- |||||||||| quisinostat (JNJ 26481585) / ChemRar, Viriom, CPI-203 / Novartis
Journal, Gene therapy: Utilizing Epigenetic Regulators to improve HSC-based lentiviral gene therapy. (Pubmed Central) - Jun 25, 2024
Of note, we demonstrated that addition of Quisinostat improved LV transduction efficiency of HSCs and early progenitors. Our suggested culture conditions highlight the potential therapeutic effect of epigenetic regulators in hematopoietic stem cell biology and their clinical applications to advance HSC-based gene correction.
- |||||||||| quisinostat (JNJ 26481585) / ChemRar, Viriom
Journal, Epigenetic controller: A comprehensive characterization of the dehydrogenase-reductase DHRS2 and its involvement in histone deacetylase inhibition. (Pubmed Central) - Jun 5, 2024
Our suggested culture conditions highlight the potential therapeutic effect of epigenetic regulators in hematopoietic stem cell biology and their clinical applications to advance HSC-based gene correction. With the emphasis on urologic malignancies (testicular germ cell tumors, urothelial, prostate, and renal cell carcinoma), this study concluded that elevated DHRS2 levels are indicative of a successful HDACi treatment and, thereby offering a novel putative predictive biomarker.
- |||||||||| NOVEL EPIGENETIC BASED DIFFERENTIATION THERAPY FOR ACUTE MYELOID LEUKEMIA (Poster Area (Hall 7)) - May 15, 2024 - Abstract #EHA2024EHA_1020;
Both compounds showed a mechanism of action different from other DACi, which was mediated bythe acetylation of non-histone proteins related to the enhancer-promoter chromatin regulatory complex. Thesecompounds represent a novel and promising approach for a differentiation-based therapy for testing in AMLpatients.
- |||||||||| Zolinza (vorinostat) / Merck (MSD), Farydak (panobinostat) / Secura Bio, quisinostat (JNJ 26481585) / ChemRar, Viriom
Journal, Epigenetic controller: Central Nervous System Distributional Kinetics of Selected Histone Deacetylase Inhibitors. (Pubmed Central) - Apr 27, 2024
Employing techniques that minimize the post-sampling degradation in plasma, brain and spinal cord, accurate CNS distributional kinetic parameters for these potentially useful compounds were determined. A knowledge of CNS exposure (Kp,uu), time to peak, and duration can inform dosing strategies in preclinical and clinical trials in selected CNS tumors.
- |||||||||| quisinostat (JNJ 26481585) / ChemRar, Viriom
Journal, Myeloid-derived suppressor cells: ?Np63 regulates MDSC survival and metabolism in triple-negative breast cancer. (Pubmed Central) - Mar 21, 2024
In current studies, targeting ?Np63 with inducible CRISPR knockout and Histone deacetylase inhibitor Quisinostat showed that ?Np63 is important for tumor progression and metastasis in established tumors by promoting myeloid-derived suppressor cell (MDSC) survival through tumor necrosis factor alpha...We further demonstrated that targeting ?Np63 sensitizes chemotherapy. Overall, we showed that ?Np63 reprograms the MDSC-mediated immunosuppressive functions in TNBC, highlighting the benefit of targeting ?Np63 in chemotherapy-resistant TNBC.
- |||||||||| quisinostat (JNJ 26481585) / ChemRar, Viriom
Acute and long-term responses to treatment with the HDAC inhibitor quisinostat in preclinical models of glioblastoma (Section 24) - Mar 5, 2024 - Abstract #AACR2024AACR_5428;
Considering that GSCs have been shown to establish synaptic junctions with healthy neurons to evoke enhanced excitatory currents within glioma cells and contribute to treatment resistance, further investigation of this shift upon HDAC inhibition is crucial. Ongoing studies are aimed at evaluating the significance of these cellular and molecular changes resulting from quisinostat treatment and whether the quisinostat-induced cell fate changes can be exploited for future combination therapy for GBM.
- |||||||||| quisinostat (JNJ 26481585) / ChemRar, Viriom
Journal: Quisinostat is a brain-penetrant radiosensitizer in glioblastoma. (Pubmed Central) - Nov 22, 2023
The pharmacokinetic-pharmacodynamic-efficacy relationship was established by correlating free drug concentrations and evidence of target modulation in the brain with survival benefit. Together, these data provide a strong rationale for clinical development of quisinostat as a radiosensitizer for the treatment of GBM.
- |||||||||| quisinostat (JNJ 26481585) / ChemRar, Viriom
Acute and long-term responses to quisinostat treatment in PDX models of glioblastoma (Exhibit Hall A/B) - Nov 11, 2023 - Abstract #SNO2023SNO_752;
LC-MS/MS, qRT-PCR, immunoblotting and immunocytochemistry assays confirmed increase in oxidative stress and neuronal markers upon acute treatment in vitro. Cancer cells often express higher levels of reactive oxygen species compared to normal tissue, and oxidative stress is linked to greater survival and proliferation of cancer cells.
- |||||||||| Review, Journal: Current insights and molecular docking studies of HIV-1 reverse transcriptase inhibitors. (Pubmed Central) - Oct 11, 2023
This review addresses HIV-1 structure, replication cycle, reverse transcription, and HIV drug targets. This study focuses on NRTIs and NNRTIs, their binding sites, mechanisms of action, FDA-approved drugs and drugs in clinical trials, their resistance and adverse effects, their molecular docking studies, and highly active antiretroviral therapy (HAART).
- |||||||||| dasatinib / Generic mfg.
Trial completion, Enrollment change: Low Dose Dasatinib (50 mg Daily) as First-line Treatment for Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia (clinicaltrials.gov) - Sep 22, 2023
P2, N=56, Completed,
This study focuses on NRTIs and NNRTIs, their binding sites, mechanisms of action, FDA-approved drugs and drugs in clinical trials, their resistance and adverse effects, their molecular docking studies, and highly active antiretroviral therapy (HAART). Active, not recruiting --> Completed | N=100 --> 56
- |||||||||| quisinostat (JNJ 26481585) / ChemRar, Viriom, Istodax (romidepsin) / Astellas, BMS
Journal: Therapeutic HDAC inhibition in hypermutant diffuse intrinsic pontine glioma. (Pubmed Central) - Sep 1, 2023
Active, not recruiting --> Completed | N=100 --> 56 We screened PBT-24FH cells for sensitivity to a panel of HDAC inhibitors (HDACis) in vitro, identifying two HDACis associated with low nanomolar IC50s, quisinostat (27
- |||||||||| AV5080 / Viriom
Journal: Resistance profiles for the investigational neuraminidase inhibitor AV5080 in influenza a and B viruses. (Pubmed Central) - Aug 29, 2023
The resistance profiles and predicted binding modes of AV5080 and zanamivir are most similar, but dissimilar to those of oseltamivir, in part because of a guanidine moiety compensatory binding effect. Overall, our data suggests that AV5080 is a promising oral-dosed NAI that exhibited similar or superior in vitro efficacy against viruses with reduced or highly reduced inhibition phenotypes with respect to currently approved NAIs.
- |||||||||| AV5080 / Viriom, Relenza (zanamivir) / GSK, Vaxart, Xofluza (baloxavir marboxil) / Roche, Shionogi
Journal: Antiviral susceptibility of clade 2.3.4.4b highly pathogenic avian influenza A(H5N1) viruses isolated from birds and mammals in the United States, 2022. (Pubmed Central) - Aug 29, 2023
Of 1,015 sequences of HPAI A(H5N1) viruses collected in the United States during 2022, eight viruses (?0.8%) had a molecular marker of drug resistance to an FDA-approved antiviral: three adamantane-resistant (M2-V27A), four oseltamivir-resistant (NA-H275Y), and one baloxavir-resistant (PA-I38T)...Oseltamivir was least potent at inhibiting NA activity, while the investigational NA inhibitor AV5080 was most potent, including against NA mutants...Viruses with PA-I38M or PA-A37T showed 5- to 10-fold reduced susceptibilities. As HPAI A (H5N1) viruses continue to circulate and evolve, close monitoring of drug susceptibility is needed for risk assessment and to inform decisions regarding antiviral stockpiling.
- |||||||||| alvocidib (DSP-2033) / Sumitomo Pharma, quisinostat (JNJ 26481585) / ChemRar, Viriom, navitoclax (ABT 263) / AbbVie
Journal: Patient-derived zebrafish xenografts of uveal melanoma reveal ferroptosis as a drug target. (Pubmed Central) - Jun 16, 2023
Importantly, the ferroptosis-related genes GPX4 and SLC7A11 are negatively correlated with the survival of UM patients (TCGA: n?=?80; Leiden University Medical Centre cohort: n?=?64), ferroptosis susceptibility is correlated with loss of BAP1, one of the key prognosticators for metastatic UM, and ferroptosis induction greatly reduced metastasis formation in the UM xenograft model. Collectively, we have established a patient-derived animal model for metastatic UM and identified ferroptosis induction as a possible therapeutic strategy for the treatment of UM patients.
- |||||||||| quisinostat (JNJ 26481585) / ChemRar, Viriom, CPI-203 / MorphoSys
Small Molecule Epigenetic Modulators for Ex Vivo Expansion of Human Hematopoietic Stem Cells (Board No. 913) - Apr 21, 2023 - Abstract #ASGCT2023ASGCT_1486;
Both ex vivo and in vivo results suggest a positive role of CPI203 and Quisinostat on ex vivo expansion of HSCs and negative effect of IL3 during ex vivo culture of human cord blood HSCs. Clinical implementation of these findings is crucial to eventually boost HSC based gene- and cell-based therapies.
- |||||||||| Elpida (elsulfavirine) / Viriom
Thanks Elpida🥰 (Twitter) - Feb 9, 2023
- |||||||||| Elpida (elsulfavirine) / Viriom
Thanks Elpida (Twitter) - Jul 20, 2022
- |||||||||| Review, Journal: Approved HIV reverse transcriptase inhibitors in the past decade. (Pubmed Central) - Jul 20, 2022
Novel RT inhibitors such as islatravir, MK-8504, MK-8507, MK8583, IQP-0528, and MIV-150 will be also highlighted. Future development may focus on the new generation of novel antiretroviral inhibitors with higher bioavailability, longer elimination half-life, more favorable side-effect profiles, fewer drug-drug interactions, and higher activities against circulating drug-resistant strains.
- |||||||||| quisinostat (JNJ 26481585) / J&J, ChemRar
Exploiting genetic vulnerabilities of BAP1 loss by HDAC inhibitors (Poster Area) - Jun 28, 2022 - Abstract #EACR2022EACR_1226;
Besides, by treating cells with the HDAC inhibitor quisinostat, we detected a stronger decrease of cell viability of BAP1‑ deficient cell lines compared to wild-type BAP1 cell lines...Furthermore, in vivo studies in mice revealed a significant depletion of tumor growth after knockdown of the histone deacetylase in the context of BAP1 loss, strongly suggesting this HDAC as a true synthetic lethal interactor with BAP1 loss. Conclusion HDAC inhibitors might be effective for treating patients of renal cell carcinoma, uveal melanoma and/or cholangiocarcinoma with mutations in BAP1 .
- |||||||||| Elpida (elsulfavirine) / Viriom, depulfavirine (VM-1500A-LAI) / Viriom
Enrollment open, Trial completion date: Study of Single Ascending Doses of Elsulfavirine to Evaluate the Safety, Tolerability, and Pharmacokinetics of Elsulfavirine and Its Active Metabolite VM-1500A in Healthy Subjects (clinicaltrials.gov) - Apr 12, 2022
P1, N=24, Recruiting,
In summary, we discovered the promising candidate PfHDAC1 inhibitor JX35, which showed stronger triple-stage antimalarial effects and lower toxicity than quisinostat. Not yet recruiting --> Recruiting | Trial completion date: Mar 2022 --> Jun 2022
- |||||||||| quisinostat (JNJ 26481585) / J&J, ChemRar
Review, Journal: Repurposing Anticancer Drugs To Tackle Malaria. (Pubmed Central) - Feb 19, 2022
In this context, Huang & colleagues prioritized compounds that can block the activity of epigenetic enzymes, and described the discovery of a selective P. falciparum histone deacetylase (HDAC) inhibitor with high activity against various stages of the parasite. These findings may pave the way toward developing new lead compounds with broad-spectrum activity, thus facilitating malaria treatment and elimination.
- |||||||||| quisinostat (JNJ 26481585) / J&J, ChemRar
Polyphosphazenes as delivery systems for contrast agents and drugs (Room 6E (San Diego Convention Center)) - Jan 28, 2022 - Abstract #ACSSp2022ACS_Sp_11981;
We loaded this hydrogel with an anti-glioblastoma drug, quisinostat, and gold nanoparticles, which provide radiopacity and enhance the effects of radiotherapy. We found that this hydrogel effectively controlled tumors in a mouse model of glioblastoma, without side effects.
- |||||||||| Elpida (elsulfavirine) / Viriom
Trial completion, Enrollment change: Pharmacokinetics Study to Evaluate Drug-Drug Interactions and Safety of Elpida (clinicaltrials.gov) - Jan 26, 2022
P1, N=56, Completed,
Further, we extensively analyzed off-target effects and modes-of-action, which are important for risk assessment of the individual drugs. Not yet recruiting --> Completed | N=42 --> 56
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