Chemicals & Small Molecules

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).

(R)-MG132 is a potent, cell permeable and reversible inhibitor of proteasomes. It can inhibit proteasome activity in lysates of J558L multiple myeloma cells and EMT6 breast cancer cells. In comparison to (S)-MG132, the (R)-MG132 stereoisomer is a more effective inhibitor of chymotrypsin-like (ChTL), trypsin-like (TL), and peptidylglutamyl peptide hydrolyzing proteasome (PGPH) activities.

IU1 is a small molecule, reversible inhibitor of deubiquitination by USP14. It selectively stimulates ubiquitin-dependent protein degradation in vitro at 34 µM and in MEF cells at 50 µM. IU1 can also reduce accumulation of oxidized proteins in HEK293 cells, which alleviates cytotoxicity induced by oxidative stress.

AGK2 is a selective, cell-permeable inhibitor of SIRT2. It has minimal effects SIRT1 and SIRT3 at 10-fold higher levels compared to SIRT2. Useful for studing SIRT2 in neurodegeneration and aging, as well as cell cycle progression and tumorigenesis.

BAY-11-7082 is a selective and irreversible inhibitor of NF-κB activation by blocking TNF-α-induced phosphorylation of IκB-α without affecting constitutive IκB-α phosphorylation. It also inhibits the TNF-α-induced surface expression of adhesion molecules ICAM-1, VCAM-1, and E-selectin in human endothelial cells.

(S)-MG132, also known as Z-Leu-Leu-Leu-CHO, is a potent, reversible and cell-permeable inhibitor of proteasomes that inhibits cell growth in B16 and IPC227F cells. It also inhibits NF-κB activation, sensitizing a variety of carcinoma cell lines to apoptosis.