Voranigo (vorasidenib)
Research Synopsis
- Vorasidenib (vorasidenib) is emerging as a targeted therapeutic option for low-grade gliomas characterized by mutations in isocitrate dehydrogenase (IDH) 1 and 2.
- Recent research has emphasized its efficacy in reducing levels of the oncometabolite 2-hydroxyglutarate (2-HG) in glioma models and clinical settings.
- Multiple studies, including Phase I trials, indicate that vorasidenib is generally well tolerated and shows promising objective response rates in patients with recurrent low-grade gliomas.
- The INDIGO Phase III trial demonstrated that vorasidenib significantly improves progression-free survival compared to placebo, further solidifying its potential as a frontline treatment.
- Ongoing research is focusing on the optimal selection of patients who could benefit most from vorasidenib, emphasizing the need for molecular profiling in treatment decisions.
- Advanced imaging techniques are being explored to identify metabolic biomarkers indicating treatment response to vorasidenib, particularly through tracking changes in 2-HG levels.
- While vorasidenib offers benefits, studies also highlight the importance of monitoring for potential side effects, which can include dose-limiting toxicity.
- Computational modeling is being utilized to identify new inhibitors that may enhance effects or reduce resistance linked to vorasidenib therapy.
- Overall, vorasidenib is positioned as a promising therapeutic option within the evolving landscape of targeted therapies for IDH-mutant gliomas, with ongoing investigations into its long-term outcomes and clinical effectiveness.
- Nevertheless, further studies are crucial to ascertain the full spectrum of its safety profile and long-term efficacy.
Voranigo (vorasidenib)
Vorasidenib: a new hope or a false promise for patients with low-grade glioma?
London, UK
2 hours ago
1 Received
$100 - $150
Hourly Rate
Validated HPLC method for simultaneous quantification of mutant IDH1/2 inhibitors (enasidenib, ivosidenib and vorasidenib) in mouse plasma: Application to a pharmacokinetic study.
London, UK
2 hours ago
1 Received
- Isocitrate dehydrogenase (IDH) inhibitors are a new class of cancer drugs used for treating acute myeloid leukemia patients with IDH1/2 mutations.
- Researchers developed a high-performance liquid chromatography (HPLC) method to measure levels of three IDH inhibitors—enasidenib (EDB), ivosidenib (IDB), and vorasidenib (VDB)—in mouse plasma, following FDA guidelines.
- The HPLC method showed reliable results with a total run time of 10 minutes, successfully creating a calibration curve and validating the method for use in pharmacokinetic studies in mice.
$100 - $150
Hourly Rate
Vorasidenib (AG-881): A First-in-Class, Brain-Penetrant Dual Inhibitor of Mutant IDH1 and 2 for Treatment of Glioma.
London, UK
2 hours ago
1 Received
- Vorasidenib (AG-881) is a dual inhibitor targeting mutant isocitrate dehydrogenase (mIDH) 1 and 2 enzymes, which are linked to the accumulation of the cancer-related metabolite 2-hydroxyglutarate (2-HG).
- The compound has shown promising results in preclinical studies, effectively penetrating the brain and reducing 2-HG levels by over 97% in glioma models.
- Vorasidenib is currently being tested in clinical trials for treating low-grade gliomas associated with mIDH mutations.
$100 - $150
Hourly Rate
Dual-Knockout of Mutant Isocitrate Dehydrogenase 1 and 2 Subtypes Towards Glioma Therapy: Structural Mechanistic Insights on the Role of Vorasidenib.
London, UK
2 hours ago
1 Received
- Vorasidenib (AG-881) is a promising treatment for low-grade glioma, effectively inhibiting both mIDH1 and mIDH2 enzymes involved in tumor growth.
- The binding of AG-881 is primarily influenced by specific residues (Val255 and Val294) in the binding pockets, which enhance its interaction and binding strength with these enzymes.
- Structural changes caused by AG-881 disrupt key interactions in mIDH1 and mIDH2, reducing their flexibility and limiting their ability to produce the oncogenic metabolite 2-HG, thereby providing insights into its dual inhibition mechanism.
$100 - $150
Hourly Rate
MR-detectable metabolic biomarkers of response to mutant IDH inhibition in low-grade glioma.
London, UK
2 hours ago
1 Received
- Mutations in the IDH1 gene are prevalent in low-grade gliomas and secondary glioblastomas, driving tumor growth through the conversion of α-ketoglutarate to the oncometabolite 2-hydroxyglutarate.
- Inhibitors like AG-120 and AG-881 show promise in treating these tumors, though measuring their effectiveness can be difficult without visible tumor growth changes.
- This study identified potential metabolic imaging biomarkers, specifically using H- and C-magnetic resonance spectroscopy, to track treatment responses by monitoring levels of 2-HG and glutamate in glioma cells.
$100 - $150
Hourly Rate
Vorasidenib, a Dual Inhibitor of Mutant IDH1/2, in Recurrent or Progressive Glioma; Results of a First-in-Human Phase I Trial.
London, UK
2 hours ago
1 Received
- Lower grade gliomas (LGGs) are aggressive brain tumors that often develop resistance to standard therapies, leading to the need for new treatments like vorasidenib, a drug that targets specific mutations in IDH1 and IDH2.
- A phase I clinical trial involving 93 patients with mutant solid tumors, including 52 with glioma, demonstrated that vorasidenib could be taken daily and was generally well tolerated, despite some dose-limiting side effects.
- Results indicated an 18% objective response rate in nonenhancing glioma, with a median progression-free survival of 36.8 months for that group, suggesting that vorasidenib shows promise as a treatment option for recurrent or progressive LGGs
$100 - $150
Hourly Rate
Vorasidenib and ivosidenib in IDH1-mutant low-grade glioma: a randomized, perioperative phase 1 trial.
London, UK
2 hours ago
1 Received
- Vorasidenib and ivosidenib are drugs that target mutant forms of isocitrate dehydrogenase (mIDH) and have shown promise in treating recurrent low-grade gliomas (IGG).
- A Phase 1 trial with 49 patients assessed the effectiveness of these drugs by measuring the reduction of D-2-hydroxyglutarate (2-HG), a byproduct of mIDH enzymes, which dropped significantly following treatment.
- Vorasidenib demonstrated better brain penetrance and more consistent 2-HG suppression than ivosidenib, leading to its selection for further Phase 3 testing.
$100 - $150
Hourly Rate
Pharmacophore-based Identification of Potential Mutant Isocitrate Dehydrogenases I/2 Inhibitors: An Explorative Avenue in Cancer Drug Design.
London, UK
2 hours ago
1 Received
- Heterozygous mutations in isocitrate dehydrogenase 1 and 2 enzymes are targeted for drug development due to their role in increasing the oncometabolite D-2-hydroxyglutarate, which is linked to cancer growth.
- Vorasidenib (AG-881) has shown promise as a dual inhibitor of these enzymes for treating low-grade gliomas, but further research is needed to develop selective inhibitors that minimize drug resistance and toxicity.
- Through computational modeling, two new compounds, ZINC9449923 and ZINC93978407, were identified as leading candidates for targeting the isocitrate dehydrogenase enzymes, displaying favorable binding properties and potential for lower toxicity while penetrating
$100 - $150
Hourly Rate
Imidazole and Biphenyl Derivatives as Anti-cancer Agents for Glioma Therapeutics: Computational Drug Repurposing Strategy.
London, UK
2 hours ago
1 Received
- Targeting mutated isocitrate dehydrogenase 1 (mIDH1) is crucial for glioma treatment, but existing inhibitors face challenges like dose-dependent toxicity and poor brain penetration.
- A study used computational drug repurposing to analyze 11,808 small molecules from DrugBank to find effective mIDH1 inhibitors.
- The research identified three promising compounds (DB12001, DB08026, DB03346) with strong binding affinities and stability towards mIDH1, suggesting their potential for treating recurrent glioblastoma.
$100 - $150
Hourly Rate
Targeted Options for Glioma Looking Good.
London, UK
2 hours ago
1 Received
- The phase III INDIGO trial showed that vorasidenib, an IDH1/2 inhibitor, effectively helps adults with IDH1/2-mutant low-grade gliomas by lowering the risk of disease progression and postponing the need for chemoradiotherapy.
- In a separate pediatric study called FIREFLY-1, a phase II trial, tovorafenib (a type II pan-RAF inhibitor) demonstrated strong responses in children with low-grade gliomas.
- These findings suggest promising treatment options for both adult and pediatric patients dealing with low-grade gliomas, indicating advances in targeted therapies.
$100 - $150
Hourly Rate
Vorasidenib: A promising therapeutic breakthrough for diffuse isocitrate dehydrogenase mutant gliomas.
London, UK
2 hours ago
1 Received
$100 - $150
Hourly Rate
Vorasidenib in IDH1- or IDH2-Mutant Low-Grade Glioma.
London, UK
2 hours ago
1 Received
- Isocitrate dehydrogenase (IDH)-mutant grade 2 gliomas are aggressive brain tumors, and vorasidenib is a promising oral treatment that targets these mutations and showed preliminary effectiveness.
- A randomized phase 3 trial involved 331 patients with untreated residual or recurrent gliomas, comparing vorasidenib to a placebo over 28-day cycles, focusing on progression-free survival as the main outcome.
- Results indicated that patients taking vorasidenib had significantly longer progression-free survival (27.7 months) compared to those on placebo (11.1 months) and experienced better outcomes before needing further treatment, although adverse effects were more common in the vorasidenib group.
$100 - $150
Hourly Rate
Safety, efficacy, and PK/PD of vorasidenib in previously treated patients with mIDH1/2 hematologic malignancies: A phase 1 study.
London, UK
2 hours ago
1 Received
$100 - $150
Hourly Rate
Molecular Profiling and Targeted Therapies in Gliomas.
London, UK
2 hours ago
1 Received
- * Molecular profiling is now a key component of the 2021 WHO classification system for gliomas, but advancements in targeted therapies have faced challenges, such as the blood-brain barrier and tumor diversity.
- * Recent developments include specific therapies for certain genetic mutations in gliomas, like vorasidenib for IDH-mutant gliomas and a combination therapy for BRAFV600E mutated gliomas, but more work is needed to fully harness the potential of these targeted treatments.
$100 - $150
Hourly Rate
What is an isocitrate dehydrogenase-mutated central nervous system World Health Organization grade 2 glioma, or who should receive vorasidenib?
London, UK
2 hours ago
1 Received
$100 - $150
Hourly Rate
Author Correction: Vorasidenib and ivosidenib in IDH1-mutant low-grade glioma: a randomized, perioperative phase 1 trial.
London, UK
2 hours ago
1 Received
$100 - $150
Hourly Rate
Vorasidenib in IDH mutant WHO grade 2 gliomas: time to stop sitting on the fence?
London, UK
2 hours ago
1 Received
$100 - $150
Hourly Rate
Vorasidenib in IDH1/2-mutant low-grade glioma: the grey zone of patient's selection.
London, UK
2 hours ago
1 Received
$100 - $150
Hourly Rate
Ready to INDIGO: Vorasidenib Ushers in the Era of Isocitrate Dehydrogenase Inhibition in Low-Grade Glioma.
London, UK
2 hours ago
1 Received
$100 - $150
Hourly Rate
[Vorasidenib for low-grade gliomas-new treatment option with unanswered questions regarding long-term outcomes].
London, UK
2 hours ago
1 Received
$100 - $150
Hourly Rate