NKH 477 is a novel water-soluble forskolin derivative [1]. NKH 477 upregulates cAMP by activating adenylate cyclase, which is used to enhance myocardial contraction and dilate blood vessels [2]. NKH 477 is often used in the research and treatment of cardiovascular diseases such as heart failure [3-4].
In MCF7, HT29, A431, WiDr, RKO, A375, H630, Du145, SW480, and SW620 cells, NKH 477 (100μM; 48h) inhibits the proliferation of cancer cell lines [5]. In endothelial cells, NKH477 (0.1-1.0μM; 1h) increases cAMP in a concentration-dependent manner [2]. In CellSensorTM CRE-bla CHO-K1 cells, NKH 477 (30nM; 5h) induces CRE-conjugated β-lactamase activity in a concentration-dependent manner [6]. In endothelial cells, NKH477 (0.01-0.3μM; 1h) attenuated the phasic and the tonic increases in both [Ca2+]i and force induced by 10μM noradrenaline, in a concentration-dependent manner [7].
In specific pathogen-free Lewis rats and brown-norway rats, NKH 477 (1, 2, 3mg/kg; po; 10d) significantly prolonged allograft survival and reduced histopathological rejection in a dose-dependent manner [8]. In sprague-dawley rats, acute or chronic administration of NKH 477 (1.5mg/kg, ip, 9d) to rats significantly reduced their locomotion and upright behavior [9].
References:
[1]. Hosono M, Takahira T, Fujita A, et al. Cardiovascular and adenylate cyclase stimulant properties of NKH477, a novel water-soluble forskolin derivative. Journal of cardiovascular pharmacology. 1992 Apr 1; 19(4): 625-634.
[2]. Shafiq J, Suzuki S, Itoh T, Kuriyama H. Mechanisms of vasodilation induced by NKH477, a water-soluble forskolin derivative, in smooth muscle of the porcine coronary artery. Circulation research. 1992 Jul; 71(1): 70-81.
[3]. Fujita A, Takahira T, Hosono M, et al. Improvement of drug-induced cardiac failure by NKH477, a novel forskolin derivative, in the dog heart-lung preparation. The Japanese Journal of Pharmacology. 1992;58(4):375-381.
[4]. Hosoda S, Motomiya T, Katagiri T, et al. Acute Effect of NKH477, a Novel Forskolin Derivative, in Patients with Acute Heart Failure A Multicenter Placebo-Controlled Double-Blind Trial. Rinsho yakuri/Japanese Journal of Clinical Pharmacology and Therapeutics. 1997 Jun 30; 28(2): 583-602.
[5]. Faris Q. Alenzi, Mohamed L. Salem, Waleed G, et al. NKH477 inhibits proliferation and induces apoptosis in a panel of cancer cell lines. Journal of Personalized Medicine. 2010; 24(03): 182-187.
[6]. Xia M, Guo V, Huang R, et al. A cell-based β-lactamase reporter gene assay for the CREB signaling pathway. Current chemical genomics. 2009 Mar 17; 3: 7.
[7]. Ito S, Suzuki S, Itoh T. Effects of a water‐soluble forskolin derivative (NKH477) and a membrane‐permeable cyclic AMP analogue on noradrenaline‐induced Ca2+ mobilization in smooth muscle of rabbit mesenteric artery. British journal of pharmacology. 1993 Nov; 110(3): 1117-1125.
[8]. Nakashima S, Morikawa M, Komatsu K, et al. Antiproliferative effects of NKH477, a forskolin derivative, on cytokine profile in rat lung allografts. The Journal of heart and lung transplantation. 2005 Apr 1; 24(4): 462-469.
[9]. Kofman O, Bersudsky Y. Behavioural effects of NKH-477, a forskolin analogue, on locomotion and rearing in rats. International Journal of Neuropsychopharmacology. 2000 Mar 1; 3(1): 27-33.
NKH 477是一种新型水溶性毛喉素衍生物 [1]。NKH 477通过激活腺苷酸环化酶来上调cAMP水平，而腺苷酸环化酶具有增强心肌收缩和扩张血管的作用 [2]。NKH 477常用于研究和治疗心力衰竭等心血管疾病 [3-4]。
在MCF7、HT29、A431、WiDr、RKO、A375、H630、Du145、SW480和SW620细胞中，NKH 477（100μM；48h）可抑制癌细胞系的增殖 [5]。在内皮细胞中，NKH477（0.1-1.0μM；1h）以浓度依赖性方式增加cAMP [2]。在CellSensorTM CRE-bla CHO-K1细胞中，NKH 477（30nM；5h）以浓度依赖性方式诱导CRE结合的β-内酰胺酶活性 [6]。在内皮细胞中，NKH477（0.01-0.3μM；1h）以浓度依赖性方式减弱10μM去甲肾上腺素引起的[Ca2+]i和力的阶段性和强直性增加 [7]。
在无特定病原体的Lewis大鼠和Brown-Norway大鼠中，NKH 477（1、2、3mg/kg；po；10d）显著延长同种异体移植物的存活率，并以剂量依赖性方式减少组织病理学排斥反应 [8]。在Sprague-Dawley大鼠中，急性或慢性给予NKH 477（1.5mg/kg，ip，9d）显著降低其运动和直立行为 [9]。