Firategrast is an orally bioavailable α4β1/α4β7 integrin antagonist.
Dolastatin 10 is a potent antimitotic peptide, isolated from the marine mollusk Dolabela auricularia, that inhibits tubulin polymerization.
REDV is the minimal active sequence within the CS5 site of the alternatively spliced type III connecting segment (IIICS) region of fibronectin. REDV can mediate adhesion to the IIICS region of plasma fibronectin by binding the integrin alpha 4 beta 1(α4β1). REDV can be used for the research of cell adhesion[1].
2-Methoxyestradiol is an angiogenesis inhibitor and apoptosis inducer with potent antineoplastic activity. 2-Methoxyestradiol also destablize microtubules.
Tubulin polymerization-IN-28 (compound-4) is a microtubule protein polymerization inhibitor with highly selective anticancer activity. Tubulin polymerization-IN-28 can be activated by NQO1 and effectively release combretastatin A-4 to kill tumor cells. Tubulin polymerization-IN-28 can induce cell apoptosis and be used in anti-cancer research[1].
TPI-287, a blood-brain barrier-permeable microtubule stabilizer, can significantly reduce metastatic colonization of breast cancer in the brain[1].
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].
GSK 3008348 (hydrochloride) is a small molecule integrin αvβ6 antagonist, extracted from patent WO/2014154725A1, example 1. The affinity (pIC50) for the human - a 6 protein in the Fluorescence Polarisation Assay for GSK 3008348 (hydrochloride) is 8.1, whereas its affinity in the cell Adhesion Assays was for: ανβ6 (pIC50 = 8.4); ανβ3 (pIC50 = 6); ανβ5 (pIC50 = 6.9); ανβ8 (pIC50 = 7.7).
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].
NVS-PAK1-C is a potent, ATP-competitive and specific allosteric PAK1 inhibitor probe with IC50 values of 5 nM and 6 nM for dephosphorylated PAK1 and phosphorylated PAK1, respectively. NVS-PAK1-C is also against dephosphorylated PAK2 (IC50=270 nM) and phosphorylated PAK2 (IC50=720 nM)[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].
Vedolizumab (anti-α4β7-integrin) is a humanized IgG1 monoclonal antibody that targets the α4β7 integrin for the treatment of ulcerative colitis and Crohn's disease[1][2].
OSU-T315 is an inhibitor of integrin-linked kinase (ILK) with an IC50 of 600 nM.
Auristatin E is a cytotoxic tubulin modifier with potent and selective antitumor activity; MMAE analog and cytotoxin in Antibody-drug conjugates.
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.
Litronesib (Racemate) is the racemate of litronesib. Litronesib is a selective, allosteric inhibitor of Eg5.
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].
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.
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].
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].