SNX-2112

In a TNBC xenograft model, 13b significantly reduced tumor volume and weight with a better safety profile than 5-fluorouracil. Molecular docking studies showed that 13b binds within the Hsp90 ATP-binding pocket in a comparable pattern to the known inhibitors, SNX-2112 and GDM. These findings support 13b as a promising and well-tolerated Hsp90-targeted anticancer lead, especially for the treatment of breast cancer.

We demonstrated that combining selumetinib and SNX-2112 or retaspimycin can achieve better tumor inhibition with synergistic effects. The combination significantly delays the progression of mouse pNFs. The combination of selumetinib and HSP90i has significant synergistic effects, provides therapeutic inhibitor effects, and reduces the selumetinib dosage in combination.

ImmuProgML offers a promising avenue for understanding the intricate relationship between tumors and the immune system, providing a machine learning framework for personalized cancer immunotherapy selections.

W-H4 emerges as a potential Hsp90 inhibitor, providing novel therapeutic opportunities for the targeted treatment of acute myeloid leukemia.

Consequently, the combined therapy enhanced by inhibiting HSP90-HIF1α effectively suppresses tumor growth via synergistic effects, with high photothermal conversion and ROS productivity under mild temperature (42 °C). Furthermore, using SNX2112 improves the efficacy of the combined photothermal and photodynamic therapy, showing its eminent potential in TNBC treatment.

Drug sensitivity analysis identified specific drugs, including PAC-1, SNX-2112, BELINOSTAT, VORINOSTAT, TPCA-1, and PHA-893,888, whose efficacy may be influenced by PTPN6 expression. Knocking down PTPN6 expression inhibited the proliferation and migration of colorectal cancer cells in vitro, confirming its oncogenic role in this cancer type. This pan-cancer analysis establishes PTPN6's multifaceted influence on tumor immunity and its potential as a biomarker and therapeutic target.

Targeting the ITG-COL network is a promising approach to the treatment of melanoma.

These results demonstrate that HSP90 inhibition is associated with potent activity in PRCC, and implicate the PI3K/AKT and MEK/ERK1/2 pathways as important mediators of tumorigenesis. These data also provide the impetus for further clinical evaluation of HSP90, AKT, MEK or E2F pathway inhibitors in PRCC.

We observed that KMT2A-r cell lines were more sensitive to 5-Fluorouracil (5FU), Gemcitabine (both antimetabolite chemotherapy drugs), WHI-P97 (JAK-3 inhibitor), Foretinib (MET/VEGFR inhibitor), SNX-2112 (Hsp90 inhibitor), AZD6482 (PI3Kβ inhibitor), KU-60019 (ATM kinase inhibitor), and Pevonedistat (NEDD8-activating enzyme (NAE) inhibitor). Moreover, IC50 data from analyses of ex-vivo drug sensitivity to small-molecule inhibitors reveals that Foretinib is a promising drug option for AML patients carrying FLT3 activating mutations. Thus, we provide novel and accurate options for the diagnostic screening and therapy of KMT2A-r leukemia, regardless of leukemia subtype.

We found that CSGPI might serve as an effective biomarker predicting metastasis probability and radioresistance for PCa and proposed that immune evasion was involved in the process of PCa metastasis.

In conclusion, the current study is the first to discover the mechanism of SNX-2112 in NSCLC. SNX-2112 induced apoptosis and also inhibited the proliferation, invasion, and migration of NSCLC cells by downregulating EMT via the Wnt/β-catenin signaling pathway.

Based on the complex crystal structure and molecular interaction analysis, 32 novel SNX-2112 derivatives were designed, and 25 new ones displayed increased binding force with the target Hsp90 verified by molecular docking evaluation. The results would provide new references and guides for anti-NSCLC new drug development based on the lead compound SNX-2112.