CFTR Inhibitor-172

• CAT Number: I003087
• CAS Number: 307510-92-5
• Molecular Formula: C₁₈H₁₀F₃NO₃S₂
• Molecular Weight: 409.4
• Purity: ≥95%
• Target: CFTR
• Solubility: 10 mM in DMSO
• Storage: Store at -20C
• IC50: 300 nM (Ki) [1]
• InChI: InChI=1S/C18H10F3NO3S2/c19-18(20,21)12-2-1-3-13(9-12)22-15(23)14(27-17(22)26)8-10-4-6-11(7-5-10)16(24)25/h1-9H,(H,24,25)/b14-8-
• InChIKey: JIMHYXZZCWVCMI-ZSOIEALJSA-N
• SMILES: C1=CC(=CC(=C1)N2C(=O)C(=CC3=CC=C(C=C3)C(=O)O)SC2=S)C(F)(F)F

CFTR(inh)-172 is an reversibly inhibitor of CFTR short-circuit current in less than 2 minutes in a voltage-independent manner with Ki approximately 300 nM.IC50 value: 300 nM (Ki) [1]Target: CFTRin vitro: CFTR(inh)-172 was nontoxic at high concentrations in cell culture and mouse models. At concentrations fully inhibiting CFTR, CFTR(inh)-172 did not prevent elevation of cellular cAMP or inhibit non-CFTR Cl(-) channels, multidrug resistance protein-1 (MDR-1), ATP-sensitive K(+) channels, or a series of other transporters [1]. Short-circuit current experiments indicated similar CFTR(inh)-172 inhibitory potency (K(i) approximately 0.5 microM) for inhibition of Cl(-) current in wild-type, G551D, and G1349D CFTR; however, K(i) was significantly reduced to 0.2 microM for DeltaF508 CFTR [2].in vivo: A single intraperitoneal injection of CFTR(inh)-172 (250 micro g/kg) in mice reduced by more than 90% cholera toxin-induced fluid secretion in the small intestine over 6 hours [1].

Reference

[1]. Ma T, et al. Thiazolidinone CFTR inhibitor identified by high-throughput screening blocks cholera toxin-induced intestinal fluid secretion. J Clin Invest. 2002 Dec;110(11):1651-8.
[2]. Taddei A, et al. Altered channel gating mechanism for CFTR inhibition by a high-affinity thiazolidinone blocker. FEBS Lett. 2004 Jan 30;558(1-3):52-6.