Ojjaara (momelotinib)
Research Synopsis
- Recent studies have shown that momelotinib (Ojjaara) is effective in treating myelofibrosis patients who suffer from severe anemia, providing a viable alternative to traditional blood transfusions.
- JAK inhibitors like momelotinib target specific mutations, such as JAK2(V617F), crucial in managing myeloproliferative neoplasms, including myelofibrosis and polycythemia vera.
- Clinical research has demonstrated that momelotinib significantly improves spleen size and anemia symptoms, offering enhanced quality of life for patients compared to older treatment options.
- Despite its benefits, the exact long-term impact of momelotinib on disease progression requires further investigation to avoid relying solely on monotherapy approaches.
- Studies indicate momelotinib and other JAK inhibitors do not completely eliminate target mutations but can mitigate symptoms and reduce inflammatory cytokines in treated patients.
- Safe and effective dosing strategies continue to be a focus, with ongoing clinical trials exploring the optimal administration of momelotinib in combination with other therapies.
- Recent reviews highlight the need for personalized treatment strategies considering the diverse molecular profiles of patients with myelofibrosis.
- There are indications that momelotinib may have broader applications beyond myelofibrosis, showing promise against other malignancies by inhibiting key signaling pathways involved in cancer cell growth.
- The development and validation of reliable pharmacokinetic assays are crucial for accurately assessing momelotinib’s efficacy and ensuring appropriate treatment levels in different patient populations.
- As the research evolves, momelotinib stands out as a critical component in the expanding array of therapies available for myeloproliferative neoplasms, necessitating continued exploration and clinical application.
Ojjaara (momelotinib)
How I individualize selection of JAK inhibitors for patients with myelofibrosis.
London, UK
2 hours ago
1 Received
- JAK inhibitors (JAKi) are new medicines used to treat a serious blood disease called myelofibrosis (MF), helping patients live better lives.
- The first JAKi, ruxolitinib, was approved in 2011 and helped control symptoms like an enlarged spleen and boosted survival rates.
- Two other JAK inhibitors, pacritinib and momelotinib, are useful for patients with specific issues like severe anemia and can help people avoid blood transfusions.
$100 - $150
Hourly Rate
Treatment of anemia in myelofibrosis: focusing on novel therapeutic options.
London, UK
2 hours ago
1 Received
- Myelofibrosis is a disease where the body makes too many stem cells, leading to issues like anemia and enlarged organs.
- This review talks about new treatments for anemia in myelofibrosis, including different types of medicine that help fight the disease.
- Experts say that current treatments don't work very well and can be harmful, but new drugs are showing better results and can help patients improve.
$100 - $150
Hourly Rate
Phenylaminopyrimidines as inhibitors of Janus kinases (JAKs).
London, UK
2 hours ago
1 Received
- A new group of phenylaminopyrimidines has been discovered as inhibitors for Janus kinases (JAKs), which are important targets in various diseases.
- The research focused on the creation of a specific inhibitor called CYT387, which effectively targets both JAK2 and JAK1.
- The study includes detailed information about how these compounds were synthesized and the structure-activity relationship (SAR) that was established during the research.
$100 - $150
Hourly Rate
CYT387, a novel JAK2 inhibitor, induces hematologic responses and normalizes inflammatory cytokines in murine myeloproliferative neoplasms.
London, UK
2 hours ago
1 Received
- Activating mutations in Janus kinase 2 (JAK2) like JAK2(V617F) play a key role in myeloproliferative neoplasms (MPNs), indicating that JAK2 inhibitors could be effective treatments.
- A compound called CYT387 effectively inhibits JAK1, JAK2, and TYK2, and has been shown to suppress growth and induce cell death in JAK2-dependent cancer cell lines without affecting non-cancerous cells.
- Although CYT387 demonstrated positive effects in reducing symptoms and inflammatory markers in a mouse model, it could not fully eliminate JAK2(V617F) cells, highlighting that JAK2 inhibitor monotherapy may not be curative
$100 - $150
Hourly Rate
Targeting myeloproliferative neoplasms with JAK inhibitors.
London, UK
2 hours ago
1 Received
- The review discusses the impact of JAK2V617F and other mutations on the treatment of myeloproliferative neoplasms (MPN) and the development of JAK inhibitors, focusing on their use in myelofibrosis and polycythemia vera/essential thrombocythemia.
- Despite showing clinically meaningful benefits like reduced spleen size and improved symptoms, JAK inhibitors have not demonstrated significant disease-modifying effects in MPN patients.
- Ongoing challenges include defining the optimal dosing strategies, establishing combination therapies with other treatments, and identifying primary end-points for labeling the efficacy of JAK inhibitors in these conditions.
$100 - $150
Hourly Rate
The novel JAK inhibitor CYT387 suppresses multiple signalling pathways, prevents proliferation and induces apoptosis in phenotypically diverse myeloma cells.
London, UK
2 hours ago
1 Received
- Janus kinases (JAKs) are critical in the signaling pathways of malignant cells, particularly in multiple myeloma (MM), where the IL-6/JAK/STAT pathway contributes to drug resistance.
- The novel JAK1/2 inhibitor CYT387 shows promise in treating MM by preventing IL-6-induced signaling and reducing cell proliferation in various human myeloma cell lines.
- CYT387 not only induces apoptosis in these cell lines and primary patient cells but also enhances the effectiveness of traditional MM therapies like melphalan and bortezomib when used in combination.
$100 - $150
Hourly Rate
Incyte comes of age with JAK inhibitor approval.
London, UK
2 hours ago
1 Received
$100 - $150
Hourly Rate
New generation small-molecule inhibitors in myeloproliferative neoplasms.
London, UK
2 hours ago
1 Received
- Myeloproliferative neoplasms (MPNs) often have a common mutation (JAK2 V617F) in about 70% of cases, leading to a focus on developing targeted therapies with JAK2 inhibitors.
- Recent research has identified several drugs targeting crucial pathways for MPN development, including JAK-STAT and PI3K/AKT/mTOR, which have shown effectiveness in reducing spleen size and alleviating symptoms.
- JAK2 inhibitors are particularly beneficial for patients with splenomegaly or constitutional symptoms, but those with low hemoglobin levels need to be cautious as the treatment may temporarily increase the need for blood transfusions.
$100 - $150
Hourly Rate
JAK2 inhibitors and their impact in myeloproliferative neoplasms.
London, UK
2 hours ago
1 Received
- The BCR-ABL-negative myeloproliferative neoplasms (MPNs) consist of essential thrombocythemia, polycythemia vera, and primary myelofibrosis, which have historically presented treatment challenges due to their complex biochemical changes.
- The discovery of Janus kinase (JAK) mutations in these MPNs has sparked interest in targeted treatments, leading to the development of JAK2 inhibitors like INCB018424 and CYT387 that show potential in improving symptoms and reducing spleen size.
- Despite the promise of these therapies, there is still no evidence of complete or partial remission, leaving important questions about optimal treatment guidelines and the overall effectiveness of JAK2 inhibitors.
$100 - $150
Hourly Rate
Liquid chromatography-tandem mass spectrometric assay for the JAK2 inhibitor CYT387 in plasma.
London, UK
2 hours ago
1 Received
- * The assay involved a chromatography system with a specialized column and gradient involving formic acid in water and methanol for effective separation and detection of CYT387.
- * Results showed the assay had a calibration range of 0.25-1000 ng/ml, with good precision (3.0-14.5%) and accuracy (96%-113%), indicating it can reliably assess drug levels in biological samples like those from mice.
$100 - $150
Hourly Rate
Liquid chromatography-tandem mass spectrometric assay for the VEGFR inhibitor cediranib and its primary human metabolite cediranib-N⁺-glucuronide in plasma.
London, UK
2 hours ago
1 Received
- A new quantitative bioanalytical assay was developed and validated to measure cediranib and its metabolite in human plasma.
- The assay involved protein precipitation, followed by chromatography and mass spectrometry, using specific internal standards for accurate detection.
- Validation results showed reliable precision and accuracy for both compounds, and the assay was effectively applied in a pharmacokinetic study on mice.
$100 - $150
Hourly Rate
Current outlook on molecular pathogenesis and treatment of myeloproliferative neoplasms.
London, UK
2 hours ago
1 Received
- * New mutations have been identified in genes related to the JAK-STAT pathway and epigenetic regulation, indicating a need for further research on their pathogenetic roles in MPNs.
- * Numerous JAK kinase inhibitors are in clinical trials, with recent approvals for PMF; however, their long-term effects on disease progression and comparison to standard therapies need further exploration.
$100 - $150
Hourly Rate
JAK2 inhibitors for myelofibrosis: why are they effective in patients with and without JAK2V617F mutation?
London, UK
2 hours ago
1 Received
- A mutation known as JAK2V617F is found in 90% of patients with polycythemia vera and 50% of those with essential thrombocythemia and primary myelofibrosis, driving the use of JAK2 inhibitors in treatment.
- JAK2 inhibitors target the ATP binding site, affecting both mutated and normal kinases, which has shown to improve symptoms and spleen size in patients during clinical trials.
- The drugs are thought to work by not only stopping cancer cell growth but also reducing inflammation by downregulating certain cytokine receptors, making them potentially beneficial for a broader range of patients.
$100 - $150
Hourly Rate
Myelofibrosis, JAK2 inhibitors and erythropoiesis.
London, UK
2 hours ago
1 Received
$100 - $150
Hourly Rate
Safety and efficacy of CYT387, a JAK1 and JAK2 inhibitor, in myelofibrosis.
London, UK
2 hours ago
1 Received
- JAK-STAT pathway is a targeted approach for treating myelofibrosis (MF) due to its link with mutations and inflammatory cytokines.
- The Phase 1/2 trial of CYT387, a JAK1/2 inhibitor, involved 60 MF patients, showing a maximum-tolerated dose of 300 mg/day and significant anemia and spleen responses.
- Most patients reported improvement in symptoms, while common adverse effects included thrombocytopenia and peripheral neuropathy, but CYT387 was overall well tolerated and showed promising efficacy.
$100 - $150
Hourly Rate
P-glycoprotein (MDR1/ABCB1) and breast cancer resistance protein (BCRP/ABCG2) restrict brain accumulation of the JAK1/2 inhibitor, CYT387.
London, UK
2 hours ago
1 Received
- - CYT387 is a small molecule that inhibits JAK1 and JAK2 and is being tested for treating myelofibrosis and related conditions in clinical trials.
- - The study investigated the role of drug transporters P-glycoprotein (MDR1) and breast cancer resistance protein (BCRP) in affecting the oral availability and ability of CYT387 to penetrate the brain.
- - Results showed that while oral availability was not significantly limited by these transporters, brain accumulation of CYT387 was greatly increased in mice lacking both transporters, highlighting their significant role in restricting brain penetration and potentially impacting the drug's effectiveness against brain metastases.
$100 - $150
Hourly Rate
The new landscape of therapy for myelofibrosis.
London, UK
2 hours ago
1 Received
- * Ruxolitinib became the first approved drug for MF, showing significant benefits in symptom relief, spleen size reduction, and survival, with more JAK2 inhibitors like fedratinib and pacritinib entering phase III testing.
- * Ongoing research is exploring various therapies, including immunomodulators and combination strategies, aiming to improve the management of MF and enhance individualized treatment plans for patients.
$100 - $150
Hourly Rate
Emerging therapies for the treatment of chronic Philadelphia chromosome-negative myeloproliferative neoplasm-associated myelofibrosis.
London, UK
2 hours ago
1 Received
- Chronic Philadelphia chromosome-negative myeloproliferative neoplasm-associated myelofibrosis leads to serious health issues like severe anemia, enlarged spleen, and reduced survival, but the JAK2 inhibitor ruxolitinib has shown improvements in some patients.
- Recent research is exploring new treatment options, including additional JAK2 inhibitors (like fedratinib and pacritinib) and combination therapies to enhance effectiveness against symptoms and improve patient outcomes.
- Ongoing and future clinical trials are focused on innovative treatments, including advanced JAK2 therapies and immunomodulation strategies, to better address the needs of patients with this condition.
$100 - $150
Hourly Rate
Inhibition of KRAS-driven tumorigenicity by interruption of an autocrine cytokine circuit.
London, UK
2 hours ago
1 Received
- KRAS, a key player in tumor development, activates additional pathways beyond MAPK and PI3K, which are crucial for tumor maintenance.
- Researchers found that the kinases TBK1 and IKKε support KRAS-driven tumor growth by regulating the release of cytokines like CCL5 and IL-6.
- The drug CYT387 effectively inhibits these signaling pathways, leading to reduced tumor growth and enhanced treatment effects when combined with MAPK inhibition in mouse models of lung cancer.
$100 - $150
Hourly Rate
Inhibition of the JAK2/STAT3 pathway in ovarian cancer results in the loss of cancer stem cell-like characteristics and a reduced tumor burden.
London, UK
2 hours ago
1 Received
- - Ovarian cancer treatment with chemotherapy leads to residual tumors that can develop into cancer stem cell-like populations, increasing the likelihood of recurrence, as shown in prior studies.
- - In this study, researchers focused on how paclitaxel treatment activates specific signaling pathways (JAK2/STAT3) in ovarian cancer cells, leading to the survival and enrichment of these cancer stem cell-like cells.
- - Treatment with a small molecule inhibitor (CYT387) alongside paclitaxel showed promise by reducing tumor burden and CSC-like characteristics in mouse models, suggesting potential for improved ovarian cancer therapies.
$100 - $150
Hourly Rate