maytansine has been researched along with rhizoxin* in 11 studies
3 review(s) available for maytansine and rhizoxin
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Tubulin as a target for anticancer drugs: agents which interact with the mitotic spindle.
Tubulin is the biochemical target for several clinically used anticancer drugs, including paclitaxel and the vinca alkaloids vincristine and vinblastine. This review describes both the natural and synthetic agents which are known to interact with tubulin. Syntheses of the more complex agents are referenced and the potential clinical use of the compounds is discussed. This review describes the biochemistry of tubulin, microtubules, and the mitotic spindle. The agents are discussed in relation to the type of binding site on the protein with which they interact. These are the colchicine, vinca alkaloid, rhizoxin/maytansine, and tubulin sulfhydryl binding sites. Also included are the agents which either bind at other sites or unknown sites on tubulin. The literature is reviewed up to October 1997. Topics: Antibiotics, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Binding Sites; Colchicine; Drug Design; Humans; Lactones; Macrolides; Maytansine; Microtubules; Paclitaxel; Protein Binding; Spindle Apparatus; Sulfhydryl Reagents; Tubulin; Tubulin Modulators; Vinblastine; Vincristine | 1998 |
[Inhibitors of tubulin assembly: specially on rhizoxin-maytansine site ligands].
Topics: Animals; Binding Sites; Colchicine; Lactones; Ligands; Macrolides; Maytansine; Tubulin; Tubulin Modulators; Vinblastine | 1993 |
Natural products which interact with tubulin in the vinca domain: maytansine, rhizoxin, phomopsin A, dolastatins 10 and 15 and halichondrin B.
This paper summarizes published data on the interactions of tubulin with antimitotic compounds that inhibit the binding of vinca alkaloids to the protein. These are all relatively complex natural products isolated from higher plants, fungi and marine invertebrate animals. These agents are maytansine, rhizoxin, phomopsin A, dolastatins 10 and 15 and halichondrin B and their congeners. Effects on tubulin polymerization, ligand binding interactions and structure-activity relationships are emphasized. Topics: Animals; Antibiotics, Antineoplastic; Antineoplastic Agents; Depsipeptides; Ethers, Cyclic; Lactones; Macrolides; Maytansine; Mycotoxins; Oligopeptides; Tubulin; Vinca Alkaloids | 1992 |
8 other study(ies) available for maytansine and rhizoxin
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A new tubulin-binding site and pharmacophore for microtubule-destabilizing anticancer drugs.
The recent success of antibody-drug conjugates (ADCs) in the treatment of cancer has led to a revived interest in microtubule-destabilizing agents. Here, we determined the high-resolution crystal structure of the complex between tubulin and maytansine, which is part of an ADC that is approved by the US Food and Drug Administration (FDA) for the treatment of advanced breast cancer. We found that the drug binds to a site on β-tubulin that is distinct from the vinca domain and that blocks the formation of longitudinal tubulin interactions in microtubules. We also solved crystal structures of tubulin in complex with both a variant of rhizoxin and the phase 1 drug PM060184. Consistent with biochemical and mutagenesis data, we found that the two compounds bound to the same site as maytansine and that the structures revealed a common pharmacophore for the three ligands. Our results delineate a distinct molecular mechanism of action for the inhibition of microtubule assembly by clinically relevant agents. They further provide a structural basis for the rational design of potent microtubule-destabilizing agents, thus opening opportunities for the development of next-generation ADCs for the treatment of cancer. Topics: Animals; Antibiotics, Antineoplastic; Antineoplastic Agents, Phytogenic; Binding Sites; Breast Neoplasms; Cattle; Clinical Trials, Phase I as Topic; Crystallography, X-Ray; Female; Humans; Macrolides; Maytansine; Microtubules; Polyketides; Pyrones; Tubulin; Tubulin Modulators | 2014 |
A previously undescribed tubulin binder.
Topics: Animals; Antibiotics, Antineoplastic; Antineoplastic Agents, Phytogenic; Female; Humans; Macrolides; Maytansine; Microtubules; Polyketides; Pyrones; Tubulin; Tubulin Modulators | 2014 |
Regulatory volume decrease in Leishmania mexicana: effect of anti-microtubule drugs.
The trypanosomatid cytoskeleton is responsible for the parasite's shape and it is modulated throughout the different stages of the parasite's life cycle. When parasites are exposed to media with reduced osmolarity, they initially swell, but subsequently undergo compensatory shrinking referred to as regulatory volume decrease (RVD). We studied the effects of anti-microtubule (Mt) drugs on the proliferation of Leishmania mexicana promastigotes and their capacity to undergo RVD. All of the drugs tested exerted antiproliferative effects of varying magnitudes [ansamitocin P3 (AP3)> trifluoperazine > taxol > rhizoxin > chlorpromazine]. No direct relationship was found between antiproliferative drug treatment and RVD. Similarly, Mt stability was not affected by drug treatment. Ansamitocin P3, which is effective at nanomolar concentrations, blocked amastigote-promastigote differentiation and was the only drug that impeded RVD, as measured by light dispersion. AP3 induced 2 kinetoplasts (Kt) 1 nucleus cells that had numerous flagella-associated Kts throughout the cell. These results suggest that the dramatic morphological changes induced by AP3 alter the spatial organisation and directionality of the Mts that are necessary for the parasite's hypotonic stress-induced shape change, as well as its recovery. Topics: Animals; Chlorpromazine; Cytoskeleton; Leishmania mexicana; Macrolides; Maytansine; Mice; Paclitaxel; Trifluoperazine; Tubulin Modulators | 2013 |
Binding selectivity of rhizoxin, phomopsin A, vinblastine, and ansamitocin P-3 to fungal tubulins: differential interactions of these antimitotic agents with brain and fungal tubulins.
The binding of four potent antimitotic agents, rhizoxin (RZX), phomopsin A (PMS-A), ansamitocin P-3 (ASMP-3), and vinblastine (VLB), to tubulins from RZX-sensitive and -resistant strains of Aspergillus nidulans, Schizosaccharomyces pombe, and Saccharomyces cerevisiae was investigated. Mycelial extracts to which RZX could bind contained beta-tubulin with Asn as the 100th amino acid residue (Asn-100) in all cases, and those without affinity for RZX contained beta-tubulins with either Ile-100 or Val-100. Though PMS-A shares the same binding site as RZX and ASMP-3 on porcine brain tubulin (Asn-100), only ASMP-3 bound Asn-100 fungal tubulins in a competitive manner with respect to RZX. PMS-A and VLB, which strongly bind to porcine brain tubulin, did not bind to any of the fungal mycelial extracts examined. The results indicate differential interactions of these antimitotic agents with brain and fungal tubulins. Topics: Animals; Antineoplastic Agents; Aspergillus nidulans; Binding Sites; Binding, Competitive; Brain; Brain Chemistry; Fungi; Lactones; Macrolides; Maytansine; Mycotoxins; Saccharomyces cerevisiae; Schizosaccharomyces; Swine; Tubulin; Vinblastine | 1992 |
Interaction of phomopsin A with porcine brain tubulin. Inhibition of tubulin polymerization and binding at a rhizoxin binding site.
Phomopsin A is an antimitotic cyclic peptide containing a 13-member ring including an ether linkage. It was isolated from the fungus Phomopsis leptostromiformis as the causal agent of lupinosis. Phomopsin A strongly inhibited microtubule assembly (IC50: 2.4 microM). Our study using radiolabeled phomopsin A, prepared biosynthetically by feeding L-[U-14C]isoleucine to the culture of P. leptostromiformis, indicated that at least two binding sites of phomopsin A exist on tubulin on the basis of a Scatchard analysis; i.e. the dissociation constants of a high affinity site (Kd1) and a low affinity site (Kd2) at 37 degrees were determined to be 1 x 10(-8) and 3 x 10(-7) M, respectively. Phomopsin A inhibited the binding of radiolabeled rhizoxin to tubulin with an inhibition constant (Ki) of 0.8 x 10(-8) M. This showed that the high affinity site of phomopsin A is identical to the rhizoxin binding site. The binding of the radiolabeled phomopsin A was also inhibited by rhizoxin and ansamitocin P-3, with an inhibition constant of 10(-7) M, and to a lesser extent by vinblastine. Phomopsin A had no inhibitory effect on colchicine binding to tubulin. Topics: Animals; Binding Sites; Binding, Competitive; Brain; Colchicine; Kinetics; Lactones; Macrolides; Maytansine; Microtubule Proteins; Mycotoxins; Polymers; Protein Conformation; Structure-Activity Relationship; Swine; Tubulin; Tubulin Modulators; Vinblastine | 1992 |
Interaction of rhizoxin with bovine brain tubulin.
Rhizoxin is an antitumor drug prepared from the fungus Rhizopus chinensis. It is an inhibitor of microtubule assembly and a potent competitive inhibitor of the binding of tubulin of ansamitocin P-3, a maytansine analogue. Rhizoxin also weakly inhibits vinblastine binding to tubulin. We have previously found that maytansine and vinblastine differ strikingly from each other in many ways, including their effects on tubulin sulfhydryl groups and on tubulin decay. Since the structure of rhizoxin is very different from that of vinblastine and only slightly resembles that of maytansine, we decided to compare its interaction with tubulin with those of the other two drugs, using systems which discriminate between the effects of the latter two drugs. We found that rhizoxin acts like maytansine in that it completely prevents formation of an intrachain cross-link in beta-tubulin by N,N'-ethylenebis(iodoacetamide), whereas vinblastine only partially inhibits this. Half-maximal inhibition of formation of this cross-link was observed at 2.5 microM rhizoxin. We found previously that the rate of binding of tubulin to the fluorescent probe bis(8-anilinonaphthalene 1-sulfonate) is a good indicator of tubulin decay and that vinblastine strongly inhibits this, whereas maytansine has no effect. We here report that rhizoxin acts like maytansine in that it has no effect on decay. Thus, despite the fact that its resemblance to maytansine is small, rhizoxin appears to interact with tubulin in very much the same way as does maytansine. Topics: Animals; Antibiotics, Antineoplastic; Brain; Cattle; Colchicine; Cross-Linking Reagents; Ethylenediamines; Kinetics; Lactones; Macrolides; Maytansine; Molecular Structure; Mycotoxins; Podophyllotoxin; Tubulin; Vinblastine | 1990 |
Rhizoxin binding to tubulin at the maytansine-binding site.
The binding of rhizoxin, a potent inhibitor of mitosis and in vitro microtubule assembly, to porcine brain tubulin was studied. Tubulin possesses one binding site for rhizoxin per molecule with a dissociation constant (Kd) of 1.7.10(-7) M. Ansamitocin P-3, a homologue of maytansine, was a competitive inhibitor of rhizoxin binding, with an inhibition constant of 1.3.10(-7) M. Vinblastine also inhibited rhizoxin binding, but was not fully competitive, and the inhibition constant was 2.9.10(-6) M. In contrast, both rhizoxin and ansamitocin P-3 were potent inhibitors of vinblastine binding. Rhizoxin inhibited tau-promoted tubulin assembly, but it, differing from vinblastine, did not induce tubulin aggregation into spirals, even at a concentration as high as 2.10(-5) M. In addition, rhizoxin strongly inhibited vinblastine-induced tau-dependent tubulin aggregation. Rhizoxin binding to tubulin was completely independent from colchicine binding. These effects resemble those of maytansine. The results suggested that rhizoxin binds to the maytansine-binding site and that the binding sites of rhizoxin and vinblastine are not the same. Topics: Animals; Binding Sites; Binding, Competitive; Colchicine; Kinetics; Lactones; Macrolides; Maytansine; Microscopy, Electron; Microtubule-Associated Proteins; Microtubules; Oxazines; Swine; tau Proteins; Tubulin; Vinblastine | 1987 |
Rhizoxin, a macrocyclic lactone antibiotic, as a new antitumor agent against human and murine tumor cells and their vincristine-resistant sublines.
Rhizoxin, isolated from a plant pathogenic fungus which causes rice seedling blight, inhibits the mitosis of the tumor cells in a manner similar to that of Vinca alkaloids as revealed by morphological study and flow cytometry analysis. This new 16-membered macrocyclic lactone showed similar chemotherapeutic effects to those of vincristine against L1210 and P388 leukemia-bearing mice. The drug is also effective against B16 melanoma inoculated i.p. or s.c. Rhizoxin, in contrast to the ansamacrolide, maytansine, was effective against human and murine tumor cells resistant to vincristine and Adriamycin in vitro and in vivo. A maximum 60% increase in life span was obtained in mice inoculated with P388 leukemia resistant to vincristine. Rhizoxin showed greater cytotoxicity in cultured tumor cells than did vincristine. Rhizoxin seems to bear consideration for further development as a new chemotherapeutic agent. Topics: Animals; Antibiotics, Antineoplastic; Cell Cycle; Cells, Cultured; Drug Resistance; Female; Lactones; Leukemia L1210; Leukemia P388; Leukemia, Experimental; Macrolides; Maytansine; Melanoma; Mice; Microscopy, Electron, Scanning | 1986 |