α-tubulin acetylation

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

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.

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.]

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]

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].

Sirt1 2-IN-2 (compound hsa55) is a dual inhibitor, targeting SIRT1 with an IC50 of 1.8 μM and SIRT2 with an IC50 of 2.4 μM. It effectively inhibits p53 deacetylation while enhancing the acetylation of p53 and α-tubulin, promoting apoptosis and exhibiting anti-proliferative effects on human leukemia cell lines [1].

Sirt1 2-IN-3 (compound PS9) serves as a dual inhibitor of SIRT1 2, exhibiting IC50 values of 1.4 μM (SIRT1) and 2.0 μM (SIRT2), respectively. This compound effectively inhibits p53 deacetylation while simultaneously elevating p53 and α-tubulin acetylation levels. Additionally, Sirt1 2-IN-3 promotes apoptosis and exhibits antiproliferative effects on human leukemia cell lines [1].

CPTH6, a thiazole derivative, selectively inhibits the lysine acetyltransferase activity of Gcn5 and pCAF without affecting p300 or CBP. It effectively blocks the acetylation of H3/H4 histones and α-tubulin in various leukemia cell lines, leading to reduced cell viability by arresting the cell cycle in the G0/G1 phase and inducing apoptosis. Additionally, CPTH6 disrupts autophagy across several tumor cell lines, primarily by interfering with ATG7-mediated autophagosomal membrane elongation.

HDAC6-IN-34 (compound 21), an orally active, selective HDAC6 inhibitor, exhibits an IC50 of 18 nM. It enhances tubulin acetylation levels without impacting histone acetylation in cutaneous T-cell lymphoma cells and suppresses TNF-α secretion in LPS-stimulated macrophage cells. Furthermore, HDAC6-IN-34 demonstrates outstanding anti-arthritic efficacy in rats [1].