Enzyme inhibitors

Triacsin C, originally isolated from Streptomyces sp., is a polyunsaturated fatty acid derivative. It has been found to be an acyl-CoA synthetase inhibitor as well as an effective vasodilator. It selectively inhibits arachidonoyl-CoA synthetase in intact cells and the nonspecific acyl-CoA synthetase in cell sonicates, as well as inhibits neutrophil functions.

Hypocrellin A is a natural perylene quinine photosensitizer isolated from Hypocrella bambusae. It is a potent PKC inhibitor.

Chrysomycin A is a C-glycoside antitumor antibiotic isolated from Streptomyces, and it is an inhibitor of the catalytic activity of human topoisomerase II. It has effective antibacterial, antifungal, antiviral and antitumor activities. It may act as a light-activated cross-linking agent between DNA and histones.

Bryostatin 1, a structurally unique macrolactone marine natural product, is a protein kinase C (PKC) activator that binds with high affinity (Ki = 1.35 nM). Bryostatin 1 fails to mimic many effects caused by PMA and actually blocks some PMA-induced response in a variety of cells and tissues. Animal tests have shown bryostatin 1 may alleviate brain damage after a stroke.

Chrysomycin B is a minor analogue in a complex of C-glycoside antitumor active substances isolated from Streptomyces. Its activity is lower than that of its vinyl analogue (Chrysomycin A), but it still has strong anti-tumor activity and is an inhibitor of the catalytic activity of human topoisomerase II. It can be used as a light-activated cross-linking agent for DNA and histones.

Bryostatin 2, an analog of Bryostatin 1, is an activator of PKC (protein kinase C) with anti-tumor properties. Bryostatin 2 inhibits DNA synthesis at 100 nM in SH-SY5Y human neuroblastoma cells.

Sclerotiorin is a metabolite isolated from Penicillium species. It inhibits soybean lipoxygenase-1 (LOX-1) with IC50 value of 4.2 µM. It also exhibits antioxidant property by scavenging free radical with an ED50 of 0.12 μM.

Bacitracin F is a major Bacitracin analog, a peptide antibiotic used as an inhibitor of protein disulfide isomerase (PDI). It is isolated from Bacillus.

Teleocidin A1 is a powerful nematicide and acaricide produced by Streptomyces, which acts as an effective activator of protein kinase C, a tumor promoter, an inducer of colony stimulating factors, and regulator of expression of several genes.

Obscurolide A1 is a weak phosphodiesterase inhibitor isolated from Streptomyces viridochromogenes.

Oligomycin, a mixture of A, B, and C Oligomycin isomers, has been found to be a macrolide compound and could exhibit effect in restraining mitochondrial ATP-synthase. It is isolated from Streptomyces diastatochromogenes.

Bevacizumab is an angiogenesis inhibiting monoclonal antibody which is commonly used to treat certain metastatic cancers. It acts via inhibiting vascular endothelial growth factor A (VEGF-A).

A semi-synthetic tetracycline formed by a mannich condensation of formaldehyde and 4-hydroxyethylpiperazine with tetracyclin. It inhibits the formation of penicillinase, the enzyme that inactivates penicillin in bacteria. It is used in salt form with penicillin V for parenteral use.

Oligomycin D is a macrolide compound produced by Streptomyces, which can inhibit mitochondrial F1FO-ATPase.

Clasto-Lactacystin β-lactone is a microbial metabolite isolated from Streptomyces that is now widely used as a selective inhibitor of the 20S proteasome. Clasto-lactacystin β-lactone was later identified as the active metabolite of lactacystin, resulting from the elimination of cysteine and the formation of a reactive β-lactone. It is 20-fold more potent than Lactacystin.

L-Methionine-(S,R)-sulfoximine is an inhibitor of glutamine synthetase and a sulfoximine derivative of L-methionine.

Reveromycin C is a polyketide isolated from Streptomyces. It is an antibiotic inhibitor with mitotic activity that responds to EGF.

KT 5720, an anti-bacterial agent synthesized by the fungus Nocardiopsis sp, specifically blocks PKA signaling through competitive inhibition of ATP with a Ki value of 60 nM.

KT 5823 is a cell-permeable, selective inhibitor of cGMP-dependent protein kinase (PKG) (Ki values are 0.23, 4 and > 10 μM for inhibition of PKG, PKC and PKA respectively). KT 5823 is often used in intact cells to assess the role of PKG in signaling, although there are cases where it poorly inhibits PKG in cells.

Reveromycin D is a bacterial metabolite isolated from Streptomyces. It inhibits EGF-induced mitotic activity in Balb/MK cells and has pH-dependent antifungal activity against Candida albicans.