P=N/A, N=93, Not yet recruiting, Gruppo Italiano Malattie EMatologiche dell'Adulto

Herein, a novel series of PROTAC degraders based on momelotinib were designed and synthesised...Furthermore, in vivo studies demonstrated that A8 significantly reduced inflammatory responses and colon injury by suppressing the JAK/STAT3 signalling pathway. Overall, A8 represents a novel JAK1/2 degrader as a lead compound for IBD for the first time, which deserves further development.

He was started on JAK inhibitor therapy with pacritinib but clinically declined over the next several days with worsening diffuse pain and pancytopenia...Shortly after, the patient presented to an outside hospital with septic shock, at which point the patient expired. This case illustrates the aggressive nature of the disease, the need for confirmatory testing when diagnosis is suspected and the difficulty in management as the prognosis is poor and requires aggressive treatment that can lead to life-threatening sequelae.

P2, N=32, Not yet recruiting, Medical College of Wisconsin

This review examines the role of momelotinib in treating MF, focusing on its mechanism, clinical benefits, patient selection criteria, monitoring strategies, potential side effects, and findings from key clinical trials. While promising, careful patient management is essential to minimize adverse effects and optimize the therapeutic benefits of momelotinib in MF treatment.

P1/2, N=22, Terminated, Incyte Corporation | Completed --> Terminated; Strategic Business Decision

P2, N=113, Active, not recruiting, Clementia Pharmaceuticals Inc. | Trial primary completion date: Jul 2025 --> Mar 2029

Adverse events, including gastrointestinal symptoms, weight loss, and transient voice changes, were manageable through dose adjustments and supportive care, enabling continued therapy. Our cases contribute to the growing body of evidence supporting pacritinib's role in the evolving treatment landscape of MF.

Notably, we found that gastric cancer cells display marked sensitivity to IRAK1/4 inhibitor and pacritinib, the latter targeting JAK2 and IRAK1 specifically, over the pan-JAK inhibitor tofacitinib. Collectively, our results underscore IRAK1 as a promising therapeutic target in gastric cancer. Furthermore, the pharmacological blockade of IRAK1 by pacritinib, an established drug for myelofibrosis and severe thrombocytopenia treatment, holds potential for repurposing in gastric cancer therapy.

Greater TAM exposure was significantly associated with lower odds of grade 3/4 anemia and higher odds of any-grade peripheral neuropathy, although the latter was infrequently observed in phase III trials. There was no significant relationship with grade ≥ 3 thrombocytopenia or any-grade diarrhea.

Post-molecular dynamics simulation MM-GBSA analysis further confirmed these interactions, with binding free energies for FLT3: Kaempferol (-73.75 kcal/mol), Apigenin (-68.76 kcal/mol), Pacritinib (-51.27 kcal/mol); and for PIM1: Tricetin (-64.28 kcal/mol), Diosmetin (-52.2 kcal/mol), SEL24 (-53.38 kcal/mol). FLT3 and MPO were identified as specific diagnostic and prognostic biomarkers for AML. This comprehensive in-silico analysis revealed promising therapeutic compounds from E. prostrata targeting FLT3 and PIM1, along with novel biomarker potentials of FLT3 and MPO for improved AML diagnosis and prognosis, subject to further experimental validation.