Bioactive Small Molecules for Epigenetics Research

Epigenetic modification of chromatin includes methylation of genomic DNA as well as post-translational modification of chromatin-associated proteins, mainly histones. Cell-permeable small-molecule modulators have become a valuable tool in the investigation of gene and protein functions. The use of small molecules to modulate cellular and in vivo systems is receiving strong interest among researchers in academia as well as pharma. The discovery of small molecule regulators (activators or inhibitors) of epigenetic modification enzymes provides researchers with pharmacological tools with which to investigate the biological consequences of chromatin modifications. The major classes of inhibitors/modulators are classified based on their activity and use.

DNA Methyltransferase Inhibitors
Histone Methylation Modulators
Histone Deacetylase Inhibitors
Histone Acetyltransferase Inhibitors

DNA Methyltransferase Inhibitors

DNA methyltransferases are a family of enzymes that catalyze the transfer of methyl group to DNA. There are five related DNA cytosine- 5-methyltransferases (DNMTs) that transfer a methyl group from S-adenosylmethionine (AdoMet, SAM) to the C-5 position of cytosine. Inhibitors have been shown to have anti-proliferative activity. They can reactivate the expression of genes that have been repressed by DNA methylation.

Nucleoside analog inhibitors:
Require DNA incorporation for DNMT inhibition.

Description Product No.
5-Azacytidine ≥98% (HPLC) A2385-100MG
5-Azacytidine ≥98% (HPLC) A2385-250MG
5-Azacytidine ≥98% (HPLC) A2385-1G
Zebularine ≥98% (HPLC), solid Z4775-5MG
Zebularine ≥98% (HPLC), solid Z4775-25MG

Non-nucleoside analog inhibitors:
Block DNMT directly without DNA incorporation.

Description Product No.
Caffeic acid purum, ≥95.0% (HPLC) 60020-10G-F
Caffeic acid purum, ≥95.0% (HPLC) 60020-50G-F
Chlorogenic acid C3878-250MG
Chlorogenic acid C3878-1G
Chlorogenic acid C3878-5G
(-)-Epigallocatechin gallate ≥95%, from green tea E4143-50MG
Hydralazine H1753-5G
Hydralazine H1753-10G
Hydralazine H1753-50G
Procainamide hydrochloride P9391-25G
Procainamide hydrochloride P9391-100G
Procaine hydrochloride ≥97% P9879-50G
Procaine hydrochloride ≥97% P9879-100G
Procaine hydrochloride ≥97% P9879-250G
Psammaplin A ≥97% (HPLC), solid P8749-5MG
RG108 ≥98% (HPLC), solid R8279-10MG

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Histone Methylation

Histone methyltransferases (HMTs), histone-lysine N-methyltransferase and histone-arginine N-methyltransferase, are enzymes which catalyzye the transfer of one to three methyl groups from the cofactor S-Adenosyl methionine to lysine and arginine residues of histone proteins.

Histone Lysine Methyltransferase (HKMT) inhibitors

Description Product No.
BIX 01294 trihydrochloride hydrate ≥98% (HPLC), white solid B9311-5MG
BIX 01294 trihydrochloride hydrate ≥98% (HPLC), white solid B9311-25MG
Chaetocin from Chaetomium minutum >95% (HPLC), >98% (TLC) C9492-1MG

Histone Lysine Demethylase inhibitors:
Lysine specific demethylase I (LSDI, KIA0601, BHC10) has close homology to monoamine oxidases (MAOs), and hence the classic MAO inhibitors pargyline and tranylcypromine have been found to inhibit LSD1, although not with high potency (>100µM).

Description Product No.
Pargyline hydrochloride P8013-500MG
Pargyline hydrochloride P8013-1G
Pargyline hydrochloride P8013-5G
trans-2-Phenylcyclopropylamine hydrochloride P8511-250MG
trans-2-Phenylcyclopropylamine hydrochloride P8511-1G
trans-2-Phenylcyclopropylamine hydrochloride P8511-5G

Protein Arginine Methyltransferase (PRMT) modulators:
Most of the PRMT inhibitors mentioned in literature are nonselective and may also inhibit DNMTs and HKMTs.

Description Product No.
AMI-1 sodium salt hydrate ≥98% (HPLC) A9232-5MG
AMI-1 sodium salt hydrate ≥98% (HPLC) A9232-25MG
AMI-5 (eosin Y) 119830-25G
AMI-5 (eosin Y) 119830-100G
5'-Deoxy-5'-(methylthio)adenosine D5011-25MG
5'-Deoxy-5'-(methylthio)adenosine D5011-100MG
5'-Deoxy-5'-(methylthio)adenosine D5011-250MG
S-(5'-Adenosyl)-L-homocysteine crystalline A9384-10MG
S-(5'-Adenosyl)-L-homocysteine crystalline A9384-25MG
S-(5'-Adenosyl)-L-homocysteine crystalline A9384-50MG
S-(5'-Adenosyl)-L-homocysteine crystalline A9384-100MG

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Histone Deacetylases

Histone deacetylases (HDACs) are enzymes that remove acetyl groups from lysines of histones and a number of other regulatory and structural proteins. They play critical roles in chromatin remodeling and are involved in transcription regulation, cell-cycle progression, cell survival and differentiation. So far, 18 HDACs have been identified and divided into 3 distinct enzyme classes.

Class I and II HDACs are zinc dependent. Class I, homologous to yeast Rpd3, includes HDAC1, 2, 3, and 8. Class II (HDAC4, 5, 6, 7, 9, 10) resembles yeast Hda1. Class I and II HDACs are associated with malignant transformations and are targets for cancer drugs. Inhibitors of Class I and II HDACs are largely classified into four groups on the basis of their chemical structures.

Short-chain fatty acid inhibitors

Description Product No.
Sodium butyrate B5887-250MG
Sodium butyrate B5887-1G
Sodium butyrate B5887-5G
Valproic acid P4543-10G
Valproic acid P4543-25G
Valproic acid P4543-100G

Hydroxamic acid inhibitors:
The most widely used HDAC inhibitors are hydroxamic acid- based. They are nonspecific for HDAC subclass.

Description Product No.
MC1568 M1824-5MG
MC1568 M1824-25MG
Oxamflatin ≥98% (HPLC), solid O3139-1MG
Oxamflatin ≥98% (HPLC), solid O1319-5MG
Scriptaid ≥95% (H-NMR), solid S7817-1MG
Scriptaid ≥95% (H-NMR), solid S7817-5MG
Trichostatin A 5 mM in DMSO (0.2 µm-filtered), from Streptomyces sp. T1952-200ul
Trichostatin A ≥98% (HPLC), from Streptomyces sp. T8552-1mg
Trichostatin A ≥98% (HPLC), from Streptomyces sp. T8552-5mg

Benzamide inhibitors

Description Product No.
CI-994 ≥98% (HPLC), powder C0621-5MG
CI-994 ≥98% (HPLC), powder C0621-25MG

Cyclic tetrapeptide and natural product inhibitors:
Most show selectivity for Class I HDACs.

Description Product No.
Apicidin ≥98% (HPLC), from microbial, solid A8851-1MG
Apicidin ≥98% (HPLC), from microbial, solid A8851-5MG
(-)-Depudecin >95% (HPLC), from microbial D5816-1MG
Trapoxin A T2580-1MG
Trapoxin A T2580-5MG

Other HDAC inhibitors:
No data suggesting HDAC class selectivity.

Description Product No.
APHA Compound 8 ≥98% (HPLC), solid A2478-1MG
BATCP ≥98% (HPLC), solid B4061-2MG
Cambinol C0497-200ul
MOCPAC ≥95% (HPLC), solid M2195-2MG
M344 M5820-1MG
PTACH ≥98% (HPLC), solid P5874-2MG
Resveratrol >99% (GC) R5010-100MG
Resveratrol >99% (GC) R5010-500MG
Splitomicin ≥98% (HPLC), solid S4068-5MG

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Histone Acetyltransferases (HAT)

Histone acetyltransferases (HAT) are enzymes that acetylate conserved lysine amino acids on histone proteins by transferring an acetyl group from acetyl CoA to form ε-N-acetyl lysine. Histone acetylation is generally linked to transcriptional activation. These are generally associated with euchromatin.

HAT inhibitors:
Histone acetyltransferases (HATs) act as transcriptional coactivators. Histone acetylation plays an important role in regulating the chromatin structure and is tightly regulated by two classes of enzyme, histone acetyltransferases (HAT) and histone deacetylases (HDAC). Deregulated HAT and HDAC activity plays a role in the development of a range of cancers. Consequently, inhibitors of these enzymes have potential as anticancer agents.

Description Product No.
Anacardic acid A7236-5MG
Anacardic acid A7236-25MG
CPTH2 ≥98% (HPLC), powder C9873-5MG
CPTH2 ≥98% (HPLC), powder C9873-25MG
Curcumin from Curcuma longa (Turmeric), powder C1386-5G
Curcumin from Curcuma longa (Turmeric), powder C1386-10G
Curcumin from Curcuma longa (Turmeric), powder C1386-50G
Garcinol ≥95% G5173-5MG
Garcinol ≥95% G5173-25MG
MB-3 M2449-5MG

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