32 results about "Tubulin binding" patented technology

Novel stilbenoid compounds and their prodrug forms are disclosed, which serve as potent vascular targeting agents useful for the treatment of solid tumor cancers and other diseases associated with unwanted neovascularization. The novel stilbenoid compounds are tubulin-binding stilbenoid analogs structurally related to combretastatin A-1 and combretastatin A-4. The prodrug forms serve as potent vascular targeting agents (VTAs) useful for the treatment of solid tumor cancers and diseases associated with retinal neovascularization.

Analogs of combretastatin have been discovered which demonstrate impressive cytotoxicity as well as a remarkable ability to inhibit tubulin polymerization. Such compounds are excellent clinical candidates for the treatment of cancer in humans. In addition, certain of these ligands, as pro-drugs, may well prove to be tumor selective vascular targeting chemotherapeutic agents or to have vascular targeting activity resulting in the selective prevention and / or destruction of nonmalignant proliferating vasculature.

This disclosure relates to antimitotic compounds, compositions comprising therapeutically effective amounts of these compounds, and methods of using those compounds and compositions in treating hyperproliferative disorders, e.g., cancers and myelodysplastic syndromes.

Compounds, pharmaceutical compositions including the compounds, and methods of preparation and use thereof are disclosed. The compounds are noscapine analogs. The compounds and compositions can be used to treat and / or prevent a wide variety of cancers, including drug resistant cancers. While the antitussive plant alkaloid, noscapine, binds tubulin, displays anticancer activity, and has a safe pharmacological profile in humans, structure-function analyses pointed to a proton at position 9 of the isoquinoline ring that can be modified without compromising tubulin binding activity. Noscapine analogs with various functional moieties at position 9 on the isoquinoline ring kill human cancer cells resistant to other anti-microtubule agents, such as vincas and taxanes.

The invention discloses a linderane compound capable of inhibiting microtubulin and a preparation method and application of the linderane compound capable of inhibiting the microtubulin. The linderane compound is shown as the formula (I), wherein each of R1 and R3 refers to alkane group, alkylene or alkyne group, and each of R2 and R4 refers to H, hydroxyl, alkoxy, amino or halogeno. The linderane compound is capable of competing with radiolabeled colchicine in a binding site to inhibit binding of the colchicine and the microtubulin and acts in a dose-dependent manner. Both the linderane compound and the colchicine can inhibit microtubulin polymerization, and the linderane compound is powerful in antimicrotubular polymerization. The linderane compound is simple in preparation method and easy to operate and can be used for preparing various tumor treatment medicines.

The invention discloses a tubulin-based nitrine-beta-lactam micromolecule probe and a preparation method and application and belongs to the field of medicinal chemistry. A beta-lactam mother nucleus is combined with nitrine active unit, so that simplicity and high efficiency are realized. The probe has a structural general formula as follows. Molecular in-vitro anti-cancer activity experiments of the probe show that the probe has certain inhibition effect on various tumor cells MCF-7, MGC-803 and A549. Especailly, activity of nitrine-beta-lactam probe molecule I-9 to MGC-803 cells is 85nM. On the other side, the compound can be combined with tubulin to inhibit tubulin polymerization and can serve as a potential tubulin micromolecule probe. By the probe, the problem that nitrine-type tubulin probes are few in type, troublesome to synthesize and high in cost is solved, and development of drug for inhibiting tubulin polymerization is facilitated.

The present invention relates to (E)-ethyl 2-(2-methyl-3-((2-(naphtho[2,1-b]furan-2-carbonyl)hydrazono)methyl)-1H-indol-1-yl)acetate as a novel tubulin polymerization inhibitor and a method for synthesizing the same. The compound of the present invention can inhibit mitosis and induce apoptosis and thus be used as an anticancer agent, by binding to tubulin to inhibit microtube polymerization. According to the synthesis method of the present invention, the reaction is simplified and the efficiency is 60% or higher, leading to a very high yield, thereby providing an effective synthesis method.

The invention discloses application of a compound epothilone B to preparing a medicine for healing cornea neurotrauma, and belongs to the field of biological medicines. The pharmacodynamic experiment proves that a rat suffering from cornea neurotrauma is taken as an experimental subject and the area of a cornea nerve is obviously increased by EpoB and is close to the normal level. The compound EpoB stabilizes the tubulin binding, so that the tubulin polymerization is promoted, the depolymerization of a microtube is inhibited, the concentration of the tubulin is increased, the repairing and the reconstruction of the neurotrauma are promoted, and the normal structure and functions of the cornea are maintained. The EpoB has better treatment effects on the function injuries and the cornea nerve lesion caused by refractive surgery, keratoplasty, herpes simplex keratitis, xerophthalmia, diabetes and long-term use of eyedrops, and alleviates the eye symptoms of a patient; and the medicine is low in toxicity and high in stability, and has an important development and application prospect.

The invention belongs to the biomedical technical field, and in particular, relates to an indanone compound dual-targeting to tumor cell tubulin and tumor peripheral blood vessels, and a synthetic method and an application thereof. The indanone compound is designed and synthesized. The compound can be combined with tubulin of tumor cells, promotes the tubulin aggregation, disturbs the tubulin depolymerization, thereby disturbing a tumor cell mitosis process; a tumor blood vessel area can be destroyed through the action of the compound with tumor blood vessel endothelial cells. A lot of experiments confirm that through dual-targeting to the tumor cell tubulin and the tumor peripheral blood vessels, the compound can safely and effectively inhibit tumor cell proliferation, promote tumor cell apoptosis, inhibit tumor cell metastasis and inhibit tumor cell angiogenesis. The compound is small in molecular mass, relatively high in oral bioavailability, and relatively flexible in clinical medication, can dual-target to ovarian cancer cells and the peripheral blood vessels thereof, is higher in antitumor activity, and has more advantages in the clinical application.

The present invention provides compounds of Formula (I), compositions comprising an effective amount of a compound of Formula (I), optionally with chemotherapeutic drugs such as a tubulin-binding drug, and methods of their use for reducing the toxicity of cytotoxic agents, treating or preventing cancer or a neuropathic disorder, inducing a chemoprotective phase II enzyme, DNA, or protein synthesis, enhancing the immune system, treating inflammation, improving and enhancing general health or well-being, and methods for making compounds of Formula (I).

A method for detecting an interaction between one or more protein bait and one or more candidate prey in a eukaryotic cell, comprising the steps of: a) providing an eukaryotic cell expressing (i) one or more protein bait, and (ii) one or more candidate prey, wherein said protein bait comprises a bait moiety and a polymerized-tubulin binding moiety. b) determining the occurence of an interaction between said one or more protein bait and said one or more candidate prey in the eukaryotic cell, wherein said protein bait is bound to polymerized tubulin in the eukaryotic cell, thereby localizing said one or more candidate prey along said polymerized tubulin, thereby detecting said interaction.