Table 2.

Natural products that act as interfacial inhibitors

DrugOriginSubstrateMechanismReferences
CamptothecinChinese treeTopoisomerase I-DNA complexStabilizes a kinetic intermediate of the DNA cleavage enzymic reaction(15, 25, 47)
Brefeldin AAscomycetesArf-GDP-GEF complexStabilizes a kinetic protein-protein intermediate undergoing conformational changes(48, 49)
CyclosporineSoil fungusCyclophilin/calcineurinHinders access to the active site of the protein phosphatase calcineurin by artificially creating a protein-protein interface(50, 51)
FK506/tacrolimusActinomycetes (fungi-like bacteria)FKBP/calcineurinIdem(52, 53)
ForskolinIndian herbHeterodimer of adenylyl cyclaseActivates the enzyme by stabilizing the heterodimer catalytic site in an active conformation(54)
FusicoccinFungus (plant parasite)14-3-3/ATPase complexOverstabilizes a regulatory complex(55)
RapamycinSoil bacteriaFKBP/FRAPPromotes dimerization of FKBP12 with FRAP and inhibits mammalian target of rapamycin(56)
ColchicineCrocusTubulin heterodimerPrevents tubulin polymerization by stabilizing a curved tubulin heterodimer(57)
VinblastineVincaTubulin heterodimerPrevents tubulin polymerization by stabilizing a curved tubulin heterodimer(58)
TaxolTree (Taxus baccatus)β-TubulinStabilizes microtubules(59)
Epothilone AMyxobacteriaβ-TubulinStabilizes microtubules(60)
KirromycinFungusAntibiotics: bacterial ribosomesStabilization of translation elongation factors EF-Tu(61, 62)
Fusidic acidFungusBacterial ribosomeStabilization of translation factor EF-G(61, 62)
ThiostreptonStreptomycesBacterial ribosomePrevents EF-G binding by altering the interface between ribosomal protein L11 and rRNA(63)
Dexrazoxane (=ICRF-187)SyntheticTopoisomerase II-ATP complexStabilizes the closed topoisomerase II dimer(64, 65)
α-Amanitin“Black cap” mushroomRNA polymerase IIBinds to Rpb1-Rpb2 interface and prevents polymerase II translocation(66)