Forskolin (Synonyms: 毛喉素; Coleonol; Colforsin)

Forskolin (Coleonol) 是一種有效的腺苷酸環(huán)化酶 (adenylate cyclase) 激huo劑，對(duì)于 I 型腺苷酸環(huán)化酶，IC₅₀ 為 41 nM，EC₅₀ 為 0.5 μM。Forskolin 也是一種細(xì)胞內(nèi) cAMP 形成的誘導(dǎo)劑。Forskolin 誘導(dǎo)多種細(xì)胞類型的分化并激huo孕烷 X 受體 (PXR) 和 FXR。Forskolin 對(duì)心臟產(chǎn)生正性肌力作用，并具有血小板抗凝集和降壓作用。Forskolin 也可誘導(dǎo)細(xì)胞自噬 (autophagy)。

生物活性

Forskolin (Coleonol) is a potent adenylate cyclase activator with an IC₅₀ of 41 nM and an EC₅₀ of 0.5 μM for type I adenylyl cyclase^[1]. Forskolin is also an inducer of intracellular cAMP formation^[2]. Forskolin induces differentiation of various cell types and activates pregnane X receptor (PXR) and FXR^[3]. Forskolin exerts a inotropic effect on the heart, and has platelet antiaggregatory and antihypertensive actions. Forskolin also induces autophagy^[4][5].

IC₅₀ & Target

IC50: 41 nM (Adenylyl cyclase)

EC50: 0.5 μM (Adenylyl cyclase)

體外研究(In Vitro)

Forskolin (Coleonol) is also a potent exosome biogenesis and/or secretion activator in prostate cancer (PC) cells^[8].
Forskolin (Fsk) is a naturally occurring diterpene isolated from Coleus forskholii, directly activates adenylyl cyclase (AC) through its catalytic subunit to increase intracellular levels of cyclic adenosine monophosphate (cAMP)^[1].
Forskolin (Fsk) affects the proliferation of the human T-cell lines such as Kit 225 and MT-2. Forskolin treatment inhibits the proliferation of both Kit 225 and MT-2 cells in a dose-dependent manner with an IC₅₀ equal to ~5 μM Fsk. Forskolin treatment (10-100 μM) increases cAMPi levels ~5- to 20-fold above basal levels, which reache maximum levels between 50-100 μM Forskolin^[6].

體內(nèi)研究(In Vivo)

The Forskolin (Coleonol)-treated Mrp4^-/- mice shows an increased number of Ki67-positive and cleaved caspase 3-positive ECs, a significant decrease in the amount of pericyte coverage, and a reduced number of empty sleeves. In pups exposed to hyperoxia (75% oxygen) from P7 to P12, the Mrp4^-/- mice shows a significant increase in the unvascularized retinal area^[2].
The average blood glucose in the healthy rat group is 102.12±1.94 mg/dL, 101.25±3.56 for control group and 103±2.08 in forskolin group. The data shows that glucose levels at the end of the study are lower in forskolin group, with a significant difference according to the statistical tests applied (p=0.03)^[7].

分子量：410.50

Formula：C₂₂H₃₄O₇

_{CAS 號(hào)：66575-29-9}

中文名稱：毛喉素

運(yùn)輸條件：Room temperature in continental US; may vary elsewhere.

儲(chǔ)存方式：

4°C, protect from light

*In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)

溶解性數(shù)據(jù)

In Vitro: 

參考文獻(xiàn)

[1]. Robbins JD, et al. Forskolin carbamates: binding and activation studies with type I adenylyl cyclase. J Med Chem. 1996 Jul 5;39(14):2745-52.

[2]. Matsumiya W, et al. Forskolin modifies retinal vascular development in Mrp4-knockout mice. Invest Ophthalmol Vis Sci. 2012 Dec 7;53(13):8029-35.

[3]. Mayati A, et al. Functional polarization of human hepatoma HepaRG cells in response to forskolin. Sci Rep. 2018 Oct 31;8(1):16115.

[4]. Awad JA, et al. Interactions of forskolin and adenylate cyclase. Effects on substrate kinetics and protection against inactivation by heat and N-ethylmaleimide. J Biol Chem. 1983 Mar 10;258(5):2960-5.

[5]. Seamon KB, et al. Structure-activity relationships for activation of adenylate cyclase by the diterpene forskolin and its derivatives. J Med Chem. 1983 Mar;26(3):436-9.

[6]. Ríos-Silva M, et al. Effect of chronic administration of forskolin on glycemia and oxidative stress in rats with and without experimental diabetes. Int J Med Sci. 2014 Mar 11;11(5):448-52.

[7]. Rodriguez G, et al. Forskolin-inducible cAMP pathway negatively regulates T-cell proliferation by uncoupling the interleukin-2 receptor complex. J Biol Chem. 2013 Mar 8;288(10):7137-46.

[8]. Amrita Datta, et al. High-throughput screening identified selective inhibitors of exosome biogenesis and secretion: A drug repurposing strategy for advanced cancer. Sci Rep. 2018 May 25;8(1):8161.