Lexibulin(CYT-997) is a potent tubulin polymerisation inhibitor with IC50 of 10-100 nM in cancer cell lines; with potent cytotoxic and vascular disrupting activity in vitro and in vivo.IC50 value: 10-100 nM(cell assay) [1]Target: tubulin polymerisation inhibitor in vitro: CYT997 prevented the in vitro polymerization of tubulin with an IC50 of ～3 μmol/L (compared with the half-maximal inhibitory concentration of 2 μmol/L for colchicine under identical conditions) as determined using the conventional turbidimetric assay for tubulin polymerization. CYT997 was also capable of reversibly disrupting the microtubule network in cells, visualized using fluorescence microscopy. Thus, treatment of A549 cells with CYT997 (1 μmol/L) lead to the rapid reorganization of microtubules, including the destruction of the existing microtubule network and accumulation of tubulin in plaques within the cytoplasm of some cells. After 24 hours, major alterations in cell morphology were evident, including loss of adhesion and cell rounding. The effect of 1 hour of treatment with CYT997 was reversible and cells rapidly recovered their normal microtubule architecture. Taken together, the data indicates that CYT997 belongs to the class of anticancer agents that disrupt, rather than stabilize, tubulin-containing structures. Although vehicle-treated cells show 15% and 19% in G2-M phase at 15 and 24 hours (respectively), cells treated with CYT997 (1 μmol/L) had 38% and 43% of cells in G2-M at the same time points. Furthermore, at 24 hours post-CYT997 treatment, only 66% of total cells were in the G1, S, and G2-M phases, which suggests that cells blocked at the G2-M boundary do not exit back to G1, as in the normal cell cycle, but most likely are driven towards apoptosis and cell death [1]. Consistent with the disruption of cellular tubulin, CYT997 potently inhibits proliferation, induces cell cycle arrest and most importantly apoptosis of both human myeloma cell lines (HMCLs) and primary MM cells [2].in vivo: In a xenograft model using the human prostate cancer cell line PC3, oral dosing of CYT997 was initiated 13 days after cell implantation by which time palpable tumors were evident. A dose-dependent inhibition of tumor growth was apparent with CYT997, which at the highest dose was equivalent to parenterally administered paclitaxel. A single dose of CYT997 (7.5 mg/kg i.p.) clearly decreased blood flow in liver metastases, and a significant reduction in blood flow was present 6 hours postdose [1]. CYT997 treatment (15 mg/kg/day) significantly prolongs the survival in a murine model of aggressive systemic myelomatosis [2].
DM4-SPDP is a drug-linker conjugate composed of a potent antitubulin agent DM4 and a linker SMCC to make antibody drug conjugate[1]. SPDP is a short-chain crosslinker for amine-to-sulfhydryl conjugation via NHS-ester and pyridyldithiol reactive groups that form cleavable (reducible) disulfide bonds with cysteine sulfhydryls[2][3].
Moroidin (1) is a bicyclic octapeptide belonging to the Urticaceae-type cyclopeptide family. Moroidin (1) has a potent inhibitory effect on purified tubulin polymerization. Moroidin (1) has cytotoxic effects for several cancer cells, and can induce apoptosis in A549 human lung cancer cells[1].
Compounds 17O (ic50= 14.0 nm, NCI-H460) and 17p (ic50= 2.9 nm, NCI-H460) and furan groups showed effective cytotoxic activity against various human cancer cell lines at the nanomolar level.
Tubulin inhibitor 6 (Compound 14b) is a tubulin inhibitor and a potent inhibitor of multiple cancer cell lines. Tubulin inhibitor 6 inhibits tubulin polymerization with an IC50 of 0.87 μM. Tubulin inhibitor 6 inhibits K562 cell growth with an IC50 of 840 nM[1].
Maytansinol inhibits microtubule assembly and induces microtubule disassembly in vitro.Target: Microtubule/Tubulinin vitro: Maytansinol disrupts the mitotic spindle and prevents mitotic exit in Drosophila. Maytansinol reduces the growth and/or survival of HCT116 cells in a dose-dependent manner and that the effect was more severe for p53+/+ than for p53-/- cells at both low and high doses. Maytansinol inhibits the growth of HCT116 human colon cancer cells. Maytansinol induces apoptosis in imaginal discs of wild-type larvae but not p53 mutant larvae. This parallels the finding in human HCT116 cells, in which Maytansinol was more effective when p53 was present, at least at some doses. Maytansinol induces apoptosis in imaginal discs of wild-type larvae but not p53 mutant larvae at 24 hours after exposure to drug.
MC-betaglucuronide-MMAE-1 is a drug-linker conjugate for ADC with potent antitumor activity by using MMAE (a tubulin polymerization inhibitor), linked via the cleavable ADC linker MC-betaglucuronide.
isoCA-4, a Combretastatin A4 derivative, is a tubulin polymerization inhibitor. isoCA-4 has anti-proliferative activities[1].
Curvulin, isolated from Curvularia lunata, is a phytotoxin[1]. Curvularin is reported to inhibit microtubule assembly and has also been shown to inhibit iNOS expression.
MMAF (Monomethylauristatin F) is an antitubulin agent that inhibit cell division; inhibits H3397 cell growth with an IC50 of 105 nM.
P34cdc2 Kinase Fragment is associated with the completion of DNA replication in yeast mitosis. P34cdc2 Kinase can phosphorylate mitogen-activated protein 2 (MAP2) to regulate microtubules polymerization in Xenopus oocytes meiosis[1][2].
Avanbulin (BAL27862) is a potent, Colchicine site-binding, tubulin assembly inhibitor. Avanbulin inhibits tubulin assembly at 37 °C with an IC50 of 1.4 μM. Avanbulin binds to tubulin with an apparent Kd value of 244 nM. Avanbulin can be used for the research of cancer and cell division[1][2][3][4].
Vinflunine Tartrat is a new vinca alkaloid uniquely fluorinated with the properties of mitotic-arresting and tubulin-interacting activity.Target: Microtubule/TubulinThe major effects of Vinflunine on dynamic instability are a slowing of the microtubule growth rate, an increase in growth duration, and a reduction in shortening duration. The effects of Vinflunine on the readmilling rate is examined by following [3H]GTP incorporation into MAP-rich microtubules, and the IC50 is 0.42 μM [1]. Vinflunine induced mitotic accumulation with IC50 with 18.8 nM, which decreases the centromere dynamicity by 44% and increases the time centromeres spent ina paused state by 63% [2]. Treatment of Vinflunine induces a rapid change in endothelial cell shape: cells retracts and assumes a rounded morphology. Mean IC50 values are 9.9 × 10-5 M × 10-5 M for fibronectin and 5.0× 10-5 M × 10-5 M for type IV collagen. A short 4 hours exposure of endothelial cells to Vinflunine at 10-8 0.05). An ID50 value (dose which inhibits 50% of bFGF-induced neovascularisation) is calculated as 1 mg/kg. Low doses of Vinflunine reduce the number of experimental liver metastases by human LS174T colon cancer cell. A slight overall decrease in liver metastatic foci is already observed at the very low dose of 0.16 mg/kg Vinflunine, although maximal overall inhibition is reached at the maximal tolerated dose (MTD) of 20 mg/kg [3].
Tubulin polymerization-IN-17 (compound 23g) is a potent inhibitor of tubulin polymerization. Tubulin polymerization-IN-17 exhibits tubulin depolymerization and induced cell apoptosis and inhibits migration. Tubulin polymerization-IN-17 has the potential for the research of cancer diseases[1].
CCB02 is a selective CPAP-tubulin interaction inhibitor, binding to tubulin and competing for the CPAP binding site of β-tubulin, with an IC50 of 689 nM, and shows potent anti-tumor activity. CCB02 shows no inhibition on the cell cycle- and centrosome-related kinases, or the phosphorylation status of Aurora A, Plk1, Plk2, CDK2, and CHK1[1].
Glochidiol is an orally active tubulin polymerization inhibitor with an IC50 of 2.76 μM. Glochidiol shows anti-cancer activity[1].
αβ-Tubulin-IN-1 is a potent and orally active αβ-Tubulin inhibitor. αβ-Tubulin-IN-1 induces cell cycle arrest at G2/M and efficient apoptosis. αβ-Tubulin-IN-1 inhibits tumor cell migration and Metastasis. αβ-Tubulin-IN-1 shows significant antitumor efficacy in a dose dependent manner[1].
Microtubule inhibitor 4 (compound 2) is a potent microtubule inhibitor. Microtubule inhibitor 4 shows cytotoxicity with IC50s of 4.0, 3.2, 2.1 nM for NCI-H460, BxPC-3, HT-29 cells, respectively. Microtubule inhibitor 4 shows the inhibition of tubulin polymerization[1].
Tubulin polymerization-IN-21 (compound 9a) is a tubulin polymerization inhibitor. Tubulin polymerization-IN-21 exhibits anti-cancer activity through disrupting cellular integrity and affecting glucose metabolism[1].
Lexibulin 2Hcl (CYT-997 2Hcl) is a potent tubulin polymerisation inhibitor with IC50 of 10-100 nM in cancer cell lines; with potent cytotoxic and vascular disrupting activity in vitro and in vivo.IC50 value: 10-100 nM(cell assay) [1]Target: tubulin polymerisation inhibitor in vitro: CYT997 prevented the in vitro polymerization of tubulin with an IC50 of ～3 μmol/L (compared with the half-maximal inhibitory concentration of 2 μmol/L for colchicine under identical conditions) as determined using the conventional turbidimetric assay for tubulin polymerization. CYT997 was also capable of reversibly disrupting the microtubule network in cells, visualized using fluorescence microscopy. Thus, treatment of A549 cells with CYT997 (1 μmol/L) lead to the rapid reorganization of microtubules, including the destruction of the existing microtubule network and accumulation of tubulin in plaques within the cytoplasm of some cells. After 24 hours, major alterations in cell morphology were evident, including loss of adhesion and cell rounding. The effect of 1 hour of treatment with CYT997 was reversible and cells rapidly recovered their normal microtubule architecture. Taken together, the data indicates that CYT997 belongs to the class of anticancer agents that disrupt, rather than stabilize, tubulin-containing structures. Although vehicle-treated cells show 15% and 19% in G2-M phase at 15 and 24 hours (respectively), cells treated with CYT997 (1 μmol/L) had 38% and 43% of cells in G2-M at the same time points. Furthermore, at 24 hours post-CYT997 treatment, only 66% of total cells were in the G1, S, and G2-M phases, which suggests that cells blocked at the G2-M boundary do not exit back to G1, as in the normal cell cycle, but most likely are driven towards apoptosis and cell death [1]. Consistent with the disruption of cellular tubulin, CYT997 potently inhibits proliferation, induces cell cycle arrest and most importantly apoptosis of both human myeloma cell lines (HMCLs) and primary MM cells [2].in vivo: In a xenograft model using the human prostate cancer cell line PC3, oral dosing of CYT997 was initiated 13 days after cell implantation by which time palpable tumors were evident. A dose-dependent inhibition of tumor growth was apparent with CYT997, which at the highest dose was equivalent to parenterally administered paclitaxel. A single dose of CYT997 (7.5 mg/kg i.p.) clearly decreased blood flow in liver metastases, and a significant reduction in blood flow was present 6 hours postdose [1]. CYT997 treatment (15 mg/kg/day) significantly prolongs the survival in a murine model of aggressive systemic myelomatosis [2].
Vinorelbine (ditartrate) is an anti-mitotic agent which inhibits the proliferation of Hela cells with IC50 of 1.25 nM.
Sovilnesib is a kinesin-like protein KIF18A inhibitor (WO2020132648). Sovilnesib can be used for the research of cancer[1].
3,3'-Diethyl-9-methylthiacarbocyanine iodide is a cyanine dye, also a tau aggregation inhibitor, with an IC50 value of 0.28 μM for tau. 3,3'-Diethyl-9-methylthiacarbocyanine iodide can cause misfunction of the microtubule cytoskeleton. 3,3'-Diethyl-9-methylthiacarbocyanine iodide can be used for researching Alzheimer’s disease[1].
IQTub4P is a potent microtubule (MT) inhibitor. IQTub4P has the cytotoxicity in in HeLa cells, with EC50 of 170 nM. IQTub4P inhibits microtubule structure and function. IQTub4P is well-tolerated in vivo[1].
20-O-Demethyl-AP3 is a minor metabolite of Ansamitocin P-3. Ansamitocin P-3, a microtubule inhibitor, is a macrocyclic antitumor antibiotic[1].
Epothilone B is a microtubule stabilizer with a Ki of 0.71μM. It acts by binding to the αβ-tubulin heterodimer subunit which causes decreasing of αβ-tubulin dissociation.
Batabulin (T138067) is an antitumor agent, which binds covalently and selectively to a subset of the β-tubulin isotypes, thereby disrupting microtubule polymerization. Batabulin affects cell morphology and leads to cell-cycle arrest ultimately induce apoptotic cell death. Batabulin has efficacy against multidrug-resistant (MDR) tumors[1].
MMAD is a potent tubulin inhibitor, is a toxin payload in antibody drug conjugates (ADCs).
Docetaxel is an antineoplastic drug by inhibiting microtubule depolymerization, and attenuating of the effects of bcl-2 and bcl-xL gene expression.
MC-EVCit-PAB-MMAE (Linker-Payload 11) is a drug-linker conjugates for ADC. MC-EVCit-PAB-MMAE contains the ADCs linker (MC-EVCit-PAB) and a potent tubulin polymerization inhibitor MMAE (HY-15162)[1].