colchicine-binding

Crolibulin (EPC2407) is an inhibitor of small molecule tubulin polymerization.

Colchicine is an orally active natural alkaloid that acts by inhibiting microtubule polymerization (IC50 = 3 nM) and as a competitive antagonist of the α3 glycine receptor. It possesses broad anti-inflammatory, immunosuppressive, and antifibrotic activities, can inhibit NLRP3 inflammasome activation to prevent NSAID-induced small intestine injury, holds potential for gouty arthritis and rheumatoid arthritis research, and is commonly used to establish Alzheimer’s disease models.

Tartaric acid disodium dihydrate (Disodium L-(＋)-Tartrate Dihydrate) is commonly used as a buffer in molecular biology and cell culture.Tartaric acid disodium dihydrate is an acid phosphatase inhibitor that increases the probability of colchicine binding to tubulin1.

3-Demethylthiocolchicine, a colchicine analog, exhibits broad-spectrum antitumor activity and shares similar properties and activities with colchicine in inhibiting casein-induced amyloidosis, microtubule binding, and anti-inflammatory effects. Notably, it has significantly lower toxicity compared to colchicine.

Tubulin polymerization-IN-70 (compound Q19) is an effective inhibitor of tubulin polymerization. This compound exerts antiproliferative properties by targeting the colchicine binding site on tubulin, thereby inhibiting its polymerization. Tubulin polymerization-IN-70 also induces apoptosis and cell cycle arrest at the G2/M phase. Additionally, it triggers a decrease in mitochondrial membrane potential and elevates levels of reactive oxygen species (ROS). Moreover, Tubulin polymerization-IN-70 possesses anti-angiogenic and anticancer activities.

Tubulin Polymerization-IN-1 prodrug (Compound 2b) is a microtubule polymerization inhibitor prodrug mediated by Pd. Developed from colchicine-binding site inhibitors (CBSIs), it aims to reduce toxicity and enhance targeted release. Compared to the parent compound, its cytotoxicity is decreased by 68.3 times, but can be in situ restored in the presence of Pd resin. Mechanistic studies show it retains the same antitumor activity as CBSIs. In vivo tests demonstrate that, once activated by Pd resin, it significantly suppresses tumor growth (63.2% inhibition rate). Tubulin Polymerization-IN-1 prodrug is a promising candidate for cancer research.

Tubulinpolymerization IN-59 ((R) -9k) is an effective inhibitor of CBSI (colchicine binding site).

Tubulin polymerization-IN-72 (Compound 4a4) is a microtubule synthesis inhibitor with anticancer properties. By binding to the colchicine site, it disrupts the polymerization of tubulin, resulting in the arrest of cancer cells at the G2/M phase and inducing apoptosis (Apoptosis). The IC50 for its activity against cancer cells is 0.4-2.7 nM.

Tubulin polymerization-IN-76 (compound 20b) is a potent and orally active inhibitor of tubulin polymerization. It acts at the colchicine binding site to inhibit tubulin polymerization with an IC50 value of 2.505 μM, effectively disrupting the intracellular microtubule network and interfering with mitosis. Tubulin polymerization-IN-76 shows significant inhibitory effects on MGC-803 and HGC-27 cells, with IC50 values of 1.61 and 1.82 nM, respectively. It effectively suppresses colony formation and cell migration activities in these cell lines, inducing G2/M phase cell cycle arrest and apoptosis (Apoptosis). Furthermore, Tubulin polymerization-IN-76 exhibits broad-spectrum antiproliferative activity.

BKS3031A is an inhibitor of αβ-tubulin that binds to the colchicine binding site, thereby hindering the dynamics of microtubule assembly.

Microtubulin-IN-1 (Compound 8g) is an inhibitor of microtubulin, targeting the colchicine-binding site to disrupt tubulin integrity and induce upregulation of p53 protein expression. It exhibits antiproliferative activity across various cancer cell lines, including NCI-H460, BxPC-3, and HT-29, with IC50 values of 2.4, 1.6, and 2.07 nM, respectively. Additionally, Microtubulin-IN-1 induces cell cycle arrest at the G2/M phase and apoptosis in NCI-H460 cells.

Tubulin/HDAC-IN-4 (compound 9n) is a dual inhibitor targeting microtubules (Tubulin) and HDAC, exhibiting IC50 values of 0.73, 0.43, 0.62, and 2.34 µM for HDAC1, HDAC2, HDAC6, and HDAC7, respectively. It disrupts microtubule assembly by binding to the colchicine site and induces apoptosis and G2/M cell cycle arrest. Additionally, Tubulin/HDAC-IN-4 significantly increases intracellular ROS levels and demonstrates both anti-angiogenic and anticancer properties.

PYRIB-SO 2 is an effective antimitotic (mitotic) agent that exhibits antiproliferative activity and induces cell cycle arrest at the G2/M phase. It disrupts and reduces microtubule structures by binding to the colchicine-binding site (C-BS) on α, β-tubulin.

Tubulin polymerization-IN-64 (Compound 8a) is a microtubule polymerization inhibitor that functions by occupying the colchicine binding site on tubulin, with an IC50 of 6.9 μM. This compound suppresses the proliferation of cancer cell lines A549, HeLa, HCT116, and HT-29, with IC50 values of 2.42, 10.33, 6.28, and 5.33 μM, respectively. Tubulin polymerization-IN-64 induces cell cycle arrest at the G2/M phase and triggers apoptosis in A549 cells.

Tubulin/LSD1-IN-1 is a potent dual inhibitor of tubulin polymerization and LSD1 (IC50 = 1.72 μM), exhibiting broad-spectrum antiproliferative activity against cancer cell lines. By targeting the colchicine binding site, it disrupts the microtubule network in gastric cancer cells. Tubulin/LSD1-IN-1 enhances methylation levels of H3K4me1/2 and H3K9me2/3, facilitating epigenetic regulation. It induces G2/M phase arrest, promotes apoptosis, and effectively inhibits colony formation in gastric cancer cells.

Tubulin polymerization-IN-79 (Compound C20) acts as an inhibitor of microtubule polymerization. It exhibits significant antiproliferative activity against esophageal cancer cells, such as KYSE450 (IC50=0.36 μM) and EC-109 (IC50=0.63 μM). In esophageal cancer cells, Tubulin polymerization-IN-79 occupies the colchicine binding site, disrupting the microtubule network's integrity, activating the Hippo signaling pathway, downregulating the oncogenic protein YAP, and inducing G2/M phase arrest and apoptosis. This compound shows promise for esophageal cancer research.

N-Deacetyl-N-formylcolchicine (N-Formyl-N-deacetylcolchicine, Compound 11) is a selective inhibitor targeting the colchicine binding site on tubulin. It exhibits antiproliferative activity against various cancer cell lines, with IC50 values ranging from 32.61 to 100.28 nM. This compound inhibits microtubule polymerization, blocking cell division, inducing apoptosis in cancer cells, and suppressing cellular migration. N-Deacetyl-N-formylcolchicine shows potential for research in lung cancer and other solid tumors.

RGN6024 is an orally active, reversible small molecule that can penetrate the blood-brain barrier and acts as a microtubule (tubulin) destabilizer. It inhibits microtubule polymerization in both biochemical and cellular assays. RGN6024 binds to the colchicine-binding site of β-tubulin with affinity constants of Kd= 6.7 μM (SPR) and Kd= 7.4 μM (tryptophan assay), inducing G2/M phase arrest in glioblastoma (GB) cells. The compound remains effective in cells overexpressing βIII-tubulin. Additionally, RGN6024 is able to suppress tumor growth in glioblastoma (GB) xenograft mouse models. This compound is applicable for research in glioblastoma (GB).

Tubulin-IN-53 is a potent inhibitor of microtubulin (Tubulin) with an IC50 of 6.06 μM. By targeting the colchicine binding site on tubulin, Tubulin-IN-53 hinders tubulin polymerization, disrupting the microtubule network. It induces cell cycle arrest at the G2/M phase and apoptosis (apoptosis) in MCF-7 cells, while inhibiting cell migration. This compound also leads to a reduction in mitochondrial membrane potential and an increase in reactive oxygen species (ROS) accumulation. Additionally, Tubulin-IN-53 disrupts angiogenesis in human umbilical vein endothelial cells and is applicable in research on cancers such as breast and lung cancer.

Plinabulin (NPI-2358) (NPI-2358) is a vascular disrupting agent (VDA) against tubulin-depolymerizing tumor cells ( IC50: 9.8-18 nM). Plinabulin selectively targets and binds to the colchicine-binding site of tubulin, thereby interrupting equilibrium of microtubule dynamics. This disrupts mitotic spindle assembly leading to cell cycle arrest at M phase and blockage of cell division.

DAT1 is an antimitotic and antiangiogenic that acts by binding to the colchicine binding site of tubulin.

Mivobulin is a tubulin inhibitor potentially for the treatment of glioma, malignant melanoma, prostate, ovarian cancer. CI-980 acts at the colchicine-binding site.

Combretastatin A-1 phosphate (OXi-4503) tetrasodium, a prodrug of Combretastatin A-1, is a tubulin-binding microtubule polymerization inhibitor targeting the colchicine-binding site. By inducing tubulin depolymerization, it inhibits the Wnt/β-catenin pathway and deactivates AKT, possessing both anti-tumor and anti-vascular properties.

Tubulin inhibitor 29 (compound 3c) is a potent tubulin inhibitor that disrupts tubulin assembly by binding at the colchicine site (IC50 = 1.2 μM), and exhibits antiproliferative effects on MCF-7 cells with an IC50 value of 7.5 μM. [1].