Merck (MSD), entinostat (SNDX-275) / Syndax Pharma, EOC Pharma
Acquired resistance to immune checkpoint blockade by phenotypic plasticity of melanoma (Hall C) - Oct 6, 2022 - Abstract #SITC2022SITC_1227;
Ethics Approval The work described herein was approved by the Dana Farber Harvard Cancer Center IRB, protocol #11-181, to which the patient signed informed consent. Consent The work described herein was approved by the Dana Farber Harvard Cancer Center IRB, protocol #11-181, to which the patient signed informed consent.
- bintrafusp alfa (M7824) / EMD Serono, M-9241 / EMD Serono, entinostat (SNDX-275) / Syndax Pharma, EOC Pharma
Phase I/II Evaluation of the Combination of Entinostat, M9241 and Bintrafusp Alfa in Patients with Advanced HPV Related Malignancies (Hall C) - Oct 6, 2022 - Abstract #SITC2022SITC_1081;
P1/2
To date the triple combination appears to have a manageable safety profile along with encouraging clinical activity in patients with advanced checkpoint refractory HPV related cancers including in pts who have previously progressed on PD(L)1 inhibitor then on PDS0101, M9241 and bintrafusp alfa. Trial Registration NCT04708470
- | entinostat (SNDX-275) / Syndax Pharma, EOC Pharma
Biomarker, Journal, Tumor microenvironment: HDACi promotes inflammatory remodeling of the tumor microenvironment to enhance epitope spreading and antitumor immunity. (Pubmed Central) - Oct 5, 2022
Importantly, MS-275 alters the immunodominance hierarchy by directing epitope spreading towards endogenous retroviral tumor-associated antigen, p15E. Our data suggest that MS-275 multi-mechanistically improves epitope spreading to promote long-term clearance of solid tumors.
- || revumenib (SNDX-5613) / Syndax Pharma
Enrollment open: Study of Radiolabeled Revumenib in Adults With Acute Leukemia (clinicaltrials.gov) - Oct 5, 2022
P1, N=8, Recruiting, Sponsor: Syndax Pharmaceuticals
Our data suggest that MS-275 multi-mechanistically improves epitope spreading to promote long-term clearance of solid tumors. Not yet recruiting --> Recruiting
- entinostat (SNDX-275) / Syndax Pharma, EOC Pharma
Histone deacetylase inhibitor therapy boosts RNase 4 and 7 expression and protects against invasive uropathogenic E. coli infection. (Glen 201-204) - Sep 20, 2022 - Abstract #IPNA2022IPNA_58;
We identified the class I HDACi, MS275 (entinostat), as a selective and potent AMP inducer...These findings show that HDACi boost RNase 4 and 7 expression and reduce UTI susceptibility. Identification of strategies to enhance host AMP expression represents a paradigm shift away from conventionally used antibiotics as UTI therapies.
- | entinostat (SNDX-275) / Syndax Pharma, EOC Pharma
Journal, Epigenetic controller: Inhibition of Class I Histone Deacetylase Activity Blocks the Induction of TNFAIP3 Both Directly and Indirectly via the Suppression of Endogenous TNF-α. (Pubmed Central) - Sep 18, 2022
In addition to TNFAIP3, TNF-α is known to induce many response genes that orchestrate the inflammatory cascade. Thus, suppression of TNF-α may represent a general mechanism through which HDIs regulate a selected set of target genes.
- | entinostat (SNDX-275) / Syndax Pharma, EOC Pharma
Preclinical, Journal: In Vivo Two-Photon Imaging Analysis of Dynamic Degradation of Hepatic Lipid Droplets in MS-275-Treated Mouse Liver. (Pubmed Central) - Sep 18, 2022
In addition, MS-275 reduced the de novo lipogenesis, but increased the mitochondrial oxidation and the expression levels of oxidation-related genes, such as PPARa, MCAD, CPT1b, and FGF21. Taken together, these results suggest that MS-275 stimulates the degradation of hepatic LDs and mitochondrial free fatty acid oxidation, thus protecting against HFD-induced NAFLD.
- |||||| axatilimab (SNDX-6352) / Syndax Pharma, Incyte
New trial: Expanded Access of Axatilimab to Treat a Single Patient With Chronic Graft Versus Host Disease (clinicaltrials.gov) - Sep 16, 2022
P=N/A, N=0, Available, Sponsor: Incyte Corporation
- | entinostat (SNDX-275) / Syndax Pharma, EOC Pharma
Journal: Repression of enhancer RNA PHLDA1 promotes tumorigenesis and progression of Ewing sarcoma via decreasing infiltrating T-lymphocytes: A bioinformatic analysis. (Pubmed Central) - Sep 14, 2022
Connectivity Map Analysis screened two candidate compounds, MS-275 and pyrvinium, that might target Ewing sarcoma...PHLDA1 is directly repressed by EWS/FLI1 protein and low expression of FOSL2, resulting in the deregulation of FOX proteins and CC chemokine receptors. The decrease of infiltrating T-lymphocytes and TNFA signaling may promote tumorigenesis and progression of Ewing sarcoma.
- | entinostat (SNDX-275) / Syndax Pharma, EOC Pharma
Journal: Dynamic Expression of EpCAM in Primary and Metastatic Lung Cancer Is Controlled by Both Genetic and Epigenetic Mechanisms. (Pubmed Central) - Sep 13, 2022
Moreover, tumor-associated macrophages (TAMs) impede EpCAM expression probably through TGFβ-induced EMT signaling. These findings unveil the dynamic expression patterns of EpCAM and differential roles of epigenetic modification in EpCAM expression in primary and metastatic lung tumors, providing novel insights into tumor cell isolation and lung cancer diagnosis.
- | Journal, PARP Biomarker: Construction of a prognostic model related to copper dependence in breast cancer by single-cell sequencing analysis. (Pubmed Central) - Sep 13, 2022
Veliparib, Selumetinib, Entinostat, and Palbociclib were found to be more sensitive medications for the high-risk group after drug sensitivity analysis. Our CDRG-based prognostic model can aid in the prediction of prognosis and treatment of BC patients.
- || entinostat (SNDX-275) / Syndax Pharma, EOC Pharma, Stivarga (regorafenib) / Bayer
P1 data, Journal: Phase I Trial of Regorafenib, Hydroxychloroquine, and Entinostat in Metastatic Colorectal Cancer. (Pubmed Central) - Sep 10, 2022
P1/2
Our CDRG-based prognostic model can aid in the prediction of prognosis and treatment of BC patients. The combination of regorafenib, HCQ, and entinostat was poorly tolerated without evident activity in metastatic CRC.
- | Farydak (panobinostat) / Secura Bio, Istodax (romidepsin) / Astellas, BMS
Preclinical, Journal: HDAC inhibitors Panobinostat and Romidepsin enhance tax transcription in HTLV-1-infected cell lines and freshly isolated patients' T-cells. (Pubmed Central) - Sep 10, 2022
In conclusion, these data demonstrate the ability of Panobinostat and Romidepsin to manipulate Tax expression and provide a foundation for further research into eliminating latently infected cells. These findings also contribute to a better understanding of conditions limiting transcription and translation of viral gene products.
- ||| axatilamab (SNDX-6352) / Syndax Pharma, Incyte
📹 Catch up! The #GvHD Hub was pleased to speak to @ckitko, @VUMChealth. We asked, Is axatilimab for cGvHD well tolerated and what does the preliminary response data look like ❓ This presentation, given by @StephanieLeeMD, was awarded Best of #ASH21 🏆 https://t.co/qHDdWNheqK (Twitter) - Sep 9, 2022
- | entinostat (SNDX-275) / Syndax Pharma, EOC Pharma
Journal, Epigenetic controller: β-Hydroxybutyrate upregulates FGF21 expression through inhibition of histone deacetylases in hepatocytes. (Pubmed Central) - Sep 3, 2022
HDACs' inhibition by entinostat upregulated FGF21 expression and eliminated β-OHB-stimulated FGF21 expression in HepG2 cells...Meanwhile, hepatic FGF21 expression and serum FGF21 levels were significantly increased in β-OHB-treated mice compared with the control. It is suggested that β-OHB upregulates FGF21 expression through inhibition of HDACs' activity in hepatocytes.
- ||| Jingzhuda (entinostat) / EOC Pharma, EddingPharm
Trial completion, Metastases: Study of Avelumab With or Without Entinostat in Participants With Advanced Epithelial Ovarian Cancer (clinicaltrials.gov) - Aug 22, 2022
P1b/2, N=140, Completed, Sponsor: Syndax Pharmaceuticals
It is suggested that β-OHB upregulates FGF21 expression through inhibition of HDACs' activity in hepatocytes. Unknown status --> Completed
- | Zolinza (vorinostat) / Merck (MSD), entinostat (SNDX-275) / Syndax Pharma
Journal, PARP Biomarker, Epigenetic controller: Quantitative Acetylomics Uncover Acetylation-Mediated Pathway Changes Following Histone Deacetylase Inhibition in Anaplastic Large Cell Lymphoma. (Pubmed Central) - Aug 22, 2022
This included acetylation of H2AX, PARP1 and previously unrecognized acetylation sites in TP53BP1. Our data provide a comprehensive view of the targets of HDAC inhibition in malignant T cells with general applicability and could have translational impact for the treatment of ALCL with HDACis alone or in combination therapies.
- | mocetinostat (MGCD0103) / Mirati, Otsuka, Epidaza (chidamide) / Chipscreen, Meiji Seika, Eisai, HUYA Bioscience, entinostat (SNDX-275) / Syndax Pharma
Journal: Large-Scale Identification of Multiple Classes of Host Defense Peptide-Inducing Compounds for Antimicrobial Therapy. (Pubmed Central) - Aug 22, 2022
Importantly, mocetinostat was more efficient than entinostat and tucidinostat, two structural analogs, in promoting HDP gene expression and the antibacterial activity of chicken macrophages. Taken together, mocetinostat, with its ability to enhance HDP synthesis and the antibacterial activity of host cells, could be potentially developed as a novel antimicrobial for disease control and prevention.
- | axatilimab (SNDX-6352) / Syndax Pharma, Incyte
Trial completion date, Trial primary completion date: SNDX-6352-0503: A Phase 1/2 Study to Evaluate SNDX- 6352 in Participants With Active cGVHD (clinicaltrials.gov) - Aug 19, 2022
P1/2, N=40, Active, not recruiting, Sponsor: Syndax Pharmaceuticals
Taken together, mocetinostat, with its ability to enhance HDP synthesis and the antibacterial activity of host cells, could be potentially developed as a novel antimicrobial for disease control and prevention. Trial completion date: Aug 2022 --> Feb 2023 | Trial primary completion date: Nov 2021 --> Aug 2022
- | Zolinza (vorinostat) / Merck (MSD), Farydak (panobinostat) / Secura Bio, entinostat (SNDX-275) / Syndax Pharma
Journal: Short chain fatty acids exhibit selective estrogen receptor downregulator (SERD) activity in breast cancer. (Pubmed Central) - Aug 16, 2022
Although acetate induced ERα degradation the mechanisms may be independent of the HDAC inhibitory activity of this compound. These results suggest that high fibre diets that induce formation of SCFAs may have some clinical efficacy for treating ER-positive endocrine resistant breast cancer patients and this is currently being investigated.
- entinostat (SNDX-275) / Kyowa Kirin, Syndax Pharma
ADAR1-dsRNA metabolism in myeloma cells with 1q amplification: a novel therapeutic target () - Aug 13, 2022 - Abstract #IMW2022IMW_342;
dsRNA overloading with ADAR1 inhibition may become a unique strategy targeting MM cells with Amp1q. Further study is warranted on the roles of ADAR1 for dsRNAediting and development of novel immunotherapies targeting dsRNA accumulation in high-risk MM.