Iclusig (ponatinib)

The pharmacokinetics study strengthened our results that the identified drugs can be used as a therapeutic for PDAC as they obey Lipinski's rule. In conclusion, identified genes can act as prognostic markers, and drugs could be used as potential therapeutics for PDAC.

Combination strategies, such as vorinostat with ponatinib, provide complementary therapeutic avenues...Hybrid molecules derived from approved TKIs, including GNF-7, olverembatinib, and HG-7-85-01, exemplify rational design trends that balance efficacy with improved safety. Molecular modeling continues to deepen understanding of ligand engagement within the T315I-mutated active site, supporting the development of next-generation inhibitors. In this review, we summarized recent progress in the design, optimization, and biological evaluation of small molecules targeting the BCR-ABLT315I mutation.

Patients remaining on dasatinib maintained elevated NK cells with a more mature phenotype, suggesting a durable effect. These results highlight the greater dasa+blina immune activation, supporting a potential synergistic effect of the drug combination.

Molecular docking results revealed that C5 exhibited robust hydrogen bond interactions with specific amino acid residues in the Imatinib-Bcr-AblWT and Ponatinib-Bcr-AblT315I protein kinase models, suggesting a plausible binding model based on the docking scores. The findings suggest that C5 exhibits promising potential as a highly efficacious for an anti-leukemia agent, thereby providing a valuable avenue for further exploration and application.

P=N/A, N=103, Not yet recruiting, Gruppo Italiano Malattie EMatologiche dell'Adulto

Asciminib has shown efficacy in heavily pretreated patients and in the first-line setting, but resistance and limited benefit after ponatinib highlight the need for new therapeutic options...TGRX-678 exhibits potent activity against wild-type and mutant ABL1, including T315I, synergism with orthosteric tyrosine kinase inhibitors (TKIs), central nervous system (CNS) penetration, and encouraging phase Ia/Ib clinical activity in heavily pretreated CML. Early but promising data are also emerging for TERN-701 from the CARDINAL trial...Key questions regarding durability, long-term safety, and optimal integration with ATP-competitive TKIs remain open. Ongoing trials will define the clinical role of these STAMPi and their potential to advance cure-directed strategies, including treatment-free remission.

Patients who remained relapse-free one year after ponatinib discontinuation exhibited higher levels of NK and NKT-like cells with degranulation capacity. Consolidation with ponatinib showed a high TFR rate and adequate safety, granting further research.

Individualized dosing strategies are essential to balance efficacy and cardiovascular safety. Ponatinib remains a valuable bridging therapy for patients requiring allogeneic transplantation.

Kinase inhibitor screens identify NVP-AST487 and ponatinib as selective CDK10 inhibitors. Clinically, low CDK10 expression in tumors correlates with better immunotherapy responses. These findings establish CDK10 as a pivotal modulator of tumor immunity and a potential therapeutic target.

Particular attention is paid to how STAMP inhibition differs from ATP-competitive TKIs in terms of selectivity, toxicity profile, and resistance patterns, and how asciminib can be positioned relative to ponatinib in later-line settings.Asciminib has established itself as an effective and generally well-tolerated option for patients with TKI-resistant or -intolerant CML and is poised to expand into earlier lines of therapy. Its ability to induce rapid and deep molecular responses with reduced off-target toxicity may have important implications for long-term disease control and future treatment-free remission (TFR) strategies. Ongoing studies will clarify its optimal sequencing, combination potential, and role in facilitating durable TFR.

Thus, dasatinib could be used to minimize potential CAR123 toxicity toward endothelial cells without compromising its anti-leukemic effects. However, a higher dose could be used to completely inhibit CAR-T cell functionality in the event of toxicity.

These results suggest that BMP-7 might inhibit PON-induced cardiotoxicity. Furthermore, our findings pave the way for future translational studies with BMP-7, which can demonstrate the therapeutic potential of BMP-7 in a clinical setting.