SNX-7081

SNX-7081 is an Hsp90 inhibitor with K_i and IC₅₀ values of 26 nM and 44 nM, respectively. SNX-7081 blocks the nuclear translocation of NF-κB, inhibits the production of pro-inflammatory cytokines, attenuates the ERK/JNK and PDGF signaling pathways, and suppresses LPS (HY-D1056)-induced nitric oxide production. SNX-7081 inhibits DNA repair, induces G₂/M cell cycle arrest, and triggers apoptosis via downregulation of MYC/nucleolin and activation of Fas. SNX-7081 can be used in research related to rheumatoid arthritis and cancer^[1][2][3]. In Vitro:SNX-7081 (0.0001-10 μM; 6-24 h) inhibits the nuclear translocation of NF-κB, with an IC₅₀ value of 114 nM in IL-1β-stimulated human umbilical vein endothelial cells, 241 nM in LPS-stimulated J774 mouse macrophages, 44 nM in IL-1β-stimulated rheumatoid arthritis synovial fibroblasts, and 88 nM in TNF-α-stimulated rheumatoid arthritis synovial fibroblasts^[1].
SNX-7081 (6-24 h) potently suppresses the production of multiple proinflammatory cytokines in THP-1 human monocytes, human umbilical vein endothelial cells, and rheumatoid arthritis synovial fibroblasts, with an IC₅₀ value as low as 13 nM; it also inhibits the proliferation of activated human umbilical vein endothelial cells with an IC₅₀ of 3 nM, while exerting minimal effects on the proliferation of rheumatoid arthritis synovial fibroblasts^[1].
SNX-7081 (0.001-10 μM; 24 h) inhibits growth factor-induced ERK-1/2 signaling pathway in human umbilical vein endothelial cells with an IC₅₀ of 11 nM; inhibits IL-1β-induced JNK signaling pathway in human umbilical vein endothelial cells with an IC₅₀ of 94 nM; inhibits PDGF-induced global tyrosine signaling pathway in NIH3T3 mouse fibroblasts with an IC₅₀ of 56 nM; and also inhibits PDGF-induced ERK-1/2 signaling pathway in NIH3T3 mouse fibroblasts with an IC₅₀ of 14 nM^[1].
SNX-7081 (0.001-10 μM; 6 h) inhibits lipopolysaccharide (LPS)-induced nitric oxide production in J774 murine macrophages, with an IC₅₀ of 6 nM^[1].
SNX-7081 (100 nM; 48 h) induces extensive changes in protein expression in MEC1 cells, including significant downregulation of DNA replication and repair proteins, as well as upregulation of proteins related to energy metabolism and protein metabolism^[2].
SNX-7081 (100 nM; 48 h) alters the levels of key regulatory proteins in MEC1 cells, including decreased expression of NFκB2 p52, MYC and BRCA1^[2].
SNX-7081 (100 nM; 48 h) induces a slight increase in the DNA damage marker γH2AX in p53-mutant MEC1, MEC2 and U266 B-lymphoma cells^[2].
SNX-7081 (100 nM; 48 h) induces extensive changes in protein expression in MEC1 cells, including upregulation of proteins related to DNA damage, epigenetic regulation and pro-apoptosis, as well as downregulation of proteins related to DNA replication and repair^[2].
SNX-7081 (100 nM; 48 h) alters the levels of key regulatory proteins in MEC1 cells, including decreased expression of MYC, CCND1 and BRCA1^[2].
SNX-7081 (100 nM; 48 h) synergistically increases the expression level of the DNA damage marker γH2AX in p53-mutated MEC1, MEC2 and U266 B-lymphocyte cancer cells^[2].
SNX-7081 (72 h) potently inhibits the growth of human cancer cell lines including K562, A375, MCF-7, Hep-2, HepG2, A549, SW-620 and HeLa, with a mean IC₅₀ of approximately 1 μM, while exhibits low cytotoxicity against human normal cell lines L-02, HDF and MRC5^[3].
SNX-7081 (1 μM; 48 h) induces G₂/M cell cycle arrest in K562, Hep-2, A549, SW-620 and HeLa human cancer cells, and exhibits stronger activity than SNX-2112 in K562, Hep-2 and A549 cells^[3].
SNX-7081 (1 μM; 48 h) induces apoptosis in K562, A375, Hep-2, A549, SW-620 and HeLa human cancer cells, and exhibits stronger activity against K562, Hep-2 and A549 cells than SNX-2112^[3].
SNX-7081 (1 μM; 0-48 h) reduces the expression of Hsp90 client proteins IKKα, CHK1, GSK3 and Raf-1 in human leukemia K562 cells in a time-dependent manner, and is more potent than SNX-2112^[3].