An inhibition of SHH signaling by cyclopamine or GANT61 entirely normalized the differentiation deficit of Rxrg-/- OPCs, but also myelination of newly generated Rxrg-/- OLs...Importantly, hyperactivation of the SHH pathway by purmorphamine or SAG inhibited the oligodendrogenesis and myelination potential of wild-type OPCs, indicating that SHH hyperactivity can also be a sufficient factor to block OPC differentiation. These results point to RXRg as an important regulator of SHH pathway signaling and underline the need of an optimal, fine-tuning of SHH signaling to assure successful oligodendrogenesis.

P1, N=55, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2026 --> Mar 2027

P1, N=36, Active, not recruiting, Mayo Clinic | Trial completion date: Nov 2026 --> Jul 2027 | Trial primary completion date: Jan 2026 --> May 2025

Dysgeusia and alopecia occurred with daily dosing, whereas every-other-day dosing was well tolerated. This case highlights the value of transcript-level functional assays for interpreting PTCH1 splice-site variants and supports individualized, toxicity-guided sonidegib scheduling in selected patients with Gorlin-Goltz syndrome.

P1, N=57, Not yet recruiting, Endeavor Biomedicines, Inc.

P2, N=20, Completed, Endeavor Biomedicines, Inc. | Active, not recruiting --> Completed | N=44 --> 20

P1, N=24, Recruiting, Dwight Owen | Suspended --> Recruiting | Trial completion date: Dec 2026 --> Dec 2027

Vismodegib reversed the promoting effect of ACTR6 on the Hh signaling pathway and stem-related proteins in cells. ACTR6 regulates the molecular basis of stemness maintenance of liver cancer cells through the Hh signaling pathway and promotes the occurrence of liver cancer. This study provides possible targets for the clinical treatment of liver cancer.

P2, N=213, Active, not recruiting, Endeavor Biomedicines, Inc. | Recruiting --> Active, not recruiting

P2, N=12, Recruiting, University of Florida | Suspended --> Recruiting

By comparing treatment and culture context independently, cyclopamine-mediated SHH inhibition and astrocyte-dependent signals use distinct but interacting effects on cell behavior...Astrocyte co-culture significantly modulates the molecular and phenotypic response of GBM cells to SHH inhibition, reshaping apoptotic and proliferative behaviors in both CSCs and bulk populations. These findings highlight the critical importance of the tumor microenvironment in therapeutic response and suggest that effective targeting of SHH signaling may require models that account for astroglial interactions.

Vismodegib may alleviate inflammation and tissue damage in COPD by inhibiting NETs-mediated M1 polarization of macrophages. This study is the first to propose the targeting of NET-driven macrophage polarization via Hedgehog inhibition as a novel therapeutic strategy for COPD, providing a new mechanistic framework for drug repurposing.