Inrebic (fedratinib)

Telmisartan was used as the internal standard (IS). Stability studies confirmed the analyte's integrity across multiple freeze-thaw cycles. The developed LC-MS/MS method is selective, sensitive, fully validated, and was successfully applied to pharmacokinetic studies.

This process can be inhibited by the drug TG-101348. We constructed a risk model with three chemokine-related genes (CRGs), which could effectively predict the prognosis of THCA. Notably, CCL17 expression had a considerable value to the risk model and may promote THCA progression by regulating the JAK-STAT pathway.

P1/2, N=31, Active, not recruiting, Bristol-Myers Squibb | Trial completion date: Oct 2025 --> Nov 2026

P2, N=20, Suspended, Fred Hutchinson Cancer Center | Recruiting --> Suspended | Trial primary completion date: Aug 2026 --> Apr 2027

Nearly 50% of PMF patients experience anemia (hemoglobin (Hb) < 10 g/dL), often worsened by JAK inhibitors like ruxolitinib and fedratinib. However, heterogeneity in control groups limited direct efficacy comparisons. Larger studies are needed to confirm its effectiveness and safety.

P3, N=202, Completed, Celgene | Active, not recruiting --> Completed

Among the four JAK2 inhibitors evaluated (fedratinib, cerdulatinib, peficitinib, and filgotinib), fedratinib significantly inhibited the proliferation of TNBC cells with IC50 values below 2 μM...Notably, combining ceduratinib with either cobimetinib (MEK inhibitor) and ipatasertib (AKT inhibitor) or trametinib (MEK inhibitor) and alpelisib (PI3K inhibitor) mimicked the effects of fedratinib on the cell proliferation, MYC and cyclin D1 suppression, and pro-apoptotic protein induction. These finding suggest that JAK2 inhibition enhances the anticancer effects of concurrent MEK/ERK and PI3K/AKT pathway inhibition, while JAK2 inhibition alone shows minimal efficacy in TNBC cells.

FDB and encorafenib (ENB as the IS) were analyzed using the isocratic mobile phase method on an Eclipse Plus C18 column. In silico screening indicated that minor structural modifications to the pyrrolidine moiety in the process of drug design could increase metabolic stability and enhance safety relative to FDB. The assessment of in silico FDB ADME properties and metabolic stability is important for the progression of novel drug discovery aimed at improving metabolic stability.

Our study identified key genes and related lncRNA-miRNA-mRNA network that contribute to the oncogenesis of glioblastoma.

Therapeutic advancements have focused on JAK2 inhibitors such as ruxolitinib and fedratinib, which show promise in preclinical and early clinical settings. However, challenges such as drug resistance and off-target effects limit their efficacy, necessitating the exploration of combination therapies and novel drug formulations. Current strategies include combining JAK2 inhibitors with chemotherapy, immune checkpoint inhibitors, or epigenetic modulators to achieve synergistic effects.

Moreover, 10i exhibits more potent antiproliferative activity against SET-2 cells than fedratinib and its parent inhibitor WWQ-131...Importantly, 10i suppresses rhEPO-mediated polycythemia and splenomegaly in mice by degrading JAK2 and interfering with the JAK2-STAT signaling pathway. Taken together, the results of this study reveal a promising JAK2 PROTAC degrader for the treatment of MPNs.