This study highlights potential metabolite signatures associated with in vitro SYK-targeted therapy in AML. These findings support future research to identify potential serum biomarkers, guiding personalized SYK inhibition strategies in AML.

First-generation inhibitors, such as midostaurin, provided the foundation for targeted therapy, while recently developed agents such as gilteritinib and quizartinib have shown more selectivity and demonstrated superior clinical efficiency and improved tolerability. This review discusses the significance of FLT-3 mutations, the evolution of targeted therapies, current treatment guidelines, and ongoing challenges such as resistance and high relapse rates. We also discuss the emerging combinations of therapies and novel agents currently in clinical trials that aim to overcome resistance and improve long-term outcomes for patients with FLT-3-mutated AML.

Finally, we demonstrated the efficacy of TUS plus PMB therapy in a mouse model of pulmonary infection with a clinical PMB-resistant K. pneumoniae isolate. In all, this work discovers a promising drug combination strategy based on PMB and TUS and underlies the special mode of action that involves inhibiting the activity of NagA.

P3, N=106, Completed, Arog Pharmaceuticals, Inc. | Recruiting --> Completed | N=322 --> 106 | Trial completion date: Oct 2024 --> Apr 2026 | Trial primary completion date: Oct 2024 --> Apr 2026

P3, N=214, Completed, Arog Pharmaceuticals, Inc. | Recruiting --> Completed | N=510 --> 214 | Trial completion date: Nov 2024 --> Apr 2026 | Trial primary completion date: Nov 2022 --> Apr 2026

While no JAK inhibitor has demonstrated clear disease-modifying effects in MF, pacritinib's non-myelosuppressive profile, unique activity against IRAK1, and potential anemia benefit via ACVR1 inhibition suggests potential utility as a backbone for future combination strategies. Ongoing and future studies will be critical to further define its role in phenotype-driven MF management.

P2, N=64, Recruiting, Chengdu Zenitar Biomedical Technology Co., Ltd | Not yet recruiting --> Recruiting

P2, N=30, Completed, Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest | Active, not recruiting --> Completed | Trial completion date: Jun 2026 --> Jan 2026 | Trial primary completion date: Mar 2026 --> Nov 2025

PLD1-inhibitor remodeled phospholipid metabolism, induced ferroptosis and restored QUIZOM response in LSC. Our findings provided the therapeutic and resistant mechanisms of QUIZOM and paved the way for targeted interventions in this AML subtype.

P1, N=12, Recruiting, Daiichi Sankyo | Trial completion date: Mar 2026 --> Oct 2026 | Trial primary completion date: Mar 2026 --> Oct 2026

Four protein kinase inhibitors, R547, GDC-0879, JNJ-7706621 and ABT-869 were found to bind hPIP5K1α via a stable complex formation. The hit molecules display favorable ADME properties and are predicted to be non-carcinogenic. The hit molecules in particular R547, have better binding free energies compared to reference molecule, ISA-2011B.

P1, N=69, Recruiting, Emory University | Trial primary completion date: Dec 2025 --> Dec 2026