vactosertib (TEW-7197)

While these findings highlight a synergistic anti-MASH effect of THU and EW-7197, the study is positioned as proof-of-concept. Further validation in metabolically relevant models (e.g., HFD/HFHC) and pharmacokinetic analyses are warranted before clinical translation can be considered.

These hits exhibited lower free energies (ΔG) as compared to the benchmark inhibitors, Galunisertib and Vactosertib. The results offer valuable insights into the binding mechanism of protein TGFßR1 and its role in the disease, suggesting that targeting the TGF-ß signaling pathway may represent a promising therapeutic strategy.

This study demonstrates the possibility of targeting TGFBR1 with Galunisertib, Vactosertib, and other prospective ARDS treatments. The findings lay the groundwork for additional experimental validation and the development of innovative therapeutics aimed at reducing ARDS severity.

However, pretreatment with vactosertib unexpectedly induced complete resistance to cytarabine. Importantly, we found that this drug interaction is not unique to TGFBR1 inhibitors, but extends to other clinically significant kinase inhibitors, such as the FLT3 inhibitor midostaurin. These findings may have important implications for optimizing combination therapies in AML treatment.

P2, N=14, Terminated, Yonsei University | N=30 --> 14 | Trial completion date: Dec 2025 --> Mar 2025 | Not yet recruiting --> Terminated | Trial primary completion date: Jul 2025 --> Mar 2025; According to the protocol criteria, during the Phase 1 analysis, the registered participants' imaging evaluation responses did not meet the criteria, leading to an early termination

P1/2, N=120, Completed, MedPacto, Inc. | Active, not recruiting --> Completed | Trial completion date: Jan 2025 --> May 2024

P1/2, N=60, Completed, MedPacto, Inc. | Active, not recruiting --> Completed | Trial completion date: Dec 2024 --> May 2024

P2, N=6, Active, not recruiting, Chloe Atreya, MD, PhD | Recruiting --> Active, not recruiting | N=19 --> 6 | Trial completion date: Jan 2027 --> Apr 2026 | Trial primary completion date: Jan 2027 --> Apr 2026

The method demonstrated a sensitivity of 1.0 ng/mL, linearity ranging from 1.0 to 1000.0 ng/mL, an r2 of 0.999, accuracy ranged between 91.60% and 100.70%, and the drug was found to be stable across all freeze-thaw cycles. The results indicated that the method was selective, accurate, and validated for quantification of vactosertib in biological fluids and pharmacokinetic profiling of vactosertib.

P1/2, N=120, Active, not recruiting, MedPacto, Inc. | Trial completion date: Aug 2024 --> Jan 2025

P2, N=0, Withdrawn, MedPacto, Inc. | N=76 --> 0 | Initiation date: Nov 2021 --> Jun 2021 | Recruiting --> Withdrawn

P2; N=55 --> 11 | Trial completion date: Dec 2025 --> Aug 2024 | Recruiting --> Terminated | Trial primary completion date: Aug 2022 --> Aug 2024; This is because Medpacto decided to modify its development strategy as the business and development environment changed.