Activators & Inhibitors

Quercetin is an inhibitor of PDEs of both cAMP and cGMP. It is a flavonoid found in plant and fruit bark or rinds. It is estimated that normal dietary intake of Quercetin for humans is 0.1-0.2 mg/kg. Quercetin can induce renal adenomas in male rats when fed at 2,000 mg/kg.

BAY-60-7550 is a potent inhibitor of PDE2. It is more selective for PDE2 than PDE1 by 50-fold. Similarly, it is 100-fold more selective for PDE4B, PDE5B, PDE7B, PDE8A, PDE9A, PDE10A, and PDE11A.

Milrinone, also known as WIN 47203 and Primacor®, is an inhibitor of PDE3. It is less effective against other PDE isoforms. Milrinone has positive inotropic and vasodilatory effects in vivo.

Icariin is a PDE5 inhibitor. It is the active component of the Chinese medicinal plant E. brevicornum. It can induce differentiation of cardiomyocytes and upregulates the expression of cardiac genes. Icariin increase the proliferation and differentiation of cultured human osteoblasts, which appears to be mediated in part by upregulating bone morphogenetic protein 2 mRNA.

Zaprinast is a cGMP-specific PDE inhibitor which moderately inhibits PDE5 and PDE6. It weakly inhibits PDE9, PDE10 and PDE11. Sildenafil (Viagra™) was developed from Zaprinast, which enhances the vasodilatory effects of nitric oxide in a range of vascular tissues by prolonging the cGMP-mediated activation of cGMP-dependent protein kinase. Also, GPR35 is activated by Zaprinast.

Ellagic acid, also known as TBBD, Gallogen, and Lagistase, can alter cytochrome P450 activity, and improve metabolism and clearance of xenobiotics, as well as alter immune function. It can also block methylation of arginine 17 of histone 3 (H3R17) by coactivator-associated arginine methyltransferase 1 (CARM1), or PRMT4, without significantly altering histone acetylase or DNA methyltransferase activity.

BIX01294 (hydrochloride hydrate) is a selective inhibitor of G9a, a histone methyltransferase (HMT). It can also inhibit G9a-like protein (GLP), but is less effective. There are no known inhibitory effects on other HMTs. Also, BIX01294 has been used in combination with Bay-K8644 to facilitate generation of induced pluripotent stem cells from somatic cells in vitro.

Chaetocin is an inhibitor of histone methyltransferases (HMTs) including SUV39H1 and Lys9-specific HMTs such as G9a. It also has some inhibitory effects on SET7, EZH2, and SET7/9. Chaetocin can also induce cellular oxidative stress, selectively killing cancer cells and rapidly-proliferating primary cells. It is a fungal myotoxin. The inhibitor is useful in epigenetics and cancer research.

UNC0638 is a selective inhibitor of G9a and G9a-like protein (GLP), also known as EHMT1, with IC50's in the very low (<20) nM range. It also exhibits very weak activity against JMJD2E (IC50 ~4.5 µM), but the selectivity for G9a and GLP is over 200-fold. UNC0638 was inactive against SUV39H1, SUV39H2, EZH2), SETD7, MLL, SMYD3, DOT1L, SETD8, PRDM1, PRMT1 and PRMT3. UNC0638 exhibits only extremely weak inhibition of DNMT1 (IC50 >100 µM).