C188-9

SKU: orb1222264

Description

C188-9 is a STAT3 inhibitor. HDM-induced airway inflammation, remodeling, and Th2/Th17-type cell accumulation involve STAT3 activation that can be prevented by C188-9 treatment. STAT3 inhibition with C188-9 resulted in attenuated skin fibrosis, myofibroblast accumulation, pro-fibrotic gene expression and collagen deposition in both mouse models of skin fibrosis. C188-9 decreased in vitro dermal fibroblast production of fibrotic genes induced by IL-6 trans-signalling and TGF-β. Finally, TGF-β induced phosphotyrosylation of STAT3 in a SMAD3-dependent manner.(In Vitro):C188-9 is a Stat3 inhibitor, with a Kd of 4.7 nM. The IC50s of C188-9 to inhibit Stat3 activation in AML cell lines are in the range of 4-7 μM, and in primary AML samples the IC50s are in the range of 8-18 μM. For apoptosis studies, AML cell lines and primary samples are treated for 24 hours with C188-9, then apoptotic cells are quantified by FACS analysis for annexin V-labeled cells. The EC50s for apoptosis induction are quite variable, ranging from 6 μM to over 50 μM.(In Vivo):Of the approximately 13,528 discernible genes, levels of 37 gene transcripts are altered by C188 (17 down and 20 up-regulated, fdr <0.01, fold change≥1.5), of which 7 are known STAT3 gene targets. In comparison, C188-9 affects a much greater number of genes involved in oncogenesis (384 total, 95 down- and 289 up-regulated), including 76 genes previously reported as regulated by STAT3 (38 down-regulated and 38 up-regulated). Among the 38 genes previously shown to be upregulated by STAT3, 24 (63%) genes are downregulated by C188-9 treatment, as expected. Additionally, 10 more genes downregulated by C188-9 (fdr <0.01, fold change≥1.5) that previously are shown to be upregulated by STAT1. Thus, 40 of 48 (83.3%) genes downregulated by C188-9 previously are shown to be positively regulated by STAT1, including sixteen genes shown to be co-regulated by STAT3 and STAT1. This analysis raises the possibility that the effect of C188-9 on gene transcript levels in HNSCC tumors is mediated by its effects on both STAT3 and STAT1.

Key Properties

• CAS Number: 432001-19-9
• MW: 471.52
• Purity: >98% (HPLC)
• Formula: C₂₇H₂₁NO₅S
• SMILES: O=S(=O)(Nc4cc(c1c2ccccc2ccc1O)c(O)c3ccccc34)c5ccc(OC)cc5
• Target: STAT3
• Solubility: DMSO : ≥ 62 mg/mL; 131.49 mM

Bioactivity

• In Vivo:
  Of the approximately 13, 528 discernible genes, levels of 37 gene transcripts are altered by C188 (17 down and 20 up-regulated, fdr <0.01, fold change≥1.5), of which 7 are known STAT3 gene targets. In comparison, C188-9 affects a much greater number of genes involved in oncogenesis (384 total, 95 down-and 289 up-regulated), including 76 genes previously reported as regulated by STAT3 (38 down-regulated and 38 up-regulated). Among the 38 genes previously shown to be upregulated by STAT3, 24 (63%) genes are downregulated by C188-9 treatment, as expected. Additionally, 10 more genes downregulated by C188-9 (fdr <0.01, fold change≥1.5) that previously are shown to be upregulated by STAT1. Thus, 40 of 48 (83.3%) genes downregulated by C188-9 previously are shown to be positively regulated by STAT1, including sixteen genes shown to be co-regulated by STAT3 and STAT1. This analysis raises the possibility that the effect of C188-9 on gene transcript levels in HNSCC tumors is mediated by its effects on both STAT3 and STAT1.
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• In Vitro:
  C188-9 is a Stat3 inhibitor, with a Kd of 4.7 nM. The IC50s of C188-9 to inhibit Stat3 activation in AML cell lines are in the range of 4-7 μM, and in primary AML samples the IC50s are in the range of 8-18 μM. For apoptosis studies, AML cell lines and primary samples are treated for 24 hours with C188-9, then apoptotic cells are quantified by FACS analysis for annexin V-labeled cells. The EC50s for apoptosis induction are quite variable, ranging from 6 μM to over 50 μM.
  Read more...

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

C188-9 | C 188-9 | C-188-9

Quick Database Links

Gene Symbol

STAT3