vactosertib (TEW-7197)

Similar re-sensitizing effects of mitoxantrone were also observed in colony formation and multicellular tumor spheroid assays. In addition to functional inhibition, vactosertib reduced the expression levels in both ABCG2 mRNA and protein without altering membrane localization, suggesting transcriptional downregulation. As a result, these findings indicate that vactosertib reverses ABCG2-mediated MDR through dual effects on inhibiting ABCG2 function and downregulating and the expression of ABCG2, supporting its potency as a chemo sensitizing agent in ABCG2-mediated MDR cancer models.

We evaluated the antitumor effect of the combination therapy with osimertinib and either nintedanib (an indirect TGF-β inhibitor) or vactosertib (a specific TGF-β type I receptor kinase inhibitor). In conclusion, combination therapy with osimertinib and TGF-β inhibitors potentiates osimertinib-induced antitumor immunity. These findings highlight a novel therapeutic strategy for EGFR-mutated NSCLC and warrant further clinical investigation.

P2, N=6, Terminated, Chloe Atreya, MD, PhD | Trial completion date: Apr 2026 --> Sep 2025 | Active, not recruiting --> Terminated | Trial primary completion date: Apr 2026 --> Sep 2025; Sponsor decision

Sorafenib, lenvatinib and atorvastatin also affected chemokine and cytokine release. Tocilizumab, galunisertib, and vactosertib decreased the level of IL6, a relevant prognostic marker for HCC, while IL6 was increased by halofuginone. In conclusion, HCC PDChip models enabled a detailed evaluation of drug-induced responses in the tumor and associated microenvironment, highlighting their importance in preclinical research for understanding diseases and developing new drugs.

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