12 results about "Tubulin polymerization" patented technology

This invention provides a 2-sulfonylpyrimidine-4-amide compound and its uses, belonging to the field of antitumor drug technology. The compound of this invention exhibits excellent antitumor activity targeting the colchicine site of tubulin, demonstrating antiproliferative activity against tumor cells such as HeLa, HepG2, H1299, and MCF-7 at the micromolar level, and significantly inhibiting colony formation in a dose-dependent manner. Furthermore, the compound inhibits tubulin polymerization and disrupts the microtubule network of H1299 cells in vitro, inducing cell cycle arrest in the G2 / M phase and apoptosis. More importantly, the compound can inhibit angiogenesis in HUVECs in vitro. The compound of this invention has great potential in the preparation of microtubule destabilizing agents targeting the colchicine site.

The invention belongs to the technical field of medicines, and relates to an amide compound based on a hydrophobic labeling technology and preparation and application thereof. The structural general formula H of the target product is shown in the specification, or pharmaceutically acceptable salts, solvent compounds or hydrates of the target product. The compound provided by the invention has dual mechanisms of inhibiting polymerization and degradation of tubulin, has an effect of inhibiting tumor proliferation, and has a good prospect in the aspect of development of antitumor drugs.

The present invention relates to a thiobenzimidazole derivative or a pharmaceutically acceptable salt thereof, and a composition for preventing or treating cancer, comprising the derivative as an active ingredient. The thiobenzimidazole derivative of the present invention exhibits cell toxicity by blocking the cell cycle of a cancer cell and inducing apoptosis when administered to an individual, as the derivative inhibits tubulin polymerization by being activated in the cancer cell, and, thus, the derivative can be used for prevention or treatment of cancer, desirably for prevention or treatment of triple-negative breast cancer.

The application belongs to the technical field of biology, and discloses a method for activating an ASXL2-PRC2 axis, wherein adenovirus is injected into the seminiferous tubule of an organism through an outgoing pipe to activate the expression of endogenous EZH2 and spermatocyte-specific ASXL2 in the organism. The method can be used for reducing impaired sperm motility, increasing sperm penetration and tubulin polymerization, inhibiting abnormal spermatogenesis, down-regulating the transcription level of a TZ marker, increasing the enrichment of SUZ12, EED and H3K27me3 in CEP162 and CEP290 promoters under hypoxic conditions, and slowing down hypoxia-induced abnormal spermatogenesis and spermatocyte activation of the ASXL2-PRC2 axis in the germ cell line of the organism.

The present invention relates to a chromene-benzimidazole derivative or a pharmaceutically acceptable salt thereof, and a composition for preventing or treating cancer comprising the derivative as an active ingredient, the chromene-benzimidazole derivative of the present invention being activated in cancer cells, being capable of inhibiting tubulin polymerization and inhibiting a C-terminal domain of Hsp90, and being capable of preventing or treating cancer, or a pharmaceutically acceptable salt thereof, and a composition for preventing or treating cancer comprising the derivative as an active ingredient. When the compound is administered to a subject, cancer cell cycle arrest can be caused to induce cell apoptosis and hinder the activity of onco-protein, and the compound can be used as a novel double-targeting anti-cancer drug to prevent or treat cancers, preferably to prevent or treat triple negative breast cancer.

The invention discloses a colchicine binding site-targeted tubulin inhibitor, the structural general formula of which is selected from one of the following structures: the compound prepared by the invention is the colchicine binding site-targeted tubulin inhibitor, has obvious in-vitro anti-proliferative activity on MCF-7, MDA-MB-231, A549 and Hela tumor cells, and can obviously inhibit the invasion of MCF-7 cells. In addition, the compounds of the present invention inhibit tubulin polymerization in vitro and destroy the microtubule network of MCF-7 cells. In addition, the compound provided by the invention can also enable the mitosis cycle of cells to stop at a G2 / M phase, and induce apoptosis of tumor cells. The compound disclosed by the invention can also remarkably inhibit tumor growth in a mouse body, and has relatively small toxic and side effects.

The invention discloses a CA4 dimer prodrug compound as well as a preparation method and application thereof. The structural formula of the CA4 dimer prodrug compound is shown as a general formula I. The compound disclosed by the invention plays a synergistic anti-tumor role by inhibiting tubulin polymerization and regulating CYP7A1 related pathways; in-vitro experiments show that the IC50 value of the CA4-dimer1 to human liver cancer Hep3B cells is 1.48 + / -0.18 nM, the activity of the CA4-dimer1 is remarkably superior to that of a CA4 monomer, and in animal experiments, the tumor inhibition rate reaches 73.2%, and remarkable hematology and liver and kidney toxicity is not caused; pharmacokinetics shows that the CA4 can be effectively converted into CA4 through intravenous injection, and the anti-tumor effect is achieved; although the CA4 can be released by oral administration; the pharmacokinetic defects and toxic and side effects of CA4 are also effectively improved, and a new strategy is provided for development of anti-liver cancer drugs; .

The present invention relates to: a chromene-benzimidazole derivative or a pharmaceutically acceptable salt thereof; and a composition for preventing or treating cancer, the composition comprising the derivative as an active ingredient. The chromene-benzimidazole derivative according to the present invention is activated in cancer cells to inhibit tubulin polymerization and suppress the C-terminal domain of Hsp90, thereby blocking the cell cycle of cancer cells, inducing apoptosis, and inhibiting the activity of oncoproteins, and thus can be used as a novel dual-target anticancer drug for preventing or treating cancer, preferably for preventing or treating triple-negative breast cancer.

The present invention relates to a quinazoline-benzimidazole derivative or a pharmaceutically acceptable salt thereof, and a composition for preventing or treating cancer comprising the derivative as an active ingredient, the quinazoline-benzimidazole derivative of the present invention being activated in cancer cells, the compound can inhibit tubulin polymerization and tyrosine kinase of a human epidermal growth factor receptor 2 (HER2), can cause cancer cell cycle arrest to induce cell apoptosis and hinder cell growth signals transmitted through the HER2 receptor when being administered to a subject, can be used as a novel double-targeting anti-cancer drug, can prevent or treat cancers, and can be used as a novel anti-cancer drug. Preferably, HER2 positive breast cancer or triple negative breast cancer is prevented or treated.

The present invention relates to a chromene-benzimidazole derivative or a pharmaceutically acceptable salt thereof, and a composition for preventing or treating cancer comprising the derivative as an active ingredient, the chromene-benzimidazole derivative of the present invention being activated in cancer cells, being capable of inhibiting tubulin polymerization and inhibiting a C-terminal domain of Hsp90, and being capable of preventing or treating cancer, or a pharmaceutically acceptable salt thereof, and a composition for preventing or treating cancer comprising the derivative as an active ingredient. When the compound is administered to a subject, cancer cell cycle arrest can be caused to induce cell apoptosis and hinder the activity of protooncoprotein, and the compound can be used as a novel double-targeting anti-cancer drug to prevent or treat cancers, preferably to prevent or treat triple negative breast cancer.

The present invention relates to modulators of canonical-type of transient receptor potential (TRPC) channels and the polymerization of tubulin, compositions thereof, and methods therewith. The present invention also relates to methods of treating TRPC mediated conditions, such as cancer, using such modulators.

The application discloses a benzopentaheterocyclic carboxamide compound or a pharmaceutically acceptable salt thereof and an application thereof, and belongs to the field of medicinal chemistry, and specifically discloses a compound with poly (ADP-ribose) polymerase (PARP) and microtubule protein polymerization double inhibition activity, a structure of the compound is shown as general formula (I). In view of the problems of limited efficacy of existing single-target anti-tumor drugs and drug interaction risks of combined drug use, the compound simultaneously realizes inhibition of PARP and microtubule protein in a single molecule. In-vitro tests show that the compound has good anti-proliferation activity on various tumor cells, and has low toxicity on normal cells; in-vivo xenograft tumor model tests show that the anti-tumor activity of the compound is better than that of a single drug group and a combined drug administration group, meanwhile, the compound does not cause damage to main organs, has good safety, and shows great potential for clinical development as an anti-tumor drug.