Vanflyta (quizartinib)
Research Synopsis
- Vanflyta (quizartinib) is a selective FLT3 inhibitor recently approved for treating newly diagnosed acute myeloid leukemia (AML) patients, particularly those with FLT3-ITD mutations.* -
- Recent trials, including a multicenter phase II study, indicate promising efficacy of quizartinib in combination with high-dose Ara-C and mitoxantrone for relapsed/refractory AML patients, improving complete remission rates compared to historical controls.* -
- Quizartinib has been identified as a potent inhibitor against necroptosis, a regulated form of cell death associated with inflammation-related diseases, indicating its potential application beyond oncology.* -
- Research shows quizartinib effectively inhibits RIPK1, providing protective effects in models of systemic inflammatory response syndrome (SIRS), spotlighting its potential in inflammatory disease treatment.* -
- Ongoing studies are exploring combination treatments with quizartinib, such as pairing it with DHODH inhibitors to enhance efficacy against resistant FLT3-ITD AML variants.* -
- A notable study found quizartinib's effectiveness against specific secondary mutations, suggesting that it can maintain therapeutic efficacy in some drug-resistant cases of AML.* -
- Clinical data reveal common toxicities associated with quizartinib include gastrointestinal and hematological issues, although these are generally manageable within treatment protocols.* -
- The overall response rates for FLT3 inhibitors like quizartinib in AML show an average overall survival of about 9.6 months, suggesting it plays a key role in improving patient outcomes.* -
- Ongoing research focuses on the implications of quizartinib on non-hematologic conditions, highlighting its dual potential in cancer and inflammatory disease contexts.* -
- Future developments in the understanding of FLT3 inhibition are aimed at overcoming resistance mechanisms and improving combination therapeutic strategies for enhanced effectiveness in AML treatment.*
Vanflyta (quizartinib)
Q-HAM: a multicenter upfront randomized phase II trial of quizartinib and high-dose Ara-C plus mitoxantrone in relapsed/refractory AML with FLT3-ITD.
London, UK
2 hours ago
1 Received
- Approximately 50% of older patients with acute myeloid leukemia (AML) do not achieve complete remission after traditional chemotherapy, and alternatives like higher doses of cytarabine combined with mitoxantrone have low success rates, especially for those with the unfavorable FLT3-ITD marker.* -
- This study investigates the efficacy of quizartinib, a selective FLT3 inhibitor, combined with a chemotherapy regimen (HAM) in a randomized phase II trial, assessing outcomes such as complete remission rate compared to historical controls.* -
- The trial employs a novel matched threshold crossing approach to bolster the reliability of results by comparing the current treatment outcomes with data from previous similar studies, aiming to improve the understanding of
$100 - $150
Hourly Rate
Repurposing of Ibrutinib and Quizartinib as potent inhibitors of necroptosis.
London, UK
2 hours ago
1 Received
- Necroptosis is a type of controlled cell death linked to various diseases and is regulated by protein complexes known as necrosomes.
- Researchers screened a library of small compounds and discovered many that inhibit TNF-induced necroptosis, classifying them based on their specific mechanisms of action.
- The study highlighted Ibrutinib as a RIPK3 inhibitor and Quizartinib as a protector against TNF-induced inflammation in mice, indicating potential new treatments for diseases related to necroptosis.
$100 - $150
Hourly Rate
Quizartinib inhibits necroptosis by targeting receptor-interacting serine/threonine protein kinase 1.
London, UK
2 hours ago
1 Received
- * Researchers found that inhibiting a protein called RIPK1 can effectively treat SIRS, identifying the drug quizartinib as a promising candidate through high-throughput screening of FDA-approved drugs.
- * Quizartinib works by directly blocking RIPK1 activity, preventing necroptosis, and demonstrating protective effects in mice with TNFα-induced SIRS, laying the groundwork for its use in treating inflammatory diseases.
$100 - $150
Hourly Rate
[Breakthroughs in FLT3-mutated acute myeloid leukemia treatments].
London, UK
2 hours ago
1 Received
- FMS-like tyrosine kinase 3 (FLT3) mutations are found in 25% of acute myeloid leukemia (AML) cases and are linked to a worse prognosis due to higher relapse rates and shorter remission.
- Two second-generation FLT3 inhibitors, gilteritinib and quizartinib, are used for treating relapsed or refractory FLT3-mutated AML, with quizartinib recently gaining approval in May 2023 for newly diagnosed cases alongside standard therapies.
- There’s ongoing research into using oral FLT3 inhibitors for post-transplant maintenance therapy to address high relapse rates, even after successful allogeneic hematopoietic cell transplantation
$100 - $150
Hourly Rate
Quizartinib (Vanflyta) for acute myeloid leukemia.
London, UK
2 hours ago
1 Received
$100 - $150
Hourly Rate
Blockade of de novo pyrimidine biosynthesis triggers autophagic degradation of oncoprotein FLT3-ITD in acute myeloid leukemia.
London, UK
2 hours ago
1 Received
- * Researchers discovered that blocking the enzyme DHODH, which is important for cell growth, can lead to the degradation of the FLT3-ITD protein, reducing cancer cell survival and activation of harmful signaling pathways.
- * Combining DHODH inhibitors with the FDA-approved FLT3i quizartinib not only enhances treatment efficacy against FLT3-ITD AML cells but also proves effective against quizartinib-resistant variants, suggesting a new therapeutic strategy for AML patients with this mutation.
$100 - $150
Hourly Rate
GNF-7, a novel FLT3 inhibitor, overcomes drug resistance for the treatment of FLT3‑ITD acute myeloid leukemia.
London, UK
2 hours ago
1 Received
- Acute myeloid leukemia (AML) with FLT3-ITD mutation is common and difficult to treat due to poor prognosis and drug resistance, but GNF-7 shows promise as a new treatment option.
- In laboratory studies, GNF-7 demonstrated strong antitumor effects on AML cells with FLT3-ITD, effectively inhibiting cell proliferation and disrupting key signaling pathways.
- GNF-7 also proved effective in overcoming resistance in certain FLT3 mutant cases and improved survival rates in animal models, suggesting potential for clinical use in treating resistant AML.
$100 - $150
Hourly Rate
The FLT3 mutation causes clinical AML resistance to gilteritinib and triggers TKI sensitivity switch to quizartinib.
London, UK
2 hours ago
1 Received
$100 - $150
Hourly Rate
PDP1 is a key metabolic gatekeeper and modulator of drug resistance in FLT3-ITD-positive acute myeloid leukemia.
London, UK
2 hours ago
1 Received
- * FLT3-ITD promotes the expression of PDP1, leading to increased activity of the pyruvate dehydrogenase complex, which drives metabolic shifts essential for cell proliferation and survival under both normoxic and hypoxic conditions.
- * Targeting PDP1 may present a new strategy for overcoming resistance to FLT3 inhibitors, as its regulation affects glucose metabolism and drug response in AML cells.
$100 - $150
Hourly Rate
An imidazo[1,2-a]pyridine-pyridine derivative potently inhibits FLT3-ITD and FLT3-ITD secondary mutants, including gilteritinib-resistant FLT3-ITD/F691L.
London, UK
2 hours ago
1 Received
- About 30% of newly diagnosed acute myeloid leukemia (AML) cases have activating FLT3 mutations, particularly internal tandem duplications (ITDs), which can lead to poor treatment outcomes.
- Three FLT3 inhibitors—midostaurin (first-generation), quizartinib, and gilteritinib (both second-generation)—are currently approved, with the latter two showing improved efficacy but facing resistance due to secondary mutations in the FLT3 gene.
- A new compound, compound 24, was identified as an effective FLT3 inhibitor that works well against both the main FLT3-ITD and resistant mutations (D835Y and F691L), showing potential for better treatment options in AML
$100 - $150
Hourly Rate
Identification of a Selective FLT3 Inhibitor with Low Activity against VEGFR, FGFR, PDGFR, c-KIT, and RET Anti-Targets.
London, UK
2 hours ago
1 Received
- FLT3 is a protein mainly found in immune and cancer cells and is targeted for treating acute myeloid leukemia (AML), but recent studies suggest it could also help with chronic pain.
- Current FLT3 inhibitors (like gilteritinib and midostaurin) can affect other important kinases, making them less ideal for chronic pain treatment and AML maintenance therapy.
- New selective FLT3 inhibitors have been identified that minimally impact these related kinases, providing potential tools for studying FLT3's role in chronic pain and developing better therapies for both AML maintenance and non-cancer applications.
$100 - $150
Hourly Rate
Mapping the proteogenomic landscape enables prediction of drug response in acute myeloid leukemia.
London, UK
2 hours ago
1 Received
- Acute myeloid leukemia (AML) is a challenging cancer to treat due to its complex genetic mutations, which often do not predict how well patients will respond to therapy.
- This study combines multiple data types (proteomic, transcriptomic, and drug sensitivity) from 210 AML patients to uncover new disease subtypes and their drug response patterns beyond just genetic mutations.
- The researchers created a model to predict drug responses tailored to these new subtypes, enhancing treatment strategies and potential drug combinations for AML patients.
$100 - $150
Hourly Rate
Synergy and antagonism between azacitidine and FLT3 inhibitors.
London, UK
2 hours ago
1 Received
- - The study investigates whether combining azacitidine, a demethylation agent for treating unfit AML patients, with FLT3 inhibitors can enhance effectiveness or reduce side effects.
- - Experiments were conducted using human AML cells to assess the interactions between azacitidine and various FLT3 inhibitors (gilteritinib, quizartinib, and others) through dose-response matrices and a scoring algorithm.
- - Results revealed that non-covalent FLT3 inhibitors like gilteritinib and quizartinib showed antagonism when combined with azacitidine, whereas the covalent inhibitor FF-10101 displayed some synergistic effects at certain concentrations.
$100 - $150
Hourly Rate
Properties of FDA-approved small molecule protein kinase inhibitors: A 2024 update.
London, UK
2 hours ago
1 Received
- Protein kinases are crucial drug targets for various diseases, particularly cancers, with 80 FDA-approved drugs that focus on them, including seven approved in 2023.
- Among these drugs, a significant portion treats neoplasms, while others are aimed at inflammatory diseases, showcasing their versatility in treating multiple conditions.
- The review highlights the key physicochemical properties of these 80 small molecule protein kinase inhibitors, covering aspects like potency, solubility, and ligand efficiency to aid in understanding their effectiveness.
$100 - $150
Hourly Rate
Foretinib Is Effective in Acute Myeloid Leukemia by Inhibiting FLT3 and Overcoming Secondary Mutations That Drive Resistance to Quizartinib and Gilteritinib.
London, UK
2 hours ago
1 Received
- FLT3-ITD mutations are common in acute myeloid leukemia (AML) and lead to poor patient outcomes, with current treatments facing challenges from drug resistance.
- Researchers found foretinib to be a more effective FLT3 inhibitor compared to existing drugs, showing stronger results in reducing AML cell growth and improving survival rates in mice.
- Foretinib also combats secondary FLT3 mutations that develop resistance to current therapies, indicating its potential as a promising treatment option for AML patients with FLT3-ITD mutations.
$100 - $150
Hourly Rate
BRCC36 associates with FLT3-ITD to regulate its protein stability and intracellular signaling in acute myeloid leukemia.
London, UK
2 hours ago
1 Received
- Fms-like tyrosine kinase-3 (FLT3) is often mutated in acute myeloid leukemia (AML), with two main types of mutations, FLT3-ITD and FLT3-TKD, having different effects on protein stability and cellular behavior.
- Researchers used TurboID proximity labeling to find that the protein BRCC36 is uniquely associated with the FLT3-ITD mutation and regulates its function differently than the wild type or FLT3-TKD.
- Inhibiting BRCC36 reduces cell growth and increases cell death in FLT3-ITD cells, suggesting that targeting BRCC36 could be a novel strategy for treating AML.
$100 - $150
Hourly Rate
[Correlation of Expression with Drug Sensitivity of Acute Myeloid Leukemia Cell Line and Its Mechanism].
London, UK
2 hours ago
1 Received
- The study aimed to explore how knocking out a specific gene in an acute myeloid leukemia (AML) cell line (MV411) affects the cells' response to anti-leukemia drugs.
- The researchers used CRISPR/Cas9 to create gene knockouts, validated them, and assessed changes in drug sensitivity and molecular signaling pathways through various techniques like RT-qPCR and Western blot.
- Results showed that knocking out the gene increased sensitivity to drugs like doxorubicin and quizartinib, while also inhibiting key signaling pathways (mTOR and Wnt) associated with cancer progression.
$100 - $150
Hourly Rate
The Flt3-inhibitor quizartinib augments apoptosis and promotes maladaptive remodeling after myocardial infarction in mice.
London, UK
2 hours ago
1 Received
- Tyrosine kinase inhibitors (TKIs) like quizartinib, designed to treat acute myeloid leukemia, can also affect the heart, potentially worsening cardiac injury in conditions like myocardial infarction (MI).
- In studies with mice, quizartinib did not change heart dimensions or function but led to increased ventricular dilatation and higher rates of cell death in the heart following MI.
- The findings suggest that quizartinib enhances apoptosis and maladaptive heart remodeling through a mechanism involving the p38 protein, highlighting the need for cardiac monitoring in patients receiving similar treatments.
$100 - $150
Hourly Rate
Efficacy and safety of FLT3 inhibitors in monotherapy of hematological and solid malignancies: a systemic analysis of clinical trials.
London, UK
2 hours ago
1 Received
- FLT3 mutations are linked to blood and solid cancers, particularly acute myeloid leukemia, and several FLT3 inhibitors are currently in trials or use, but their safety and effectiveness have not been thoroughly reviewed.* -
- A review of 13 FLT3 inhibitors revealed common side effects like gastrointestinal issues and hematological problems, with overall survival averaging about 9.6 months and progression-free survival around 5.9 months.* -
- The overall response rate was 29%, with better effectiveness observed in blood cancers compared to solid tumors; combining FLT3 inhibitors with other treatments may enhance their anti-tumor effectiveness.*
$100 - $150
Hourly Rate
Clinico-Radio-Pathologic Correlation of Leukostasis in Acute Myeloid Leukemia with FLT3 Mutation.
London, UK
2 hours ago
1 Received
- Acute hematologic emergencies, particularly leukostasis in acute myeloid leukemia (AML), significantly increase mortality rates due to complications like pulmonary and neurological issues.
- High levels of myeloid blasts in the blood can lead to rapid clinical decline before a proper diagnosis is established.
- This report reviews the relationship between clinical, radiological, and pathological findings in a specific AML patient, while discussing current treatment options, including FLT3 inhibitors like quizartinib.
$100 - $150
Hourly Rate