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.

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].

Tubulin polymerization-IN-36 is able to be used in cancer research, for example, lymphomas. Tubulin polymerization-IN-36 binds to the colchicine site of tubulin and inhibits colchicine binding, that is an inhibitor of tubulin polymerization with IC50 of 2.8 μΜ[1].

Tubulin polymerization-IN-37 is a potent inhibitor (IC50: 2.3 µM) of tubulin polymerization, binding specifically to the colchicine site of tubulin and preventing colchicine binding, with potential applications in cancer research, notably for lymphomas [1].

MY-875 is a potent microtubulin polymerization inhibitor that competes at colchicine binding sites, exhibiting an IC50 value of 0.92 μM. It effectively suppresses microtubulin polymerization, exerting its inhibitory effect. Additionally, MY-875 exerts its biological impact by activating the Hippo pathway, inducing apoptosis, and displaying commendable anticancer activity [1].

Tubulin polymerization-IN-26 (compound 12h) is a chemical compound that inhibits the polymerization of microtubulin by binding to the colchicine binding site, with an IC50 value of 4.64 μM. It can induce apoptosis and inhibit cell metastasis, making it a valuable compound for researching lung cancer [1].

Tubulin Inhibitor 11 is a potent, orally active agent that inhibits tubulin by targeting the Colchicine binding site. It impedes tubulin polymerization, leading to mitotic blockade and apoptosis.