KM 11060

KM11060 is a mutated F508del cystic fibrosis transmembrane conductance regulator (CFTR) corrector. The most common mutation (~90%) in the CFTR gene is a deletion of phenylalanine 508 (F508del). KM11060 is an analog of sildenafil, which restores a function of the F508del mutated CFTR chloride channel. KM11060 appears to be more potent than sildenafil, forskolin, and genistein.

Product information

CAS Number: 774549-97-2

Molecular Weight: 422.33

Formula: C19H17Cl2N3O2S

Synonym:

KM11060

KM-11060

KM 11060

Chemical Name: 7-chloro-4-(4-((4-chlorophenyl)sulfonyl)piperazin-1-yl)quinoline

Smiles: O=S(=O)(C1C=CC(Cl)=CC=1)N1CCN(CC1)C1=CC=NC2=CC(Cl)=CC=C12

InChiKey: GIEHIZKCIZLXLF-UHFFFAOYSA-N

InChi: InChI=1S/C19H17Cl2N3O2S/c20-14-1-4-16(5-2-14)27(25,26)24-11-9-23(10-12-24)19-7-8-22-18-13-15(21)3-6-17(18)19/h1-8,13H,9-12H2

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO, not in water

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

Small-molecule correctors such as KM11060 may serve as useful pharmacological tools in studies of the F508del-CFTR processing defect and in the development of cystic fibrosis therapeutics. KM11060 rescues F508del-CFTR trafficking in cultured cells and native epithelial tissues. KM11060 partially corrects F508del-CFTR processing and increases surface expression to 75% of that observed in cells incubated at low temperature. Up to 50% of the F508del-CFTR in cells treated with KM11060 was complex-glycosylated, indicating passage through the Golgi. KM11060 as a promising compound for further development of CF therapeutics.

In Vivo:

In LPS-induced acute lung inflammation, blockade of PSGL-1 (P-selectin glycoprotein ligand-1) or P-selectin, antagonism of PAF by WEB2086, or correction of mutated CFTR trafficking by KM11060 could significantly increase plasma lipoxin A4 levels in F508del relevant to wildtype mice.

References:

1. Wu H, Yang J, Su EM, Li L, Zhao C, Yang X, Gao Z, Pan M, Sun P, Sun W, Jiang Y, Su X. Lipoxin A4 and platelet activating factor are involved in E. coli or LPS-induced lung inflammation in CFTR-deficient mice. PLoS One. 2014 Mar 26;9(3):e93003. doi: 10.1371/journal.pone.0093003. eCollection 2014. PubMedPMID: 24671173; PubMed Central PMCID: PMC3966846.
2. Loo TW, Bartlett MC, Shi L, Clarke DM. Corrector-mediated rescue of misprocessed CFTR mutants can be reduced by the P-glycoprotein drug pump. Biochem Pharmacol. 2012 Feb 1;83(3):345-54. doi: 10.1016/j.bcp.2011.11.014. Epub 2011 Nov 28. PubMed PMID: 22138447.
3. Robert R, Carlile GW, Pavel C, Liu N, Anjos SM, Liao J, Luo Y, Zhang D, Thomas DY, Hanrahan JW. Structural analog of sildenafil identified as a novel corrector of the F508del-CFTR trafficking defect. Mol Pharmacol. 2008 Feb;73(2):478-89. Epub 2007 Nov 1. PubMed PMID: 17975008.

Products are for research use only. Not for human use.