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.

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.

IRC-083927 HCl is novel and potent microtubule inhibitor with potential anticancer activity. IRC-083927 inhibits the tubulin polymerization by a binding to the colchicine site. IRC-083927 inhibits in vitro cell growth of human cancer cell lines in the low nanomolar range. More interesting, it remains highly active against cell lines resistant to microtubule-interacting agents (taxanes, Vinca alkaloids, or epothilones). Chronic oral treatment with IRC-083927 (5 mg kg) inhibits the growth of two human tumor xenografts in nude mice (C33-A, human cervical cancer and MDA-MB-231, human hormone-independent breast cancer). Together, the antitumor effects induced by IRC-083927 on tumor models resistant to tubulin agents support further investigations to fully evaluate its potential for the treatment of advanced cancers, particularly those resistant to current clinically available drugs.

IG-105 is a potent microtubule inhibitor with potential anticancer activity. IG-105 inhibits microtubule assembly by binding at colchicine pocket. IG-105 shows a potent anticancer activity in vitro and in vivo and has good safety in mice. IG-105 showed a potent activity against human leukemia and solid tumors in breast, liver, prostate, lung, skin, colon, and pancreas with IC(50) values between 0.012 and 0.298 mumol L. It was also active in drug-resistant tumor cells and not a P-glycoprotein substrate. It inhibited microtubule assembly followed by M-phase arrest, Bcl-2 inactivation, and then apoptosis through caspase pathways.

Cornigerine is a natural product analog of colchicine produced by Colchicum cornigerum that inhibited tubulin polymerization both with and without microtubule-associated proteins, inhibited the binding of radiolabeled colchicine to tubulin, and stimulated tubulin-dependent GTP hydrolysis.