GlyH-101 是一种有效的 CFTR 抑制剂。
| Cas No. | 328541-79-3 |
| 化学名 | N'-[(3,5-dibromo-4-hydroxy-6-oxocyclohexa-2,4-dien-1-ylidene)methyl]-2-(naphthalen-2-ylamino)acetohydrazide |
| Canonical SMILES | C1=CC=C2C=C(C=CC2=C1)NCC(=O)NNC=C3C=C(C(=C(C3=O)Br)O)Br |
| 分子式 | C19H15Br2N3O3 |
| 分子量 | 493.15 |
| 溶解度 | ≥ 20.35mg/mL in DMSO |
| 储存条件 | Store at -20°C |
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while. |
| Shipping Condition | Evaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request |
| 产品描述 | GlyH-101 is a cell-permeable glycinyl hydrazone compound that blocks CFTR with Ki of 1.4 uM.IC50 value: 1.4 uM (Ki, at +60 mV) [1]Target: CFTRin vitro: GlyH-101 reversibly inhibited CFTR Cl- conductance in<1 min. Whole-cell current measurements revealed voltage-dependent CFTR block by GlyH-101 with strong inward rectification, producing an increase in apparent inhibitory constant Ki from 1.4 microM at +60 mV to 5.6 microM at -60 mV. GlyH-101 inhibitory potency was independent of pH from 6.5-8.0, where it exists predominantly as a monovalent anion with solubility approximately 1 mM in water[1]. In HeLa cells, these events were associated with a decrease in the rate of oxygen consumption, with GlyH-101 demonstrating a higher potency than CFTR(inh)-172. The impact of CFTR inhibitors on inflammatory parameters was also tested in HeLa cells. CFTR(inh)-172, but not GlyH-101, induced nuclear translocation of nuclear factor-kappaB (NF-kappaB) [2]. GlyH-101 is a glycine hydrazide that has recently been shown to block CFTR channels but its effects on cardiomyocytes are unknown. Here the action of GlyH-101 on cardiac I(Cl.PKA) and on other ion currents has been established. Whole-cell patch-clamp recordings were made from rabbit isolated ventricular myocytes. GlyH-101 blocked I(Cl.PKA) in a concentration- and voltage-dependent fashion (IC(50) at +100 mV=0.3 ± 1.5 μM and at -100 mV=5.1 ± 1.3 μM) [3].in vivo: Topical GlyH-101 (10 microM) in mice rapidly and reversibly inhibited forskolin-induced hyperpolarization in nasal potential differences. In a closed-loop model of cholera, intraluminal GlyH-101 (2.5 microg) reduced by approximately 80% cholera toxin-induced intestinal fluid secretion [1]. References:
[1]. Muanprasat C, et al. Discovery of glycine hydrazide pore-occluding CFTR inhibitors: mechanism, structure-activity analysis, and in vivo efficacy. J Gen Physiol. 2004 Aug;124(2):125-37.
[2]. Kelly M, et al. Cystic fibrosis transmembrane regulator inhibitors CFTR(inh)-172 and GlyH-101 target mitochondrial functions, independently of chloride channel inhibition. J Pharmacol Exp Ther. 2010 Apr;333(1):60-9.
[3]. Barman PP, et al. Cardiac ion channel current modulation by the CFTR inhibitor GlyH-101. Biochem Biophys Res Commun. 2011 Apr 29;408(1):12-7. |
