α-tubulin

ACY-241, also known as Citarinostat (ACY241), is a potent, selective and orally available histone deacetylase (HDAC) inhibitor, with potential antineoplastic activity. Upon oral administration, ACY-241 inhibits the activity of HDACs; this results in an accumulation of highly acetylated chromatin histones, the induction of chromatin remodeling and an altered pattern of gene expression. This leads to the inhibition of tumor oncogene transcription, and the selective transcription of tumor suppressor genes, which inhibit tumor cell division and induce tumor cell apoptosis.

Anti-α-Tubulin Antibody, AF555 conjugate, is a mouse-derived monoclonal antibody conjugated with the red fluorescent dye Alexa Fluor 555, designed for the specific detection of tubulin (Ex Em: 554 567 nm) [1].

MPI_5a is an effective and selective inhibitor of HDAC6 (IC50=36 nM). MPI_5a weakly inhibits other HDAC isoforms and it also inhibits acyl-tubulin accumulation in cells (IC50: 210 nM).

AC 7739 is a microtubule protein binding agent with anticancer and antitumor activity that inhibits advanced solid tumors and in situ transplanted tumors.

Vinorelbine ditartrate (KW-2307) is a natural alkaloid and an anti-mitotic agent. Vinorelbine ditartrate has anti-tumor activity, inhibiting cell proliferation and inducing apoptosis.

Fosbretabulin Disodium (CA 4P), a water-soluble prodrug of Combretastatin A4 (CA4), is a microtubule-targeting agent that binds β-tubulin (Kd: 0.4 μM). Fosbretabulin Disodium(Combretastatin A4 disodium phosphate) inhibits the polymerization of tubulin (IC50: 2.4 μM), and also disrupts tumor vasculature.

Cynaropicrin, a sesquiterpene lactone found in artichoke (Cynara scolymus), has anti-hepatitis C and trypanosome activity and inhibits NF-κB activation. Cynaropicrin disrupts microtubulin- and c-Myc-related signaling and induces parthanatos-type cell death in multiple myeloma.

Lys-SMCC-DM1 (Lys-Nε-MCC-DM1) is an antibody-drug conjugate (ADC) targeting human epidermal growth factor receptor 2 (HER2). It contains the microtubule polymerization inhibitor DM1 as the active metabolite, which inhibits microtubule polymerization. It is commonly used in breast cancer research.

Verubulin (MPC 6827) is a potent microtubule blocker with cytotoxic and potentially anticancer activity that disrupts newly formed blood vessels in xenografts, and can be used to image microtubules (MTs) using positron emission tomography (PET).

Mertansine is a tubulin inhibitor and an antibody-conjugable maytansinoid alkaloid. The IC50 of Mertansine against HCT-15 and A431 cells is 0.750 and 0.04nM.

Sabizabulin (ABI-231) is a potent, orally bioavailable α- and β-tubulin inhibitor that is active against melanoma and prostate cancer cell lines. Sabizabulin inhibits tumor growth and metastatic phenotypes of cervical cancer cells by targeting HPV E6 and E7 and is also being studied in prostate cancer.

Mebendazole (Mebenvet) is a hedgehog inhibitor, used as an antihelminthic.

Pironetin binds to α-tubulin and is an effective inhibitor of microtubule polymerization. It also has cell cycle arrest and antitumor activity. Pironetin is an α β unsaturated lactone isolated from Streptomyces species.

EpoY (SD-142) is an irreversible inhibitor of the primary brain microtubule-associated tyrosine carboxypeptidase (TCP), a complex formed by vasohibin-1 (VASH1) and small vasohibin-binding protein (SVBP). By inhibiting TCP with an IC50 value of approximately 500 nM, EpoY effectively reduces the levels of detyrosinated α-tubulin, which is crucial for microtubule dynamics and neuronal differentiation. This inhibition results in significant differentiation defects and is linked to potential issues related to cancer and cardiomyopathy.

HDAC-IN-82 (Compound 18b) is a histone deacetylase (HDAC) inhibitor that demonstrates selective antimalarial and anticancer activities. It shows significant antiproliferative and caspase3 7 activity in tumor cells. Additionally, HDAC-IN-82 induces hyperacetylation of histone H3 and α-tubulin.

PROTACHDAC6 degrader 3 (Compound 4) is a selective inhibitor and degrader of HDAC6, with an IC50 of 686 nM and a DC50 of 171 nM. It enhances the acetylation of α-tubulin. [Pink: ligand for target protein; Blue: ligand for E3ligaseVHL.]

EGFR-IN-144 (Compound 4B) inhibits EGFR (IC50=0.639 µg mL) and tubulin polymerization (IC50=7.339 µg mL). It exhibits cytotoxicity in various cancer cells with a GI50 at the nanomolar level. EGFR-IN-144 reduces the expression of mTOR, TNF-α, and IL-6, causes G1 S phase cell cycle arrest, and induces apoptosis.

WAY-118959-A (GM-90257) is a competitive inhibitor of αTAT1 (α-tubulin acetyltransferase 1) that directly binds to α-tubulin and inhibits microtubule acetylation, attenuates tumor growth in vivo and induces apoptosis of MDA-MB-231.

HDAC1-IN-5, a potent inhibitor of HDAC1 with an IC50 value of 15 nM, also exhibits inhibitory activity towards HDAC6 with an IC50 value of 20 nM. In cancer cells, HDAC1-IN-5 enhances the acetylation of both histone H3 and α-tubulin, leading to the activation of caspase 3 and induction of apoptosis. Additionally, HDAC1-IN-5 binds with DNA, causing chromatin damage. Furthermore, it demonstrated strong inhibitory activity against tumor growth in xenograft mice. [1]

BRD73954, an effective and specific HDAC inhibitor, which is with IC50 of 36 nM and 120 nM for HDAC6 and HDAC8, respectively.

Antitubulin Agents-1, an antitubulin agent, disrupts microtubules (Microtubule Tubulin) and enhances α-tubulin acetylation, exhibiting anticancer effects.

HDAC3 6-IN-2 (compound 15) is a dual inhibitor targeting HDAC6 and HDAC3, with IC50 values of 0.368 μM and 0.635 μM, respectively. This compound demonstrates antitumor effects by inducing apoptosis in cancer cells, reducing HDAC6 and HDAC3 levels, and increasing acetylation of H3 and α-tubulin [1].

SB26019 is a potent anti-neuroinflammatory compound that modulates the activation of NF-κB by promoting the formation of monomeric α-tubulin, thereby hindering the translocation of p65 and regulating neuroinflammatory processes [1].

HDAC6 degrader-3, a selective and potent degrader of HDAC6 through ternary complex formation and the ubiquitin-proteasome pathway, exhibits a DC50 value of 19.4 nM. With IC50 values of 4.54 nM for HDAC6 and 0.647 μM for HDAC1, it effectively induces robust hyperacetylation of α-tubulin [1].