Iclusig (ponatinib)

Collectively, our findings demonstrate the therapeutic efficacy of ponatinib in FGFR3-expressing MM beyond selective FGFR3 inhibition, suggesting that concurrent suppression of multiple signaling pathways is a critical mechanism of action. These results highlight the therapeutic potential of combined FGFR3-targeted strategies in multiple myeloma and provide a rationale for further clinical investigation.

Ponatinib emerged as the top-ranked computational candidate (mean: - 10.07 kcal/mol), followed by Regorafenib (- 9.64), Sorafenib (- 9.46), and Entrectinib (- 9.45), while non-oncology drugs including antrafenine, betrixaban, and maraviroc demonstrated novel multi-target binding profiles...MM-GBSA calculations revealed a binding hierarchy concordant with docking scores (R2 = 0.92): Ponatinib-VEGFR2 (ΔGbind = - 42.38 kcal/mol) > Entrectinib-CDK6 (- 38.56) > Ponatinib-EGFR (- 33.24) > Entrectinib-HER2 (- 28.47) > Dacomitinib-HDAC3 (- 24.63 kcal/mol)...As the present study is entirely computational, the identified compounds should be regarded as hypothesis generating leads requiring experimental validation through in vitro kinase and HDAC3 inhibition assays, cell based studies, and target engagement confirmation before any translational conclusions can be drawn. The online version contains supplementary material available at 10.1007/s40203-026-00681-w.

P2, N=25, Recruiting, University Health Network, Toronto | Not yet recruiting --> Recruiting

Interestingly, 5 almost completely retained the efficacy of ponatinib in inhibiting colony formation by MDA-MB-231 breast cancer cells. These results might support the development of novel ponatinib analogs toward therapeutic kinase inhibitors with improved pharmacological properties.

As a result, we found that any possible 2-drug combination of venetoclax, ponatinib, and trametinib was highly synergistic in vitro. Regrettably, none of the synergistic 2-drug combinations appeared sufficiently effective in preventing leukemia outgrowth in our PDX models, which likely requires combinations of >2 drugs. Hence, our results illustrate/signify that straightforward high-throughput combinatorial drug screening in leukemia cell lines is a valid approach to identify synergistic drug combinations that are verifiable in vivo in PDX mouse models without requiring validation in primary patient cells in vitro.

ISR activation and RIPK3-mediated necroptosis converge to drive epithelial injury and barrier dysfunction in CD. Repurposing pazopanib and ponatinib offers a potentially translatable approach to restore barrier integrity in CD.

P1/2, N=67, Completed, Fondazione Gimema Franco Mandelli Onlus | Active, not recruiting --> Completed

P1, N=56, Recruiting, Sun Pharmaceutical Industries Limited | Not yet recruiting --> Recruiting

P2, N=25, Recruiting, University of Chicago | Suspended --> Recruiting | Trial completion date: Mar 2027 --> Mar 2028 | Trial primary completion date: Mar 2027 --> Mar 2028

P2, N=20, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed | Trial completion date: Nov 2026 --> Jun 2026 | Trial primary completion date: Nov 2026 --> Jun 2026

P1/2, N=30, Not yet recruiting, Grupo Espanol De Leucemia Mieloide Cronica (GELMC)

P1, N=26, Not yet recruiting, Wake Forest University Health Sciences