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.
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].
EMD527040 is a potent and highly selective αvβ6 antagonist with antifibrotic activities. EMD527040 can be used for carcinoma and liver fibrosis research[1].
GLPG0187 is a broad spectrum integrin receptor antagonist with antitumor activity; inhibits αvβ1-integrin with an IC50 of 1.3 nM.
DHA-paclitaxel is an inert prodrug composed of the natural fatty acid DHA covalently linked to the C2'-position of paclitaxel. The paclitaxel moiety binds to tubulin and inhibits the disassembly of microtubules, thereby resulting in the inhibition of cell division. Compared to Paclitaxel, DHA-Paclitaxel targets tumor cells more specifically because tumor cells absorb large amounts of natural fatty acids for use as biochemical precursors and energy sources.
Surfactin is a potent cyclic lipopeptide biosurfactants that mediates flux of mono-and divalent cations, such as calcium, across lipid bilayer membranes. Surfactin can act as an antimicrobial adjuvant with anti-bacterial, anti-fungal, antimycoplasma and hemolytic effects[1][2]. Surfactin also has antiviral activity against a variety of enveloped viruses[3].
Cyclo(Gly-Arg-Gly-Asp-Ser-Pro) (c(GRGDSP)) is an RGD-containing inhibitory peptide. Cyclo(Gly-Arg-Gly-Asp-Ser-Pro) is a synthetic α5β1 integrin ligand that competitively inhibits the binding of invasin (Inv) to α5β1 integrin expressed on Caco-2 cells[1].
Cyclo(Ala-Arg-Gly-Asp-3-aminomethylbenzoyl) is a selective RGD peptide antagonist and has the potential for Pulmonary arterial hypertensionResearch[1].
PF-3758309 is an inhbitor of PAK with IC50 of 1.3 nM for PAK4.
mP6 (Myr-FEEERA-OH) is a myristoylated peptide. mP6 inhibits the interaction of Gα13 with integrin β3 without disrupting talin-dependent integrin function. mP6 can block the GTP usage of Rac1, Rap1, and Rab7, effectively inhibiting the infection of CHO-A24 cells[1].
Plinabulin (NPI-2358) is a vascular disrupting agents (VDA) against tubulin-depolymerizing with IC50 of 9.8~18 nM in tumor cells.IC50 Value: 9.8~18 nMTarget: Microtubule/Tubulinin vitro: NPI-2358 binds to the colchicine-binding site of tubulin and has potent inhibitory to human tumor cell lines which have overexpressed Pgp or reduced nuclear Topo II catalytic activity, with IC50 from 9.8 to 18 nM. NPI-2358 is able to rapidly induce tubulin depolymerization in HUVECs and monolayer permeability even at 20 nM. NPI-2358 induces cell death in MM cells with IC50 of 8-10 nM, which due to trigger early mitotic arrest in MM cells. NPI-2358 also inhibits tubule formation and migration of endothelial as well as MM cells, which leads to disrupt tumor vasculature. NPI-2358 could induces cell death in patient MM (CD138+) cells without effecting viability of normal mononuclear cells. Blockade of JNK abrogates NPI-2358-induced mitotic arrest or MM cell death. in vivo: NPI-2358 (7.5 mg/kg) inhibits tumor growth in human plasmacytoma mouse xenograft models at well-tolerated doses. NPI-2358 induces a time- and dose-dependent decrease in tumour perfusion. NPI-2358 is more sensitive to the KHT sarcoma than the C3H tumour, while radiation response could enhance the antitumor activity in both models.
Eribulin mesylate is a microtubule targeting agent that is used in the treatment of metastatic breast cancer. It inhibits the proliferation of cancer cells by binding microtubule proteins and microtubules.
Tubulin polymerization-IN-9 is a potent tubulin inhibitor with IC50 of 1.82 μM. Tubulin polymerization-IN-9 causes cell cycle arrest at G2/M phase, and induces cell apoptosis and depolarized mitochondria of K562 cells. Tubulin polymerization-IN-9 has potent anti-vascular and antitumor activities[1].
Cepeginterferon alfa-2b is a pegylated interferon. And Cepeginterferon alfa-2b has PEG with molecular weight of 20 kDa as a pegylated base. Cepeginterferon alfa-2b can be used for research of various diseases, such as hepatitis C virus (HCV), polycythemia vera (PV) and essential thrombocythemia (ET)[1][2].
Vc-MMAD consists the ADCs linker(Val-Cit) and potent tubulin inhibitor (MMAD), Vc-MMAD is an antibody drug conjugate.IC50 Valu: N/ATarget: tubulin; ADCsMonomethyl auristatin D (MMAD), a potent tubulin inhibitor, is a toxin payload and antibody drug conjugate.For 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).
BOP sodium is a potent and selective dual α9β1/α4β1 integrin inhibitor with Kd values in the picomolar range. BOP sodium shows the rapid and preferential mobilization of hematopoietic stem cell (HSC) and progenitors. BOP sodium has little inhibitory activity on α4β7, α1β1, α2β1, and α5β1, αIIBβ3 integrins[1][2].
KGDS is synthetic peptides, targeting integrin GPIIb-IIIa located on the membrane of human activated platelets. Amino acid sequence: Lys-Gly-Asp-Ser[1].
Auristatin F is a cytotoxic tubulin modifier with potent and selective antitumor activity; MMAF analog and cytotoxin in Antibody-drug conjugates.
BTB-1 is a potent, selective and reversible mitotic motor protein Kif18A inhibitor with an IC50 of 1.69 μM.
Amphethinile is an anti-tubulin agent. The affinity constant for the association (Ka) of Amphethinile with tubulin is 1.3 μM.
SB-743921 free base is a potent selective inhibitor of the mitotic kinesin KSP (Eg5), with a Ki of 0.1 nM. SB-743921 free base can induce mitotic arrest, block cell cycle progression, induce apoptosis, and can be used in the research of myeloma, leukemia and other diseases[1][2].
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].
5-Aminosalicylic acid acts as a specific PPARγ agonist and also inhibits p21-activated kinase 1 (PAK1) and NF-κB.
Wikstrol A is a potent antifungal, antimitotic and anti-HIV-1 Agent. Wikstrol A induces morphological deformation of P. oryzae mycelia with an MMDC value of 70.1 µM. Wikstrol A shows activity against microtubule polymerization with an IC50 value of 131 µM. Wikstrol A shows anti-HIV-1 activity with an IC50 value of 67.8 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].