Vinblastine sulfate is a cytotoxic alkaloid used against various cancer types. Vinblastine sulfate inhibits the formation of microtubule and suppresses nAChR with an IC50 of 8.9 μM.
THK-5117, an arylquinoline derivative, displays high binding affinity to tau fibrils with a Ki of 10.5 nM. THK-5117 has high binding affinity to tau protein aggregates and tau-rich Alzheimer disease (AD) brain homogenates. 18F-THK-5117 has the potential to act as a tau imaging PET probe[1].
Vinflunine ditartrate is the first fluorinated microtubule inhibitor belonging to the Vinca alkaloids family. Vinflunine ditartrate has anti-angiogenic, vascular-disrupting and anti-metastatic activities. Vinflunine ditartrate can be used for the research of transitional cell carcinoma of the urothelial tract, non-small cell lung cancer, and carcinoma of the breast[1][2].
EAPB 02303 is a microtubule-disrupting agent and inhibitor. EAPB 02303 induces mitosis arrest and impairment of spindle assembly. Thus, EAPB 02303 induces apoptosis and exhibits antitumor activity. EAPB 02303 also exhibits a potent synergy with Paclitaxel (HY-B0015) at lower concentrations[1].
Taltobulin (HTI-286; SPA-110) is an analogue of Hemiasterlin; potent tubulin inhibitor; ADCs cytotoxin.IC50 value:Target: tubulinin vitro: HTI-286 significantly inhibited proliferation of all three hepatic tumor cell lines (mean IC50 = 2 nmol/L +/- 1 nmol/L) in vitro. Interestingly, no decrease in viable primary human hepatocytes (PHH) was detected under HTI-286 exposure [1]. In all cell lines tested, HTI-286 was a potent inhibitor of proliferation and induced marked increases in apoptosis. Despite similar transcriptomic changes regarding cell death and cell cycle regulating genes after exposure to HTI-286 or docetaxel, array analysis revealed distinct molecular signatures for both compounds [2].in vivo: Intravenous administration of HTI-286 significantly inhibited tumor growth in vivo (rat allograft model) [1]. HTI-286 significantly inhibited growth of PC-3 and LNCaP xenografts and retained potency in PC-3dR tumors. Simultaneous castration plus HTI-286 therapy was superior to sequential treatment in the LNCaP model [2].
Tilavonemab (ABBV-8E12) is a humanised anti-tau antibody that binds amino acids 25-30 near the N-terminal end of the tau protein. Tilavonemab blocks the ability of human and mouse neurons to take up tau aggregates and reduces brain atrophy. Tilavonemab can be used in the study of Alzheimer's disease[1].
Thiocolchicine, a derivative modified in the C Ring of Colchicine (HY-16569) with enhanced biological properties. Thiocolchicine is a potent inhibitor of tubulin polymerization (IC50=2.5 µM) and competitively binds to tubulin with a Ki of 0.7 µM. Thiocolchicine induces cell apoptosis[1][2]. Thiocolchicine can be used as an ADC cytotoxin in ADC technology.
Tubulysin D is one of the most potent derivatives among the tubulysins isolated from the myxobacterial species Archangium geophyra and Angiococcus disciformis. Tubulysin D is a novel tetrapeptide that displays potent antitumor activity and leads to cell cycle arrest and apoptosis by inhibiting tubulin polymerization with an IC50 of 1.7 μM[1]. Tubulysin displays extremely potent cytotoxic activity in mammalian cells, including multidrug-resistant cell lines, with IC50 values in the lower nanomolar range[2].
Taccalonolide B is microtubule stabilizer isolated from Tacca plantaginea, with antitumor activity. Taccalonolide B is effective in vitro against cell lines that overexpress P-glycoprotein (Pgp) and multidrug-resistance protein (MRP7). Taccalonolide B inhibits growth of SK-OV-3 cells with an IC50 of 208 nM[1][2].
Colcemid (Demecolcine), a derivative of colchicine, is a potent mitotic inhibitor[1][2]. Colcemid binds to the protein tubulin and arrest cells in metaphase for karyotyping assays. Colcemid incuces cell apoptosis and can be used for cancer research[2].
Indibulin (ZIO 301) , an orally applicable inhibitor of tubulin assembly, shows potent anticancer activity with a minimal neurotoxicity. Indibulin reduces inter-kinetochoric tension, produces aberrant spindles, activates mitotic checkpoint proteins Mad2 and BubR1, and induces mitotic arrest and apoptosis[1].
Podophyllotoxin is a potent inhibitor of microtubule assembly and DNA topoisomerase II.IC50 Value:Target: Topoisomerase II; Microtubule/TubulinPodophyllotoxin, a kind of non-alkaloid toxin lignan extracted from the roots and rhizomes of Podophyllum plant, has been shown to inhibit the growth of various carcinoma cells. Podophyllotoxin is a natural product that inhibits the polymerization of tubulin and has served as a prototype for the development of diverse antitumor agents in clinical use.
Tubulysin E 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 E is a cytotoxic activity tubulysin which inhibits tubulin polymerization and leads to cell cycle arrest and apoptosis[2].
Taccalonolide A is a microtubule stabilizer, which is a steroid isolated from Tacca chantrieri, with cytotoxic and antimalarial activities[1][2]. Taccalonolide A causes G2-M accumulation, Bcl-2 phosphorylation and initiation of apoptosis[1]. Taccalonolide A is effective in vitro against cell lines that overexpress P-glycoprotein (Pgp) and multidrug resistance protein 7 (MRP7), with an IC50 of 622 nM for SK-OV-3 cells[3].
Tubulin polymerization-IN-30 (compound 6e) is a potent Tubulin polymerization inhibitor. Tubulin polymerization-IN-30 is a colchicine binding site inhibitor. Tubulin polymerization-IN-30 can disrupt intracellular microtubule organization, arrest cell cycle at the G2/M phase. Tubulin polymerization-IN-30 exhibits the high potency against the cancer cell lines including SGC-7901, A549 and HeLa, with IC50 values of 2.16, 2.21, and 0.403 μM[1].
Taltobulin trifluoroacetate (HTI-286; SPA-110) is an analogue of Hemiasterlin; potent tubulin inhibitor; ADCs cytotoxin.IC50 value:Target: tubulinin vitro: HTI-286 significantly inhibited proliferation of all three hepatic tumor cell lines (mean IC50 = 2 nmol/L +/- 1 nmol/L) in vitro. Interestingly, no decrease in viable primary human hepatocytes (PHH) was detected under HTI-286 exposure [1]. In all cell lines tested, HTI-286 was a potent inhibitor of proliferation and induced marked increases in apoptosis. Despite similar transcriptomic changes regarding cell death and cell cycle regulating genes after exposure to HTI-286 or docetaxel, array analysis revealed distinct molecular signatures for both compounds [2].in vivo: Intravenous administration of HTI-286 significantly inhibited tumor growth in vivo (rat allograft model) [1]. HTI-286 significantly inhibited growth of PC-3 and LNCaP xenografts and retained potency in PC-3dR tumors. Simultaneous castration plus HTI-286 therapy was superior to sequential treatment in the LNCaP model [2].
KIF18A-IN-4 is a moderately potent ATP and microtubule (MT) noncompetitive KIF18A inhibitor (IC50=6.16 μM). KIF18A-IN-4 has selectivity against a large panel of mitotic kinesins and kinases, and does not show any direct effects on tubulin assembly. KIF18A-IN-4 exhibits anti-tumor activity[1].
Tubulin polymerization-IN-52 (compound SC23) is a potent tubulin polymerization inhibitor, with an IC50 of 2.9 μM[1].
Sertaconazole (FI7056 free base) is a broad-spectrum topical antifungal agent, exhibits anti-inflammatory activity via activation of a p38-COX-2-PGE2 pathway. Sertaconazole is also a microtubule inhibitor, shows antiproliferative effect, induces apoptosis and autophagy, and can also inhibit the migration of cells[1][2][3][4].
Cryptophycin 1 is a potent cytotoxic antimicrotubule agent which is isolated from Nostoc sp. Cryptophycin 1 can induce cells apoptosis, and exhibits antitumor activity and exceptional antiproliferative potency[1][2][3].
Estramustine phosphate, an estradiol analog, is an orally active antimicrotubule chemotherapy agent. Estramustine phosphate depolymerises microtubules by binding to microtubule associated proteins (MAPs) and/or to tubulin. Estramustine phosphate can interfere mitosis, trigger cell death and induce apoptosis, which can be used for the research of cancer like prostate cancer[1][2][3].
MY-673 is a colchicine binding site inhibitor (CBSI), that inhibits tubulin polymerization. MY-673 inhibits the ERK signaling pathway, which in turn affects SMAD4 protein expression levels in the TGF-β/SMAD pathway. MY-673 inhibited cell proliferation, migration and induced apoptosis in vivo and in vitro[1].
Tubulin polymerization-IN-37 is a tubulin polymerization inhibitor (IC50: 2.3 μΜ). Tubulin polymerization-IN-37 binds to the colchicine site of tubulin and inhibits colchicine binding. Tubulin polymerization-IN-37 can be used in the research of cancers, such as lymphomas[1].
Epothilone E is a related compound of epothilone, which inhibits microtubule protein function and blocks cell division, and has anti-tumor activity[1].
PE859 is a potent inhibitor of both tau and Aβ aggregation with IC50 values of 0.66 and 1.2 μM, respectively.
Tubulin polymerization-IN-36 is a tubulin polymerization inhibitor (IC50: 2.8 μΜ). Tubulin polymerization-IN-36 binds to the colchicine site of tubulin and inhibits colchicine binding. Tubulin polymerization-IN-36 can be used in the research of cancers, such as lymphomas[1].
Alyssin, found in Cruciferous Vegetables, exerts anticancer activity in HepG2 by increasing intracellular reactive oxygen species and tubulin depolymerization[1].
Triclabendazole(CGA89317) is a benzimidazole, it binds to tubulin impairing intracellular transport mechanisms and interferes with protein synthesis.Target: Microtubule/TubulinTriclabendazole treatment produces percentage decreases of the fluke egg output by 15.3%, 4.3% and 36.6%, respectively, in sheep, dairy cows and heifers, these results indicate the presence of TCBZ-resistant Fasciola hepatica in sheep and cattle on this farm [1]. Triclabendazole sulphoxide (50 mg/mL) results in extensive damage to the tegument of triclabendazole-susceptible F. hepatica, whereas triclabendazole-resistant flukes shows only localized and relatively minor disruption of the tegument covering the spines [2].Triclabendazole is metabolized into a number of compounds, depending on the route of administration, plasma levels peak at 18-24 hours (Triclabendazole sulphoxide) and 36-48 hours (Triclabendazole sulphone), neither Triclabendazole nor any toher metabolites can be detected in plasma. Triclabendazole sulphoxide blocks the transport of secretory bodies from the cell body to the tegumental surface, the block occurs at the site of their formation by the Golgi complex in the cell body, in their movement through the cytoplasmic connections to the syncytium, and in their movement from the base to the apex of the syncytium. Triclabendazole binds to the colchicine binding site on the β-tubulin molecule and this has been used at the basis for evaluating the relative acitvity of Triclabendazole [3].
SKLB0565 is a potent tubulin inhibitor. SKLB0565 shows significant anti-proliferative activity against CRC (colorectal carcinoma) cell lines, with IC50 values ranging from 0.012 μM to 0.081 μM. SKLB0565 causes G2/M phase arrest and mitochondria-mediated intrinsic apoptosis. SKLB0565 inhibits cell migration and disrupted the tube formation of HUVECs[1].
Tubulin inhibitor 7 (Compound 33c) is a tubulin inhibitor and a potent inhibitor of multiple cancer cell lines. Tubulin inhibitor 7 inhibits tubulin polymerization with an IC50 of 0.52 μM. Tubulin inhibitor 7 inhibits K562 cell growth with an IC50 of 11 nM[1].