Duvyzat (givinostat)
Research Synopsis
Duvyzat (givinostat)
Apoptosis on hepatoma cells but not on primary hepatocytes by histone deacetylase inhibitors valproate and ITF2357.
London, UK
2 hours ago
1 Received
- Hepatocellular carcinoma (HCC) is hard to treat due to resistance to traditional chemotherapy, but histone deacetylase inhibitors (HDAC-Is) like valproate (VPA) and ITF2357 show potential for slowing down tumor growth and promoting cell death.
- In lab tests, VPA and ITF2357 effectively damaged HCC cells while being well-tolerated by healthy human liver cells, indicating selective efficacy against tumors.
- The study found key mechanisms of cell death involve changes in proteins that regulate apoptosis, suggesting that these HDAC-Is could be valuable new treatments for HCC without harming healthy cells.
$100 - $150
Hourly Rate
HDAC inhibitor treatment of hepatoma cells induces both TRAIL-independent apoptosis and restoration of sensitivity to TRAIL.
London, UK
2 hours ago
1 Received
- Hepatocellular carcinoma (HCC) is resistant to traditional chemotherapy and TRAIL, a treatment that induces cell death, but recent studies show that two histone deacetylase inhibitors (HDAC-I), valproic acid and ITF2357, can effectively target HCC cells.
- Unlike TRAIL-sensitive cells, HCC cells exhibit a mechanism of HDAC-I-induced apoptosis that doesn't rely on TRAIL or death receptor upregulation.
- Combining HDAC-I with TRAIL enhances cell death in HCC by reducing the levels of the FLICE inhibitory protein (FLIP), making this approach a promising and specific treatment for advanced HCC without harming healthy liver cells.
$100 - $150
Hourly Rate
The histone deacetylase inhibitor ITF2357 has anti-leukemic activity in vitro and in vivo and inhibits IL-6 and VEGF production by stromal cells.
London, UK
2 hours ago
1 Received
- - ITF2357 is a new drug that inhibits histone deacetylase and has shown to induce cell death (apoptosis) in numerous multiple myeloma and acute myelogenous leukemia cell lines, with strong efficacy at low concentrations.
- - The drug works by activating the intrinsic apoptotic pathway and altering levels of specific proteins, leading to increased acetylation of histones and tubulin, which may enhance its anti-cancer effects.
- - In animal studies, ITF2357 not only increased survival rates in mice with leukemia but also notably reduced the production of growth factors like IL-6 and VEGF from surrounding stromal cells, suggesting it could hinder tumor support systems.
$100 - $150
Hourly Rate
Histone deacetylase inhibitors induce in human hepatoma HepG2 cells acetylation of p53 and histones in correlation with apoptotic effects.
London, UK
2 hours ago
1 Received
- HDAC inhibitors (HDACIs) like Trichostatin A, ITF2357, and SAHA trigger cell death (apoptosis) in HepG2 liver cancer cells in a way that depends on the dose and duration of treatment.
- These inhibitors enhance acetylation of proteins such as p53 and histones fairly quickly, with significant effects observed as soon as 30 minutes after treatment.
- The study indicates that acetylated p53, alongside acetylated histones and coactivators, is crucial for the apoptosis induced by HDACIs in HepG2 cells.
$100 - $150
Hourly Rate
Selective anti-leukaemic activity of low-dose histone deacetylase inhibitor ITF2357 on AML1/ETO-positive cells.
London, UK
2 hours ago
1 Received
- The study investigated the effects of a new compound, ITF2357, on acute myeloid leukemia (AML) cells, highlighting its ability to induce histone acetylation and block cell proliferation.
- ITF2357 was particularly effective at a low concentration (0.1 microM) in killing AML1/ETO-positive Kasumi-1 cells and inducing apoptosis in other related cell lines when used at higher concentrations (1 microM).
- The findings suggest that ITF2357 not only promotes the degradation of the AML1/ETO fusion protein but also alters the localization of DNMT1 and p300 in the nucleus, indicating its potential as a targeted treatment for AML subtypes that express this fusion protein.
$100 - $150
Hourly Rate
The potential of histone deacetylase inhibitors for the treatment of multiple myeloma.
London, UK
2 hours ago
1 Received
- - Preclinical research indicates that histone deacetylase inhibitors have potential benefits for treating myeloma.
- - Initial studies show promising clinical effects of these inhibitors in myeloma patients.
- - Future research should focus on exploring combination treatment strategies to enhance effectiveness.
$100 - $150
Hourly Rate
The histone deacetylase inhibitor ITF2357 selectively targets cells bearing mutated JAK2(V617F).
London, UK
2 hours ago
1 Received
- ITF2357 is a new histone deacetylase inhibitor (HDACi) that shows promising antitumor effects specifically on cells with the JAK2(V617F) mutation found in patients with polycythemia vera and essential thrombocythemia.
- The compound significantly inhibits the clonogenic activity of mutated cells at very low concentrations (IC(50) 0.001-0.01 microM), promoting the growth of unmutated over mutated colonies by a factor of seven.
- ITF2357 effectively reduces both the JAK2(V617F) protein and its signaling pathways without affecting the wild-type JAK2 or other STAT proteins in healthy control cells, highlighting its targeted action against
$100 - $150
Hourly Rate
Histone deacetylases: novel targets for prevention of colitis-associated cancer in mice.
London, UK
2 hours ago
1 Received
- Inhibition of histone deacetylases (HDACs) shows potential for reducing inflammation and tumor growth in colon cancer models, particularly in the context of inflammatory bowel disease.
- The novel HDAC inhibitor ITF2357 was found to be more effective than suberoylanilide hydroxamic acid in improving inflammation and suppressing tumor growth in experimental colitis and cancer models.
- The mechanism of action involves increased acetylation of histones, reduced production of interferon gamma, enhanced apoptosis in immune cells, and inhibition of the NF-kappaB pathway.
$100 - $150
Hourly Rate
Histone deacetylase inhibition modulates indoleamine 2,3-dioxygenase-dependent DC functions and regulates experimental graft-versus-host disease in mice.
London, UK
2 hours ago
1 Received
- * These inhibitors significantly decrease the secretion of inflammatory cytokines and the expression of key co-stimulatory molecules on dendritic cells (DCs), which reduces their ability to stimulate T cell responses.
- * The research indicates that HDAC inhibitors boost the expression of indoleamine 2,3-dioxygenase (IDO), which inhibits DC function, and that blocking IDO reverses the immune suppression caused by these inhibitors, highlighting their potential in treating conditions related to immune response.
$100 - $150
Hourly Rate
The histone deacetylase inhibitor ITF2357 reduces production of pro-inflammatory cytokines in vitro and systemic inflammation in vivo.
London, UK
2 hours ago
1 Received
- The study focused on ITF2357, a synthetic inhibitor of histone deacetylases (HDACs), which can enhance gene expression by unraveling chromatin and is being evaluated for its anti-inflammatory properties.
- ITF2357 significantly reduced the release of pro-inflammatory cytokines such as TNFalpha and IFNgamma in lab-cultured human blood cells, while showing no effect on IL-8 levels and not causing cell death.
- In experiments with mice, oral doses of ITF2357 lowered TNFalpha and IFNgamma levels in serum and helped reduce liver damage from hepatitis without affecting other induced cytokines, indicating its potential as an anti-inflammatory agent.
$100 - $150
Hourly Rate
Histone deacetylase inhibitor ITF2357 is neuroprotective, improves functional recovery, and induces glial apoptosis following experimental traumatic brain injury.
London, UK
2 hours ago
1 Received
- Despite ongoing research for traumatic brain injury (TBI) treatments, there are currently no specific pharmacological options available; this study highlights the potential of ITF2357, a pan-HDAC inhibitor shown to be safe in humans.
- Administering ITF2357 24 hours after a closed head injury in mice led to significant improvements in neurobehavioral recovery and reduced tissue damage, evidenced by decreased neuronal degeneration and lesion volume.
- The treatment also enhanced certain protective cellular markers and promoted apoptosis in harmful glial cells, suggesting ITF2357's role in reducing functional deficits from brain trauma and its potential as a therapeutic option.
$100 - $150
Hourly Rate
A phase II multiple dose clinical trial of histone deacetylase inhibitor ITF2357 in patients with relapsed or progressive multiple myeloma.
London, UK
2 hours ago
1 Received
- ITF2357 is an oral histone deacetylase inhibitor that effectively induces cell death in multiple myeloma (MM) cells.
- A phase-II clinical trial with 19 patients aimed to find the maximum tolerated dose (MTD) of ITF2357, resulting in a MTD of 100 mg taken twice daily after initial dose-limiting toxicities were observed at 150 mg.
- The treatment was generally tolerable, with some serious side effects reported, but showed limited clinical effectiveness, as most patients experienced disease progression or died by the last follow-up.
$100 - $150
Hourly Rate
Pleiotropic anti-myeloma activity of ITF2357: inhibition of interleukin-6 receptor signaling and repression of miR-19a and miR-19b.
London, UK
2 hours ago
1 Received
- - ITF2357, a histone deacetylase inhibitor, shows strong cytotoxic effects against multiple myeloma and is currently being tested in clinical trials for this condition.
- - Gene expression profiling of myeloma cells treated with ITF2357 revealed significant changes, identifying 140 and 574 up-regulated genes and 102 and 556 down-modulated genes after 2 and 6 hours, with key changes in genes related to transcription and apoptosis.
- - The drug specifically decreased the expression of the interleukin-6 receptor alpha (CD126) and affected associated signaling pathways, suggesting ITF2357 disrupts mechanisms crucial for myeloma cell growth and survival.
$100 - $150
Hourly Rate
The histone deacetylase inhibitor ITF2357 decreases surface CXCR4 and CCR5 expression on CD4(+) T-cells and monocytes and is superior to valproic acid for latent HIV-1 expression in vitro.
London, UK
2 hours ago
1 Received
- Chromatin-associated repression helps maintain HIV-1 latency, and inhibiting histone deacetylases (HDAC) can reactivate the virus from quiescent cells.
- The study compared the effects of ITF2357 (an effective HDAC inhibitor) with valproic acid (VPA) to see which better triggers HIV-1 expression in latently infected cells.
- Results showed ITF2357 significantly increased viral protein expression compared to VPA and also decreased a specific cell surface receptor (CXCR4), making it a promising option for clinical HIV-1 treatment.
$100 - $150
Hourly Rate
A pilot study of the Histone-Deacetylase inhibitor Givinostat in patients with JAK2V617F positive chronic myeloproliferative neoplasms.
London, UK
2 hours ago
1 Received
- A phase II study assessed the safety and effectiveness of Givinostat, a histone-deacetylase inhibitor, in patients with Polycythaemia Vera, Essential Thrombocythaemia, and Myelofibrosis who have the JAK2V617F mutation.
- The treatment involved administering Givinostat orally for 24 weeks, with some patients requiring dose adjustments or discontinuation due to side effects or disease progression.
- Results showed promising responses, especially among Polycythaemia Vera and Essential Thrombocythaemia patients, with improvements in symptoms like pruritus and splenomegaly, indicating Givinostat's potential as a tolerated treatment option.
$100 - $150
Hourly Rate
ITF2357 interferes with apoptosis and inflammatory pathways in the HL-60 model: a gene expression study.
London, UK
2 hours ago
1 Received
- - The study investigated the effects of ITF2357, a histone deacetylase inhibitor, on HL-60 acute myeloid leukemia cells, revealing it causes significant cell growth inhibition and promotes apoptosis (cell death).
- - ITF2357 decreased protein levels of anti-apoptotic factors (BCL-2, MCL-1, BCL-X) while increasing pro-apoptotic factors (BAK) without affecting NF-κB DNA binding activity.
- - Microarray analysis identified several deregulated pathways related to inflammation and cell signaling, indicating ITF2357's potential for therapeutic applications in treating leukemia.
$100 - $150
Hourly Rate
Safety and efficacy of an oral histone deacetylase inhibitor in systemic-onset juvenile idiopathic arthritis.
London, UK
2 hours ago
1 Received
- The study aimed to assess the safety and effectiveness of the oral drug givinostat in treating systemic-onset juvenile idiopathic arthritis (JIA) in 17 patients over 12 weeks.
- Results indicated that givinostat was generally safe, with most adverse effects being mild and resolving on their own; only three patients experienced drug-related side effects.
- At the end of the study, a majority of participants showed significant improvements in disease symptoms, particularly in reducing the number of affected joints.
$100 - $150
Hourly Rate
Pharmacokinetics, safety and inducible cytokine responses during a phase 1 trial of the oral histone deacetylase inhibitor ITF2357 (givinostat).
London, UK
2 hours ago
1 Received
- * The trial showed that the drug was generally safe at doses of 50 and 100 mg, with a slight, temporary drop in platelet count that returned to normal after 14 days, and no serious side effects or organ toxicity were reported.
- * Additionally, the medication effectively reduced the production of certain pro-inflammatory cytokines shortly after dosing, although these levels returned to baseline within 12 hours, indicating a consistent but short-lived effect.
$100 - $150
Hourly Rate
Histone deacetylase inhibitors for treating a spectrum of diseases not related to cancer.
London, UK
2 hours ago
1 Received
- - This issue of Molecular Medicine discusses 14 reports on histone deacetylase inhibitors (HDACi's) and their potential therapeutic uses beyond cancer treatment, particularly focusing on their anti-inflammatory properties.
- - HDACi's have shown effectiveness in reducing cytokine production and signaling, and they have been tested in various models, including neurodegenerative disorders and autoimmune diseases like arthritis, with low doses being well tolerated.
- - The article highlights that there isn’t a single mechanism for the effects of HDACi's; instead, it depends on the specific disease process and cell types, suggesting that these inhibitors could be promising candidates for chronic inflammatory disease therapies.
$100 - $150
Hourly Rate
Inhibition of histone deacetylases in inflammatory bowel diseases.
London, UK
2 hours ago
1 Received
- - This review discusses how histone deacetylase (HDAC) inhibitors, particularly SAHA and ITF2357, can alleviate intestinal inflammation and reduce cancer risk associated with inflammation, based on both new and existing data.
- - In experiments with mice, these HDAC inhibitors improved colitis symptoms and lowered inflammatory markers, while also diminishing the number and size of tumors in models linked to inflammation-driven cancer.
- - The findings suggest that HDAC inhibitors could be a beneficial treatment for human inflammatory bowel disease, as the safe dosages in humans match those effective in the mice studies.
$100 - $150
Hourly Rate