32 results about "Tubulin binding" patented technology

A new family of indanone and tetralone tubulin-binding compounds (TBs) is disclosed. Unlike classical TBs, which inhibit mitosis among affected dividing cells, the TBs of the invention possess two unique properties: (1) they induce apoptosis among stationary phase (non-dividing) malignant cells, yet do not impair the viability of normal nonproliferating cells; and, (2) they affect cells which have acquired MDR more powerfully than they affect cells without MDR. Thus, the TBs of the invention provide means to target malignant cells for chemotherapy, even after previous therapies have failed, without affecting normal cells and tissues in the host.

The invention relates to methods for determining resistance or responsivity to microtubule-targeting drug treatment in cancer patients. The methods comprise obtaining a tumor cell sample from a cancer patient and analyzing DNA in the tumor cell sample to determine the presence or absence of a loss of heterozygosity (LOH) at the M40 β-tubulin gene locus within chromosomal locus 6p25, where determining LOH comprises screening for at least one mutation in the M40 β-tubulin gene that affects the binding of a microtubule-targeting drug to β-tubulin. In such methods, the presence of LOH is indicative of microtubule-targeting drug resistance in the cancer patient or of a decreased likelihood that the cancer patient will respond to therapy with a microtubule-targeting drug.

The present invention relates to the use of blood vessel target agent, especially tubulin binding agent, to treat diseases such as eye angiogenesis, eye tumor, diabetic retinopathy, premature retinopathy, retinoblastoma and macular degeneration.

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. Representative analogs include the 9-nitro, 9-bromo-, 9-iodo-, and 9-fluoro-noscapines, which bind tubulin and induce apoptosis selectively in tumor cells (ovarian and T-cell lymphoma) resistant to paclitaxel, vinblastine and teniposide. Surprisingly, treatment with one of the analogs, 9-nitro-nos, at doses as high as 100 μM, did not affect the cell cycle profile of normal human fibroblasts. This selectivity for cancer cells represents a unique edge over the other available antimitotics. The compounds can perturb the progression of cell cycle by mitotic arrest, followed by apoptotic cell death associated with increased caspase-3 activation and appearance of TUNEL-positive cells. Thus, the compounds are novel therapeutic agents for a variety of cancers, including ovarian and T-cell lymphoma cancers, even those that have become drug-resistant to currently available chemotherapeutic drugs.

The present invention relates to the use of vascular targeting agents, especially tubulin-binding agents, for the treatment of eye angiogenesis, eye tumors, diabetic retinopathy, retinopathy of prematurity, retinoblastoma, and macular degeneration.

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 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.

Compositions and methods for treating or preventing infectious diseases, and inhibiting the ability of microbes to travel within mammalian cells, and inhibiting microbial replication, are disclosed. The compositions include various noscapine analogs, which are capable of blocking the movement of viruses and other microbes within mammalian and other cells by inhibiting the cytoplasmic transport mechanisms within the cells. The compositions described herein include an effective amount of the noscapine analogues described herein, along with a pharmaceutically acceptable carrier or excipient. The compositions can also include one or more additional antimicrobial compounds.

Novel tubulin binding compounds and hypoxia activated prodrugs of novel and known tubulin binding compounds useful for treating cancer and other hyperproliferative diseases are disclosed.

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 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 relates to methods for determining the potential of a subject to respond to a particular therapeutic agent, by determining the presence of one or more nucleotide or amino acid variants in the β-tubulin gene or protein. Also provided are methods for treating subjects whose potential to respond to a therapeutic agent has been evaluated. For use in the methods of the invention, there are provided variants of the β-tubulin gene, variants of the β-tubulin protein, nucleic acid molecules and agents which bind to the variant β-tubulin nucleic acid molecules and variant β-tubulin protein, respectively, and kits comprising the same.

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.

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 diagnosis and treatment integrated antitumor drug Caba-808 and a preparation method thereof, the structural formula of the Caba-808 is as shown in formula I as shown in the description, wherein R1 is any one of -H, -CH3 or -CH3CO, and R1 is any one of -C6H5, -NHCOC6H5 or -NHCOOC(CH3)3. The anti-tumor drug Caba-808 provided by the invention can be combined with tubulin to inhibit mitosis of cells, so that an anti-tumor effect is achieved. Meanwhile, the drug has a good fluorescence imaging effect in a near-infrared region, and can clearly display the part and size of a tumor. On the other hand, the preparation method of the novel anti-tumor medicine is simple and easy to operate, and the production cost can be effectively reduced to realize industrial production.