Mycotoxins

Monomethyl Auristatin E (MMAE) is a synthetic analog of dolastatin 10 that similarly inhibits tubulin polymerization and exhibits potent cytotoxicity. It is commonly conjugated with monoclonal antibodies directed at antigens specific to cancer cells for tumor-directed cytotoxicity.

DM1 with a reactive linker SMCC, which can react with antibody to make antibody drug conjugate, as a potent EGFR inhibitor and it overcomes resistant to EGFR.

Aflatrem is the secondary metabolite of Aspergillus flavus. It is able to induce degeneration of neuronal processes in hippocampal neurotransmitter systems at low dose. It potentiates the gamma-aminobutyric acid (GABA)-induced chloride current. It is a tremorgenic mycotoxin with acute neurotoxic effect.

Deoxynivalenol is a type B trichothecene, an epoxy-sesquiterpenoid. This mycotoxin can induce vomiting, diarrhea, and weight loss as well as other physiological and toxicological effects. It inhibits protein biosynthesis, binds to peptidyl transferase, and inhibits the synthesis of RNA and DNA, contributing to immunotoxicity.

Spliceostatin A is a potent inhibitor of in vitro and in vivo pre-mRNA splicing. It was shown to inhibit splicing and to interact with an essential component of the spliceosome, SF3b. Spliceostatin A is an inhibitor of RNA synthesis with excellent anticancer activity against a variety of human cancer cell lines. Spliceostatin A inhibits mitotic clone expansion and adipogenesis.

Irofulven is a semisynthetic sesquiterpene derivative of illudin S, a natural toxin isolated from the fungus Omphalotus illudens. Irofulven alkylates DNA and protein macromolecules, forms adducts, and arrests cells in the S-phase of the cell cycle.

gamma-Mangostin isolated from the fruit of Garcinia cambogia is an HIV protease inhibitor. gamma-Mangostin is cytotoxic to HL-60, SMMC-7721, A549, MCF-7, and SW480 cancer cells and BEAS-2B non-cancerous pulmonary epithelial cells in vitro (IC50s = 7.39, 6.57, 10.07, 5.33, 8.4, and 7.43 μM, respectively).

DM4 is an anti-tubulin agent that inhibits cell division. DM4 can be used to prepare antibody-drug conjugates. DM4 binds to tubulin at the maytansine-binding site, disrupting microtubule assembly/disassembly dynamics and inhibiting mitosis.

Mertansine, the cytotoxic component in antibody-drug conjugates, is attached to a monoclonal antibody through reaction of the thiol group with the SPP (N-succinimidyl 4-(2-pyridyldithio)) linker or SMCC (4-(3-mercapto-2,5-dioxo-1 pyrrolidinylmethyl)-cylohexanecarboxylic acid) linkerto create an antibody-drug conjugate. It derives from a maytansine.

Maytansinol is an ansamacrolide isolated from P. verrucose. It was shown to inhibit microtubule assembly and induces microtubule disassembly in vitro. It exhibits antitumor activity.

It is produced by the strain of Nocardia sp. C-15003(N-1). It has the function of anti-tumor, anti-plant pathogenic fungi, skin fungi and protozoa, and has no antibacterial activity.

Calicheamicins are a class of enediyne antitumor antibiotics derived from the bacterium Micromonospora echinospora, The main component is calicheamicin γ1. It has strong anti-Gram-positive bacteria activity and anti-tumor effect.

It is a potent cell cycle inhibitor isolated from Pseudomonas sp. No.2663. It exhibits potent antitumor activities against tumor cell lines via binding to the spliceosome and modulating pre-mRNA splicing.

Daunorubicin HCl inhibits both DNA and RNA synthesis and inhibits DNA synthesis with Ki of 0.02 μM.

Exatecan mesylate is a semisynthetic, water-soluble derivative of camptothecin with antineoplastic activity. Exatecan mesylate inhibits topoisomerase I activity by stabilizing the cleavable complex between topoisomerase I and DNA and inhibiting the religation of DNA breaks, thereby inhibiting DNA replication and triggering apoptotic cell death. This agent does not require enzymatic activation and exhibits greater potency than camptothecin and other camptothecin analogs.