KX2-391 Mesylate is an inhibitor of Src that targets the peptide substrate site of Src, with GI50 of 9-60 nM in cancer cell lines.
Monomethyl auristatin D (MMAD), a potent tubulin inhibitor, is a toxin payload in antibody drug conjugate; Mc-MMAD is a protective group (maleimidocaproyl) -conjugated MMAD.IC50 Value:Target: tubulin; ADCsFor comparison purposes, the ADC A1 -mc-MMAD and/or A1 -vc-MMAD were used. The linker payload, mc-MMAD (6-maleimidocaproyl-monomethylauristatin-D) was conjugated to the A1 anti-5T4 monoclonal antibody through a cysteine residue at a ratio of approximately 4 drug moieties per antibody molecule. The linker payload mc- Val-Cit-PABA-MMAD or vc-MMAD (maleimidocapronic -valine-citruline-p- aminobenzyloxycarbonyl- monomethylauristatin-D) was conjugated to the A1 anti-5T4 monoclonal antibody through a cysteine residue at a ratio of approximately 4 drug moieties per antibody molecule (Antibody-drug conjugates Patent: WO 2013068874 A1).
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].
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].
7-xylosyltaxol(Taxol-7-xyloside) is a taxol (Paclitaxel) derivative; Paclitaxel binds to tubulin and inhibits the disassembly of microtubules.IC50 Value:Target: Microtubule/TubulinPaclitaxel is a compound extracted from the Pacific yew tree with antineoplastic activity. Paclitaxel also induces apoptosis by binding to and blocking the function of the apoptosis inhibitor protein Bcl-2 (B-cell Leukemia 2). Paclitaxel inhibits DNA synthesis and stimulates the release of tumor necrosis factor-α. Paclitaxel induces apoptosis in murine mammary carcinoma MCA-4 and ovarian carcinoma OCA-1 tumors.
Novel irreversible transglutaminase 2 (TG2) inhibitor
Cemadotin (LU103793) is an analogue of Dolastatin 15 (HY-P1126) which is naturally occurring cytotoxic peptides. Cemadotin blocks cells at mitosis, and exhibits Ki value of 1 μM for inhibiting tubulin. Cemadotin can be used to research anticancer[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].
Tubulin inhibitor 24 is a potent tubulin inhibitor. Tubulin inhibitor 24 inhibits tubulin polymerization. Tubulin inhibitor 24 induces cell cycle arrest at the G2/M phase in a concentration-dependent manner. Tubulin inhibitor 24 shows antitumor activity with no obvious toxicity[1].
Thiocolchicine-d3 is deuterium labeled Thiocolchicine. 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.
Tubulin polymerization-IN-15 (compound 4) is a potent inhibitor of tubulin polymerization. Tubulin polymerization-IN-15 has the potential for the research of cancer diseases[1].
PE859 is a potent inhibitor of both tau and Aβ aggregation with IC50 values of 0.66 and 1.2 μM, respectively.
Vinorelbine (ditartrate) is an anti-mitotic agent which inhibits the proliferation of Hela cells with IC50 of 1.25 nM.
Crolibulin is a small molecule tubulin polymerization inhibitor.
Sovilnesib is a kinesin-like protein KIF18A inhibitor (WO2020132648). Sovilnesib can be used for the research of cancer[1].
Myoseverina, a microtubule-binding molecule, induces the reversible fission of multinucleated myotubes into mononucleated fragments. Myoseverina affects the expression of a variety of growth factor, immunomodulatory, extracellular matrix-remodeling, and stress response genes, consistent with the activation of pathways involved in wound healing and tissue regeneration[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].
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].
Tubulin polymerization-IN-56 (compound 8l), an indazole derivative, is a potent tubulin polymerization inhibitor through interacting with the colchicine site, resulting in cell cycle arrest and cellular apoptosis. polymerization-IN-56 reduces cell migration and leads to more potent inhibition of tumor growth in vivo[1].
Podophyllotoxone is isolated from the roots of Dysosma versipellis and has anti-cancer activities.Podophyllotoxone is able to inhibit the tubulin polymerization[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].
Tubulin inhibitor 35 (compound 6b) is a dual inhibitor of topoisomerase I (IC50=~50 μM) and tubulin polymerization (IC50=5.69 μM). Tubulin inhibitor 35 inhibits migration and invasion of MGC-803 and RKO cell lines，and induces apoptosis via arresting cell cycle at G2/M phase. Tubulin inhibitor 35 exhibis potent efficacy in gastrointestinal tumor inhibiton (inhibits MGC-803 (IC50=0.09 μM) and RKO (IC50=0.2 μM) cell lines)[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].
Tubulin polymerization-IN-12 is a tubulin polymerization inhibitor (IC50=0.75 μM). Tubulin polymerization-IN-12 arrests cell cycle at G2/M phase, and exhibits cytotoxicity against cancer cells[1].
Ansamitocin P-3 is a microtubule inhibitor. Ansamitocin P-3 is a macrocyclic antitumor antibiotic.
20-O-Demethyl-AP3 is a minor metabolite of Ansamitocin P-3. Ansamitocin P-3, a microtubule inhibitor, is a macrocyclic antitumor antibiotic[1].