C188-9

• CAS: 432001-19-9
• Catalog Number: ACM432001199
• Category: Inhibitors
• Molecular Weight: 471.52
• Molecular Formula: C27H21NO5S
• 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.
• Synonyms: C188-9; C 188-9; C-188-9; C-1889; C1889; C 1889; C-1889; F0808-0084
• IUPAC Name: N-(1',2-dihydroxy-[1,2'-binaphthalen]-4'-yl)-4-methoxybenzenesulfonamide
• Canonical SMILES: O=S(C1=CC=C(OC)C=C1)(NC2=C3C=CC=CC3=C(O)C(C4=C5C=CC=CC5=CC=C4O)=C2)=O
• InChI: InChI=1S/C27H21NO5S/c1-33-18-11-13-19(14-12-18)34(31,32)28-24-16-23(27(30)22-9-5-4-8-21(22)24)26-20-7-3-2-6-17(20)10-15-25(26)29/h2-16,28-30H,1H3
• InChI Key: QDCJDYWGYVPBDO-UHFFFAOYSA-N
• Solubility: Soluble in DMSO
• Appearance: Pinky beige solid powder
• Shelf Life: >2 years if stored properly
• Storage: Dry, dark and at 0-4 °C for short term (days to weeks) or -20 °C for long term (months to years).
• Biological Target: C188-9 is a STAT3 inhibitor, with a Kd of 4.7 nM. C188-9 inhibits G-CSF-induced STAT3 activation and STAT3-dependent gene expression.
• Drug Formulation: This drug may be formulated in DMSO
• Elemental Analysis: C, 68.78; H, 4.49; N, 2.97; O, 16.97; S, 6.80
• Exact Mass: 471.114
• HS Tariff Code: 2934.99.9001
• In Vitro Activity: To evaluate the effect of C188-9 on the expression of target genes that are up-regulated by Stat3, AML cell lines were pretreated with 10μM C188-9 for 1 hour, then stimulated with G-CSF (100 ng/mL) for 1 hour, and total RNA was extracted for quantitative RT-PCR. The SOCS3 gene is a Stat3 target gene that encodes the Jak inhibitory protein SOCS3. PIM1 encodes the kinase Pim1, an oncogene implicated in several cancers, including AML,15 which is also an accepted target gene of Stat3.16 The mRNA levels for these transcripts were up-regulated in AML cells on G-CSF treatment, and the increase was reduced in cells that were pretreated with C188-9 (Figure 4A). In contrast, C188-9 did not significantly affect the level of the ATRA-inducible transcript CCL2417 in NB-4 cells stimulated with ATRA. The smaller effect of C188-9 on PIM1 mRNA in Kasumi-1 cells was possibly the result of ERK and/or Akt pathways up-regulating this gene, as has been described.18 Indeed, Figure 3E shows that ERK1/2 and Akt were dramatically activated in Kasumi-1 cells by G-CSF and not inhibited by C188-9. These studies confirm that C188-9 not only inhibited Stat3 activation, it also inhibited Stat3-dependent gene transcription.; Reference: Blood. 2011 May 26;117(21):5701-9. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21447830/
• In Vivo Activity: 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.; Reference: Oncotarget. 2016 May 3;7(18):26307-30. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/27027445/
• Shipping: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
• Stock Solution Storage: 0-4 °C for short term (days to weeks), or -20 °C for long term (months).