hdac6

HDAC6-IN-6 (compound 6a) is a potent HDAC6 inhibitor with an IC50 value of 0.025 μM that can penetrate the BBB. It exhibits strong inhibitory activity against AChE and Aβ 1-42 self-aggregation with IC50 values of 0.72 and 3.0 μM, respectively. HDAC6-IN-6 also enhances neurite outgrowth without significant neurotoxicity [1].

HDAC6 degrader 9c is a small molecule histone deacetylase 6 (HDAC6) degrader that can be used to study cancer or other diseases.

TCS HDAC6 20b is an HDAC6-selective inhibitor that impedes the growth of estrogen receptor α-positive breast cancer MCF-7 cells [1].

BChE HDAC6-IN-2 is a selective and potent dual inhibitor of BChE and HDAC6 with neuroprotective and reactive oxygen species (ROS) scavenging activity. BChE HDAC6-IN-2 is a metal ion co-agonist that inhibits tau phosphorylation and can be used in the study of immune and neurological diseases.

HDAC6-IN-17 (compound 5b) is a potent HDAC6 inhibitor with IC50 values of 150 nM for HDAC6, 1400 nM for HDAC8, and 2300 nM for HDAC4, demonstrating cytotoxic activity against human cancer cell lines and being utilized in cancer research [1].

HDAC6-IN-19 (Compound 14g), an HDAC6 inhibitor with an IC50 of 2.68 nM, additionally inhibits HDAC1, HDAC2, and HDAC3, with IC50 values of 61.6 nM, 98.7 nM, and 103 nM, respectively. This compound effectively suppresses the proliferation of various cancer cell lines, such as leukemia, colon cancer, melanoma, and breast cancer [1].

HDAC6-IN-5 (compound 11b) is a potent and BBB-penetrated inhibitor of HDAC6 (IC50 = 0.025 μM) that inhibits Aβ 1-42 self-aggregation and AChE with IC50 values of 3.0 and 0.72 μM, respectively. Additionally, HDAC6-IN-5 can enhance neurite outgrowth without significant neurotoxicity.

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].

Compound A6, a potent and selective PROTAC HDAC6 degrader, exhibits a DC50 of 3.5 nM. It demonstrates notable antiproliferative activity by inducing apoptosis in myeloid leukemia cell lines [1].

HDAC6/HSP90-IN-1 is a potent and selective dual inhibitor of HDAC6 (IC50: 4.3 nM) and HSP90 (IC50: 46.8 nM).HDAC6/HSP90-IN-1 downregulates PD-L1 expression in INF-γ-treated H1975 lung cancer cells.HDAC6/HSP90-IN-1 exhibits tumor growth inhibition in H1975 xenograft mice.HDAC6/HSP90-IN-1 is a potent and selective dual inhibitor of HDAC6 (IC50: 4.3 nM) and HSP90 (IC50: 46.8 nM). 1 exhibited tumor growth inhibition in H1975 xenograft mice.

HDAC6-IN-13 (Compound 35m) is a potent and highly selective orally active inhibitor of HDAC6, with an IC50 of 0.019 μM. It also inhibits HDAC1, HDAC2, and HDAC3, with IC50 values of 1.53 μM, 2.06 μM, and 1.03 μM, respectively. HDAC6-IN-13 exhibits substantial blood-brain barrier permeability and anti-inflammatory properties [1].

HDAC6-IN-25 (compound 8) is a potent and selective HDAC6 inhibitor with an IC50 value of 0.6 nM [1].

HDAC6 degrader-1, a proteolysis-targeting chimeric molecule (PROTAC), incorporates the selective HDAC6 inhibitor Nexturastat A (Nex A) for HDAC6 binding, a linker, and an E3 ligase recruiting ligand. This compound effectively induces HDAC6 degradation, displays superior selectivity over other HDAC isoforms, and efficiently inhibits cell proliferation [1].

PI3Kα HDAC6-IN-1 (compound 21j) is a dual inhibitor of PI3Kα and HDAC6, with IC50 values of 2.9 nM and 26 nM, respectively. It hinders AKT(Ser473) phosphorylation and promotes the accumulation of acetylated α-tubulin without affecting acetylated histones H3 and H4. The compound exhibits potent anti-cancer efficacy, inhibiting the L-363 cell line with an IC50 of 0.17 μM [1].

HDAC6-IN-23 (compound 9), an orally active inhibitor of HDAC6 [1], displays selective enzymatic inhibition.

HDAC6-IN-9 (compound 12c) is a potent and selective inhibitor of HDAC6 with anti-proliferative activities, demonstrating IC50 values of 4.2 nM for HDAC6, 11.8 nM for HDAC1, 15.2 nM for HDAC3, 139.6 nM for HDAC8, and 21.3 nM for HDAC10 [1].

HDAC6-IN-15, a selective histone deacetylase 6 (HDAC6) inhibitor, exhibits potent inhibitory activity with an IC50 value of 38.2 nM, making it valuable for research in cancer and neurodegenerative diseases.

HDAC6-IN-21 (compound 13) is an irreversible inhibitor of histone deacetylase 6 (HDAC6) [1].

BChE HDAC6-IN-1 is a dual BChE HDAC6 inhibitor exhibiting potent and selective inhibition with IC50 values of 4 nM for BChE and 8.9 nM for HDAC6. It demonstrates efficacy in alleviating cognitive deficits in an Aβ1–42-induced mouse model, indicating its potential utility in Alzheimer's disease research [1].

HDAC6-IN-18 (Compound 4), an irreversible and selective HDAC6 isoform inhibitor, exhibits potent anti-multiple myeloma effects. It demonstrates HDAC6 inhibitory activity with IC50 values of 0.17, 0.7, and 0.42 μM in RPMI8266, U266, and MM.1S cells, respectively [1].

HDAC6 8 BRPF1-IN-1 is a dual inhibitor targeting HDAC6, HDAC8, and the bromodomain and PHD finger containing protein 1 (BRPF1). It exhibits inhibitory activity against HDAC1, HDAC6, and HDAC8 with IC50 values of 797 nM, 344 nM, and 908 nM, respectively, and inhibits BRPF1 with a Kd value of 175.2 nM. This compound is utilized in cancer research [1].

HDAC6-IN-11 (Compound 9) is a selective HDAC6 inhibitor with an IC50 value of 20.7 nM, demonstrating over 300-fold selectivity against other isoforms [1], and exhibits anti-proliferative activities against cancer cells.

HDAC6-IN-3 (Compound 14) is a potent anti-prostate cancer agent that acts as an orally active inhibitor of HDAC6. It has IC50 values ranging from 0.02-1.54 μM for HDAC1, HDAC2, HDAC3, HDAC6, HDAC8, and HDAC10. Additionally, HDAC6-IN-3 also demonstrates effective inhibition of MAO-A (IC50 = 0.79 μM) and LSD1 [1].

HDAC6-IN-14, an inhibitor of HDAC6 (HDAC), exhibits high selectivity with an IC50 value of 42 nM, demonstrating over 100-fold selectivity compared to HDAC1, HDAC2, HDAC3, and HDAC4.

HDAC6-IN-10 is a potent and specific HDAC6 inhibitor, exhibiting an IC50 value of 0.73 nM. It demonstrates remarkable selectivity towards HDAC6, with a selectivity range of 144 to 10,941-fold over other HDAC isoforms. Furthermore, HDAC6-IN-10 exhibits notable anti-proliferative effects on multiple myeloma cells [1].

HDAC6 HSP90-IN-2 (compound 6e) is a dual inhibitor of HDAC6 and Hsp90 with IC50 values of 105.7 nM and 61 nM, respectively, primarily used in cancer research [1].

HDAC6-IN-12 is a potent inhibitor of HDAC6 that binds in the DNA chain, causing DNA damage and exhibiting anticancer effects that can be used in cancer research.

HDAC6-IN-4 (C10) is an orally active, highly selective HDAC6 inhibitor with an IC50 of 23 nM. It induces apoptosis and demonstrates potent anti-tumor effects while exhibiting non-significant toxicity.

mTOR/HDAC6-IN-1 is an effective dual inhibitor of histone deacetylase (HDAC6) and mammalian rapamycin (mTOR). The IC50 values for HDAC6 and mTOR are 56 nM and 133.7 nM respectively. MTOR/HDAC6-IN-1 can significantly induce autophagy and apoptosis and inhibit migration. MTOR/HDAC6-IN-1 has potential in the study of triple negative breast cancer (TNBC).

HDAC6-IN-24 (compound N1) is an inhibitor of histone deacetylase 6 (HDAC6) [1].

HDAC6-IN-16 (compound 5c), a quinazolin-4(3H)-one-based inhibitor of histone deacetylase 6 (HDAC6), demonstrates an anticancer effect by inhibiting colony formation, arresting the cell cycle at the G2 phase, and inducing apoptosis [1].

HDAC6-IN-22 (compound 30), an HDAC6 inhibitor, exhibits an IC50 of 4.63 nM and demonstrates antiproliferative effects against multiple myeloma both in vitro and in vivo. It induces cell cycle arrest in the G2 phase and promotes apoptosis via the mitochondrial pathway [1].

LSD1 HDAC6-IN-1 is an orally active dual inhibitor targeting lysine specific demethylase 1 (LSD1) and histone deacetylase 6 (HDAC6), demonstrating promising anti-tumor activity, particularly valuable for multiple myeloma (MM) research [1].

Compound 12C, modified by altering cap groups, exhibits broad-spectrum enzyme inhibitory activity, as demonstrated in enzyme inhibition assays. Conversely, compounds 9m and 9q display a predilection towards HDAC6 inhibition, indicating subtype-selective inhibitory properties among the tested variants.

Tubacin is a highly potent and selective, reversible, cell-permeable HDAC6 inhibitor with an IC50 of 4 nM, approximately 350-fold selectivity over HDAC1.

CAY10603 (BML-281) is a potent and selective HDAC6 inhibitor.

HDAC-IN-6 is an HDAC inhibitor, targeting HDAC2, HDAC3, HDAC4, HDAC5, HDAC7, HDAC8, and HDAC9.

Belinostat (PXD101) is an inhibitor of hydroxamic acid-type histone deacetylase (HDAC, IC50 of 27 nM in HeLa cell extracts),and with antineoplastic activity.

Bufexamac (Bufexamic acid) is a COX inhibitor for IFN-α release with anti-inflammatory, analgesic, and antipyretic action.

HDAC-IN-57 is an orally active pan-inhibitor of histone deacetylase (HDAC), inhibiting HDAC1, HDAC2, HDAC6, and HDAC8 with IC50 values of 2.07 nM, 4.71 nM, 2.4 nM, and 107 nM, respectively. HDAC-IN-57 inhibits LSD1 with an IC50 value of 1.34 μΜ. HDAC-IN-57 has anti-tumor activity and can induce apoptosis.

Givinostat hydrochloride (ITF2357 hydrochloride) is an inhibitor of HDAC with IC50 of 198 and 157 nM for HDAC1 and HDAC3, respectively. Givinostat hydrochloride exhibits anti-inflammatory, anti-angiogenic, and antineoplastic activities.

MC2590 is a potent and selective histone deacetylase (HDAC) inhibitor that inhibits HDAC1-3, -6, -8, and -10 activities, induces cell cycle arrest, and promotes apoptosis.