ABT-751(E 7010) is a novel bioavailable tubulin-binding and antimitotic sulfonamide agent with IC50 of about 1.5 and 3.4 μM in neuroblastoma and non-neuroblastoma cell lines, respectively.IC50 Value: 1.5 μM(neuroblastoma); 3.4 μM(non-neuroblastoma)Target: Microtubule/Tubulinin vitro: ABT-751 shows the selective cytotoxicity with IC50 of 0.6–2.6 μM in neuroblastoma and 0.7–4.6 μM in other solid tumor cell lines. Furthermore, ABT-751 also exhibits a selective effect on dynamic microtubules and spares stable microtubules, accounting for the persistence of acetylated and detyrosinated α-tubulin positive polymerized tubules at the IC90 concentration of ABT-751. in vivo: In Calu-6 xenograft model, ABT-751 as a single agent at 100 and 75 mg/kg/day shows significant antitumor activity, while in combination with cisplatin, ABT-751 shows a dose-dependent enhancement in growth delay. In the HT-29 colon xenograft model, ABT-751 also shows significant antitumor activity as a single agent and produced a dose-dependent enhancement in growth delay In combination with 5-FU. In dogs with lymphoma, ABT-751 exhibits the dose-limiting toxicities that included vomiting, diarrhea, anorexia, or some combination of these with a maximum tolerated dose (MTD) of 350 mg/m2 PO q24h. Furthermore, the mean AUC and Cmax for ABT-751 at the MTD of 350 mg/m2 is 5.55 μg-hour/mL and 0.9 μg/mL, respectively.
Parbendazole is a potent inhibitor of microtubule assembly, destabilizes tubulin, with an EC50 of 8.79 nM, and exhibits a broad-spectrum anthelmintic activity.
Antiproliferative agent-30 (Compound 8g) inhibits tubulin assembly and inhibits FLT3 and Abl1. Antiproliferative agent-30 has vascular-disrupting activity. Antiproliferative agent-30 has broad antiproliferative activities against cancer cell lines (IC50s: 0.054 nM, 0.008 nM, 0.144 nM for HCT-116, K562, MV-4-11 cells respectively). Antiproliferative agent-30 also has anticancer effect against AML with FLT3-ITD-TKD mutation[1].
Valecobulin hydrochloride (CKD-516 hydrochloride) is a valine prodrug of S516 (HY-130233) and a vascular disrupting agent (VDA). Valecobulin hydrochloride is a potent β-tubulin polymerization inhibitor with marked antitumor activity against murine and human solid tumors[1][2].
Antitumor Agent-71 is an antiproliferative activity antitumor agent and against tumor cell lines with IC50 values ranging from 3.98-15.70 μM. Antitumor Agent-71 is an antitumor agent that can inhibit tubulin polymerization.
THK-5105, an arylquinoline derivative, displays high binding affinity to tau fibrils. THK-5105 has high binding affinity to tau protein aggregates and tau-rich Alzheimer disease (AD) brain homogenates. 18F-THK-5105 has the potential to act as a tau imaging PET probe[1].
SSE15206 is a microtubule polymerization inhibitor, with a GI50 of 197 nM in a SRB proliferation assay in HCT116 cells.
Tubulin polymerization-IN-41 is a potent tubulin polymerization inhibitor with the IC50 of 2.61 μM. Tubulin polymerization-IN-41 targets the Colchicine-binding site of tubulin. Tubulin polymerization-IN-41 has anticancer effects[1].
Tubulysin G is a highly cytotoxic peptide isolated from the myxobacterial species Archangium geophyra and Angiococcus disciformis. Tubulysin displays extremely potent cytotoxic activity in mammalian cells, including multidrug-resistant cell lines, with IC50 values in the lower nanomolar range[1]. Tubulysin G is a cytotoxic activity tubulysin which inhibits tubulin polymerization and leads to cell cycle arrest and apoptosis[2].
Verubulin hydrochloride (MPC-6827 hydrochloride) is a blood brain barrier permeable microtubule-disrupting agent, with potent and broad-spectrum in vitro and in vivo cytotoxic activities. Verubulin hydrochloride (MPC-6827 hydrochloride) exhibits potent anticancer activity in human MX-1 breast and other mouse xenograft cancer models. Verubulin hydrochloride (MPC 6827 hydrochloride) is a promising candidate for the treatment of multiple cancer types[1][2].
Vinorelbine is an anti-mitotic agent which inhibits the proliferation of Hela cells with IC50 of 1.25 nM.
MC-Val-Cit-PAB-MMAF is a drug-linker conjugate for ADC with antitumor activity by using the tubulin inhibitor, MMAF, linked via cathepsin cleavable MC-Val-Cit-PAB.
A novel potent and metabolically stable tubulin inhibitor that can circumvent the drug efflux pumps responsible for multidrug resistance of existing tubulin inhibitors; demonstrates cytotoxicty in a panel of human metastatic melanoma cell lines harboring major clinically relevant mutations with IC50 of 7-10 nM, disrupts microtubule networks, suppresses anchorage-dependent melanoma colony formation, and impaires cancer cell migration; inhibits tumor growth and reduced lung metastasis in melanoma-bearing mice, also completely inhibits tumor growth in a paclitaxel-resistant xenograft mouse model.
Fosbretabulin disodium(CA 4DP; CA 4P) is a microtubule destabilizing drug, a type of vascular-targeting agent, a drug designed to damage the vasculature (blood vessels) of cancer tumors causing central necrosis.IC50 Value: 4 nM [1]Target: microtubulein vitro: Cytotoxic IC(50) values of CA-4 in human bladder cancer cells were below 4 nM. Analyses of cell-cycle distribution showed CA-4 obviously induced G(2)-M phase arrest with sub-G(1) formation. The analyses of apoptosis showed that CA-4 induced caspase-3 activation and decreased BubR1 and Bub3 in cancer cells [1]. The enhanced apoptosis induced by dasatinib plus CA-4 was accompanied by a greater extent of mitochondrial depolarization, caspase-3 activation and PARP cleavage in HO-8910 cells. Furthermore, elevated expression of Mcl-1 led to a reduced apoptosis induced by dasatinib plus CA-4, highlighting that downregulated Mcl-1 was necessary for the potentiating effect of dasatinib to CA-4-triggered apoptosis [2].in vivo: The increased anticancer efficacy of dasatinib combined with CA-4 was further validated in a human HO-8910 ovarian cancer xenograft model in nude mice [2]. There was a significant, concentration dependent increase in mean arterial blood pressure with a maximum increase of about 60% of the baseline MAP at 30 mg/kg of CA4P compared to the saline control. However, there was no significant increase in the cardiac troponin I level after CA4P injection [3].Clinical trial: A phase II trial of fosbretabulin in advanced anaplastic thyroid carcinoma and correlation of baseline serum-soluble intracellular adhesion molecule-1 with outcome [4].
DM4-SMe is a metabolite of antibody-maytansin conjugates (AMCs) and a tubulin inhibitor, and also a cytotoxic moiety of antibody-drug conjugates (ADCs), which can be linked to antibody through disulfide bond or stable thioether bond. DM4-SMe inhibits KB cells with an IC50 of 0.026 nM[1][2].
Tubulin polymerization-IN-10 is a potent tubulin polymerization inhibitor with an IC50 of 4.25±0.75 μM. Tubulin polymerization-IN-10 has anti-tumor effects[1].
Vincristine sulfate is an antitumor vinca alkaloid which inhibits microtubule formation in mitotic spindle, resulting in an arrest of dividing cells at the metaphase stage. It binds to microtubule with a Ki of 85 nM.
DM4 is is an antitubulin agent that inhibit cell division. DM4 can be used in the preparation of antibody drug conjugate.
Vat-Cit-PAB-Monomethyl Dolastatin 10 is a drug-linker conjugate for ADC with potent antitumor activity by using Monomethyl Dolastatin 10 (a potent tubulin inhibitor), linked via the ADC linker Vat-Cit-PAB.
MPT0B014 is a tubulin polymerization inhibitor. MPT0B014 induces cancer cell apoptosis. MPT0B014 can be used for the research of cancer[1].
Tubulin polymerization-IN-20 (compound 11) is a potent inhibitor of tubulin polymerization. Tubulin polymerization-IN-20 has the potential for the research of breast cancers and chemoresistant colon cancers[1].
Combretastatin A4 is a microtubule-targeting agent that binds β-tubulin with Kd of 0.4 μM.
Tubulysin H is a highly cytotoxic peptide isolated from the myxobacterial species Archangium geophyra and Angiococcus disciformis[1]. Tubulysin displays extremely potent cytotoxic activity in mammalian cells, including multidrug-resistant cell lines, with IC50 values in the lower nanomolar range[2]. Tubulysin H is a cytotoxic activity tubulysin which inhibits tubulin polymerization and leads to cell cycle arrest and apoptosis[3].
Polatuzumab vedotin is an antibody-drug conjugate targeting CD79b. It contains a humanized anti-CD79b IgG1 monoclonal antibody linked to monomethyl auristatin E (MMAE), a potent microtubule inhibitor. Polatuzumab vedotin has the potential for the research of Large B-cell lymphomas (LBCL)[1].
3-(3-Phenoxybenzyl)amino-β-carboline is a potent tubulin inhibitor. 3-(3-Phenoxybenzyl)amino-β-carboline promotes selective degradation of αβ-tubulin heterodimers. 3-(3-Phenoxybenzyl)amino-β-carboline induces G2/M phase cell cycle arrest and apoptosis. 3-(3-Phenoxybenzyl)amino-β-carboline exhibits anticancer activity[1].
Davunetide is an eight amino acid snippet derived from activity-dependent neuroprotective protein (ADNP), a neurotrophic factor that exists in the mammalian CNS. Davunetide possesses neuroprotective, neurotrophic and cognitive protective roperties. Davunetide, a microtubule-stabilizing peptide, interacts with and stabilises neuron-specific βIII-tubulin in vitro. Davunetide penetrates the blood-brain barrier and is non-toxic. Davunetide inhibits Aβ aggregation and Aβ-induced neurotoxicity[1][2][3].
Microtubule inhibitor 6 (compound 17o) is a potent microtubule inhibitor. Microtubule inhibitor 6 shows cytotoxicity with IC50s of 14.0, 6.6, 7.0 nM for NCI-H460, BxPC-3, HT-29 cells, respectively. Microtubule inhibitor 6 efficiently inhibits microtubule polymerization[1].
Deoxypodophyllotoxin (DPT), a derivative of podophyllotoxin, is a lignan with potent antimitotic, anti-inflammatory and antiviral properties isolated from rhizomes of Sinopodophullumhexandrum (Berberidaceae). Deoxypodophyllotoxin, targets the microtubule, has a major impact in oncology not only as anti-mitotics but also as potent inhibitors of angiogenesis[1]. Deoxypodophyllotoxin induces cell autophagy and apoptosis[2]. Deoxypodophyllotoxin evokes increase of intracellular Ca2+ concentrations in DRG neurons[3].
KX2-391 (dihydrochloride) is an inhibitor of Src that targets the peptide substrate site of Src, with GI50 of 9-60 nM in cancer cell lines.
Ombrabulin is a derivative of CA-4 phosphate, which is known to exhibit antivascular effects through selective disruption of the tubulin cytoskeleton of endothelial cells.