KCN1, a novel synthetic sulfonamide, is a HIF pathway inhibitor with potential anticancer activity in vitro and in vivo anti-pancreatic cancer activities and preclinical pharmacology. KCN1 specifically inhibited HIF reporter gene activity in several glioma cell lines at the nanomolar level. KCN1 also downregulated transcription of endogenous HIF-1 target genes, such as VEGF, Glut-1, and carbonic anhydrase 9, in a hypoxia-responsive element (HRE)-dependent manner. KCN1 potently inhibited the growth of subcutaneous malignant glioma tumor xenografts with minimal adverse effects on the host. Mechanistically, KCN1 did not downregulate the levels of HIF-1α or other components of the HIF transcriptional complex; rather, it antagonized hypoxia-inducible transcription by disrupting the interaction of HIF-1α with transcriptional coactivators p300/CBP.CONCLUSIONS: The new HIF pathway inhibitor KCN1 has antitumor activity in mouse models, supporting its further translation for the treatment of human tumors displaying hypoxia or HIF overexpression (source: Clin Cancer Res. 2012 Nov 21. [Epub ahead of print] )

MedKoo Cat#: 401515 Name: KCN1 CAS#: 927823-01-6 Chemical Formula: C26H27NO5S Exact Mass: 465.16099 Molecular Weight: 465.56 Elemental Analysis: C, 67.08; H, 5.85; N, 3.01; O, 17.18; S, 6.89

Synonym: KCN1; KCN-1; KCN 1.

IUPAC/Chemical Name: 3,4-dimethoxy-N-[(2,2-dimethyl-2H-chromen-6-yl)methyl]-N-phenylbenzenesulfonamide

InChi Key: IPZJNJPAVPZHJM-UHFFFAOYSA-N

InChi Code: InChI=1S/C26H27NO5S/c1-26(2)15-14-20-16-19(10-12-23(20)32-26)18-27(21-8-6-5-7-9-21)33(28,29)22-11-13-24(30-3)25(17-22)31-4/h5-17H,18H2,1-4H3

SMILES Code: O=S(C1=CC=C(OC)C(OC)=C1)(N(CC2=CC(C=CC(C)(C)O3)=C3C=C2)C4=CC=CC=C4)=O

Technical Data

Appearance: Solid powder

Purity: >98%

Shipping Condition: 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.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >5 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

Harmonized System Code: 293490

Additional Information

    The following data was from PLoS One . 2012;7(9):e44883. doi: 10.1371/journal.pone.0044883. Epub 2012 Sep 13.            Figure 1. In vitro anticancer activities of KCN1 against pancreatic cancer cells.  (B) Cell growth inhibitory activity of KCN1 in human pancreatic cancer cells. Cells were exposed to various concentrations of KCN1 for 72 h, followed by an MTT assay. ( Source: PLoS One . 2012;7(9):e44883. doi: 10.1371/journal.pone.0044883. Epub 2012 Sep 13. ) Figure 1. In vitro anticancer activities of KCN1 against pancreatic cancer cells.  (B) Cell growth inhibitory activity of KCN1 in human pancreatic cancer cells. Cells were exposed to various concentrations of KCN1 for 72 h, followed by an MTT assay. ( )                    

References

1: Wang W, Ao L, Rayburn ER, Xu H, Zhang X, Zhang X, Nag SA, Wu X, Wang MH, Wang H, Van Meir EG, Zhang R. KCN1, a novel synthetic sulfonamide anticancer agent: in vitro and in vivo anti-pancreatic cancer activities and preclinical pharmacology. PLoS One. 2012;7(9):e44883. doi: 10.1371/journal.pone.0044883. Epub 2012 Sep 13. PubMed PMID: 23028659; PubMed Central PMCID: PMC3441526.

2: Yin S, Kaluz S, Devi NS, Jabbar AA, de Noronha RG, Mun J, Zhang Z, Boreddy PR, Wang W, Wang Z, Abbruscato T, Chen Z, Olson JJ, Zhang R, Goodman MM, Nicolaou KC, Van Meir EG. Arylsulfonamide KCN1 Inhibits In Vivo Glioma Growth and Interferes with HIF Signaling by Disrupting HIF-1α Interaction with Cofactors p300/CBP. Clin Cancer Res. 2012 Nov 21. [Epub ahead of print] PubMed PMID: 22923450; PubMed Central PMCID: PMC3518680.      

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