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

Purinergic inhibitory post-junctional motor responses were greatly attenuated in the GI tracts of crenolanib treated animals compared to vehicle treated controls in response to electric field evoked nerve stimulation. These data provide evidence for a functional role of PDGFRα+ cells in inhibitory neuroeffector motor responses throughout the gastrointestinal tract.

P2, N=180, Active, not recruiting, Kyowa Kirin Co., Ltd. | Recruiting --> Active, not recruiting

P2, N=150, Active, not recruiting, Kyowa Kirin Co., Ltd. | Recruiting --> Active, not recruiting

These findings were corroborated by comparative proteomics of EVs derived from AML patients and healthy donors. Ribosomal and ErbB signalling pathway proteins may play an important role in microenvironmental modulation by EVs, and Crenolanib treatment potentially acts by interfering with leukaemia niche formation.

P2, N=180, Recruiting, Kyowa Kirin Co., Ltd. | Trial completion date: Dec 2025 --> Sep 2026 | Trial primary completion date: Nov 2025 --> Aug 2026

P2, N=150, Recruiting, Kyowa Kirin Co., Ltd. | Trial completion date: Dec 2025 --> Sep 2026 | Trial primary completion date: Nov 2025 --> Aug 2026

Additionally, co-treatment of HPA-12 and Crenolanib is effective in FLT3-ITD+ and FLT3-TKD+ AML patients. The synergistic effects are found to be mediated by the endoplasmic reticulum stress-GRP78/ATF6/CHOP axis and mitophagy. Our data provide an effective strategy to enhance the efficacy of FLT3 inhibitors in AML.

Among the promising inhibitors tested, vatalanib, a VEGF-R inhibitor, demonstrated significant in vivo efficacy at inhibiting tumor growth and reducing tumor-associated myeloid cells, thereby underscoring its potential as a therapeutic agent. Our findings highlight specific kinase inhibitors with differential modulatory effects on HNSCC-associated myeloid subsets and caution the application of some as anti-cancer drugs. This experimental system may provide a robust platform for identifying new agents targeting tumor-associated myeloid cells in HNSCC and beyond, and for elucidating mechanistic insights into tumor-myeloid cell interaction.

Finally, we recommended KGs-guided four repurposable drug molecules (Fluoxetine, Vatalanib, TGX221 and RO3306) against GBM through molecular docking, drug likeness, ADMET analyses and molecular dynamics simulation studies. Thus, the discoveries of this study could serve as valuable resources for wet-lab experiments in order to take a proper treatment plan against GBM.

ETN101 remained stable in human CESs. In conclusion, this study provides comprehensive insights into the metabolic characteristics of ETN101, valuable for its toxicological and clinical development.