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].
Litronesib (Racemate) is the racemate of litronesib. Litronesib is a selective, allosteric inhibitor of Eg5.
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].
Gardenin A is an orally active and synthetic PMF analogue with the neurotrophic effect for neurite outgrowth and neuronal differentiation. Gardenin A promotes neuritogenesis via activating MAPK/ERK, PKC, and PKA, but not TrkA, CREB signaling pathways. Gardenin A also has sedative, anxiolytic, antidepressant, and anticonvulsant effects[1][2].
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].
TC-Mps1-12 is a potent and selective monopolar spindle 1 (Mps1) inhibitor, with an IC50 of 6.4 nM[1].
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].
RGD Trifluoroacetate is a tripeptide that effectively triggers cell adhesion, addresses certain cell lines and elicits specific cell responses; binds to integrins.
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].
Danicamtiv is a positive inotropic agent.
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.
KIF18A-IN-2 is a potent KIF18A inhibitor (IC50=28 nM). KIF18A-IN-2 causes significant mitotic arrest and increases the number of mitotic cells in tumor tissues. KIF18A-IN-2 can be used for researching cancer[1].
Cucurbitacin B belongs to a class of highly oxidized tetracyclic triterpenoids; could repress cancer cell progression.IC50 value:Target: anticancer natural compoundin vitro: Cucurbitacin-B inhibited growth and modulated expression of cell-cycle regulators in SHSY5Y cells. At the molecular level, we found that Cucurbitacin-B inhibited AKT signaling activation through up-regulation of PTEN [1]. CuB induced apoptosis of A549 cells in a -concentration-dependent manner, as determined by fluorescence microscopy, flow cytometry and transmission electron microscopy. CuB dose-dependently inhibited lung cancer cell proliferation, with cell cycle inhibition and cyclin B1 downregulation. Apoptosis induced by CuB was shown to be associated with cytochrome c release, B-cell lymphoma 2 downregulation and signal transducer and activator of transcription 3 pathway inhibition [2]. CuB inhibited ITGA6 and ITGB4 (integrin α6 and integrin β4), which are overexpressed in breast cancer. Furthermore, CuB also induced the expression of major ITGB1and ITGB3, which are known to cause integrin-mediated cell death [3]. Cuc B treatment caused DNA double-strand breaks (DSBs) without affecting the signal transducer and activator of transcription 3 (STAT3), the potential molecular target for Cuc B. Cuc B triggers ATM-activated Chk1-Cdc25C-Cdk1, which could be reversed by both ATM siRNA and Chk1 siRNA. Cuc B also triggers ATM-activated p53-14-3-3-σ pathways, which could be reversed by ATM siRNA [4].in vivo: Efficacy of CuB was tested in vivo using two different orthotopic models of breast cancer. MDA-MB-231 and 4T-1 cells were injected orthotopically in the mammary fat pad of female athymic nude mice or BALB/c mice respectively. Our results showed that CuB administration inhibited MDA-MB-231 orthotopic tumors by 55%, and 4T-1 tumors by 40%. The 4T-1 cells represent stage IV breast cancer and form very aggressive tumors [3].
Ganoderic acid T-Q (Ganodermic acid T-Q) (compound 1) is a natural product that can be found in ganoderma lucidum. Ganoderic acid T-Q stimulates tubulin polymerization[1].
AZD4877 is another isostere to Ispinesib (HY-50759)and also a kinesin spindle protein (Eg5) inhibitor with IC50 of 2 nM.AZD4877 arrests cell mitosis, leads to the formation of the monopolar spindle phenotype and induces apoptosis. AZD4877 inhibits circulating peripheral blood mononuclear cells (PBMCs) and has anti-cancer activity[1][2][3][4][5].
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].
MK-0731 is a selective, non-competitive and allosteric kinesin spindle protein (KSP) inhibitor with an IC50 of 2.2 nM and a pKa of 7.6. MK-0731 is >20,000 fold selectivity against other kinesins. MK-0731 induces mitotic arrest and induces apoptosis in tumors. MK-0731 provides significant antitumor efficacy[1][2].
FRAX486 is a p21-activated kinase (PAK) inhibitor with IC50s of 14, 33 and 39 nM for PAK1, PAK2 and PAK3, respectively.
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].
st-Ht31 is a membrane-permeable peptide inhibitor of protein kinase A (PKA) anchoring. st-Ht31 induces robust cholesterol/phospholipid efflux. st-Ht31 completely reverses foam cell formation and restores the metabolic health of macrophage[1][2].
ELR510444 is a novel microtubule disruptor; inhibits MDA-MB-231 cell proliferation with IC50 of 30.9 nM; not a substrate for the P-glycoprotein drug transporter and retains activity in βIII-tubulin-overexpressing cell lines.IC50 value: 30.9 nM(MDA-MB-231 cell) [1]Target: Microtubule disruptorELR510444 is not a substrate for the P-glycoprotein drug transporter and retains activity in βIII-tubulin-overexpressing cell lines, suggesting that it circumvents both clinically relevant mechanisms of drug resistance to this class of agents. ELR510444 also shows potent antitumor activity in the MDA-MB-231 xenograft model with at least a 2-fold therapeutic window. Studies in tumor endothelial cells show that a low concentration of ELR510444 (30 nM) rapidly alters endothelial cell shape, similar to the effect of the vascular disrupting agent combretastatin A4. ELR510444 is a novel microtubule-disrupting agent with potential antivascular effects and in vivo antitumor efficacy [1]. ELR510444 decreased HIF-1α and HIF-2α levels, reduced RCC cell viability and clonogenic survival, and induced apoptosis. VHL-deficient RCC cells were more sensitive to ELR510444-mediated apoptosis and restoration of VHL promoted drug resistance. Higher concentrations of ELR51044 promoted apoptosis independently of VHL status, possibly due to the microtubule destabilizing properties of this agent. ELR510444 significantly reduced tumor burden in the 786-O and A498 RCC xenograft models [2].
Orbofiban acetate is an orally active platelet GPIIb/IIIa antagonist that inhibits platelet aggregation.
Cyclo(Arg-Gly-Asp-D-Phe-Val) is an integrin αvβ3 inhibitor. Cyclo(Arg-Gly-Asp-D-Phe-Val) has antitumor activity. Cyclo(Arg-Gly-Asp-D-Phe-Val) can be used for the research of acute myeloid leukemia[1].
Mps1-IN-7 is a potent MPS1 inhibitor (IC50 of 0.020 μM) over JNK1 and JNK2 (JNK1 IC50 = 0.11 μM, JNK2 IC50=0.22 μM). Mps1-IN-7 inhibit SW620, CAL51, Miapaca-2, RMG1 cell growth with GI50 values of 0.065, 0.068, 0.25, and 0.110 μM,respectively[1].
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].
RGD-4C is a arginine-glycine-aspartic acid peptide (ACDCRGDCFC) with integrin binding activity. The Arg-Gly-Asp (RGD) sequence serves as the primary integrin recognition site in extracellular matrix proteins, and peptides containing this sequence can mimic the recognition specificity of the matrix proteins. RGD-4C is a αv-integrin ligand, can conjugate with bioactive molecule to exert antitumor effects in animal models[1][2][3].
TC-I 15 (TC-I-15) is an allosteric, collagen-binding integrin α2β1 inhibitor with IC50 values of 26.8 μM and 0.4 μM for GFOGER and GLOGEN, respectively. TC-I 15 inhibits platelet adhesion to collagen and thrombus deposition[1].
Omecamtiv mecarbil is a cardiac myosin activator.
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].