cyclopamine

Screening of SAG1.3 derivatives identified compound 11 that competed with BODIPY-cyclopamine binding at different FZDs and inhibited WNT-induced FZD dynamics and β-catenin signaling in HEK293 cells. Furthermore, compound 11 blocked WNT-3A-induced Lgr5 gene expression in human primary hepatocyte spheroids and reduced the viability of RNF43-mutated but not RNF43-wildtype pancreatic cancer cells. Based on our data, we suggest that compound 11 acts on FZDs to limit WNT- and WNT-surrogate-induced receptor dynamics providing a valid proof-of-concept for targeting FZDs with small molecule compounds.

Moreover, both LY294002 and cyclopamine significantly reduced cell proliferation, invasion, and VM formation in vitro and in xenografted OCSCs. HIF-1α knockdown inhibits activation of the PI3K and Hedgehog signaling pathways, thereby reducing EET and VM formation in hypoxia-induced OCSCs.

By comparing treatment and culture context independently, cyclopamine-mediated SHH inhibition and astrocyte-depending 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.

This study highlights the potential of combining Hh inhibitors with trastuzumab as a therapeutic strategy for HER2-positive GC by targeting the AKT/mTOR pathway.

Combination therapies, integrating TRAIL with conventional chemotherapeutics like paclitaxel, cisplatin, and 5-fluorouracil, have shown promise in overcoming resistance by modulating apoptotic pathways and downregulating multidrug resistance genes. Additionally, novel agents like cyclopamine, decitabine, and genistein have emerged as effective TRAIL sensitizers by modulating apoptotic pathways and enhancing DR5 expression...This review emphasizes the need for a comprehensive understanding of the molecular underpinnings of TRAIL resistance and the potential of combination therapies and TRAIL delivery by nanoparticles and oncolytic viruses to enhance treatment outcomes in GC. Future research should focus on elucidating predictive biomarkers and optimizing therapeutic regimens to improve the clinical efficacy of TRAIL-based strategies in GC.

The toxic and adverse effect analysis suggests that alkaloids such as noscapine, lycorine, capsaicin, chelerythrine, caffeine, boldine, and colchicine show favorable therapeutic potential. However, tetrandrine, nitidine, harmine, harmaline, cyclopamine, cocaine, and brucine may pose greater risks than benefits...Overall, while plant alkaloids show promise in glioblastoma therapy, progress in assessing their BBB penetration remains limited. More comprehensive studies integrating glioma research and advanced drug delivery technologies are needed.

Further experiments showed that Cyclopamine (a Shh inhibitor) could significantly inhibit the increase of α-SMA and COL1α1 resulting from HIF-1α but not significantly inhibit HIF-1α induced by CoCl2 in LX-2 cells...In summary, this study demonstrates that the HIF-1α inhibitor AMSP-30m exerts a robust anti-fibrotic effect by inhibiting the Shh pathway, which is identified as a critical underlying mechanism. These findings suggest a promising therapeutic strategy for the treatment of liver fibrosis.

Cyclopamine was used for comparative analysis...The results obtained demonstrate potential of 17β-((3-butylisoxazol-5-yl)methyl)-androst-5-en-3β-ol as the anticancer drug that simultaneously block the Shh signaling pathway and MMP expression. We are confident that the search for substances capable of simultaneously affecting several key components involved in tumor progression is of great importance for the creation of next-generation therapeutic agents.

Furthermore, nine candidate drugs with potential therapeutic efficacy in EC were identified: Bleomycin, Cisplatin, Cyclopamine, PLX4720, Erlotinib, Gefitinib, RO.3306, XMD8.85, and WH.4.023. Furthermore, it identifies potential therapeutic agents with efficacy against EC. These findings hold significant promise for enhancing the survival of EC patients and provide valuable insights to inform clinical decision-making in the management of this disease.

Based on bioinformatics analysis, we discovered a new classification method based on IFN-γ genes, which could divide thyroid cancer patients into three populations with significant characteristics. Different populations had different mutation patterns, immune infiltration levels, and candidate therapeutic drugs.

Patidegib Topical Gel warrants further clinical development.

Among them, N-(4-((dimethylamino)methyl)phenyl)-4-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)benzamide (B31) emerged as the most potent analog following screening with a Gli luciferase reporter assay, competing with cyclopamine in the binding site of Smo protein...Moreover, B31 significantly regressed subcutaneous tumors formed by BxPC-3 cells in nude mice without inducing toxic effects. These results underscore the enhanced efficacy of B31 in the PC model and offer a new avenue for developing effective Hh pathway inhibitors for clinical PC treatment.