hdac in 6

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

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

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

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

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

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

HDAC6-IN-17 (compound 5b) is a potent inhibitor of HDAC6, exhibiting IC50 values of 150 nM for HDAC6, 1400 nM for HDAC8, and 2300 nM for HDAC4. It demonstrates cytotoxic activity against human cancer cell lines and is 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). HDAC6-IN-5 inhibits Aβ 1-42 self-aggregation and AChE, with IC 50s of 3.0 and 0.72 μM. HDAC6-IN-5 can enhance neurite outgrowth without significant neurotoxicity.

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-IN-6 (compound 6a) is a potent inhibitor of HDAC6 that can penetrate BBB with an IC50 value of 0.025 μM. HDAC6-IN-6 has potent inhibitory activity against AChE and Aβ 1-42 self-aggregation with IC50 values of 0.72 and 3.0 μM. HDAC6-IN-6 can enhance the outgrowth of neurite without significant neurotoxicity [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 demonstrates inhibitory activity against 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 displays anti-inflammatory properties [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].

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

PI3Kα/HDAC6-IN-1 (compound 21j) is a dual inhibitor of PI3Kα and HDAC6, exhibiting IC50 values of 2.9 nM and 26 nM, respectively. It effectively hinders AKT(Ser473) phosphorylation and promotes the build-up of acetylated α-tubulin, while not influencing acetylated histones H3 and H4. The compound demonstrates potent anti-cancer efficacy by inhibiting the L-363 cell line with an IC50 of 0.17 μM [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].

HDAC6-IN-9 (compound 12c) is a potent and selective inhibitor of HDAC6 with anti-proliferative activities. The IC 50 values of HDAC6-IN-9 for HDAC6, HDAC1,HDAC3, HDAC8, and HDAC10 is 4.2, 11.8, 15.2, 139.6, and 21.3 nM, respectively [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.

HDAC1/6-IN-1 is a potent multi-target inhibitor of GLP (IC50: 1.3 nM), HDAC6 (IC50: 13 nM) and HDAC1 (IC50: 89 nM). HDAC1/6-IN-1 inhibits the methylation and deacetylation of H3K9 at the protein level. HDAC1/6-IN-1 can block the cell cycle of cancer cells in G0/G1 phase, induce apoptosis and prevent cancer cell migration and invasion.

BChE/HDAC6-IN-1 is a dual BChE/HDAC6 inhibitor that exhibits 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 that targets 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. In addition, it inhibits BRPF1 with a Kd value of 175.2 nM. This compound is utilized in cancer research [1].

HDAC6-IN-11 (Compound 9) has anti-proliferative activities against cancer cells. HDAC6-IN-11 is a selective inhibitor of HDAC6 with the IC50 value of 20.7 nM. The selectivity of HDAC6-IN-11 is more than 300-fold over HDAC other isoforms [1].

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-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, potent and non-significantly toxic HDAC6 inhibitor (IC50: 23 nM). HDAC6-IN-4 induces apoptosis and exhibits potent anti-tumor effects.

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/HSP90-IN-2 (compound 6e) is a dual inhibitor targeting HDAC6 and Hsp90, exhibiting IC50 values of 105.7 nM and 61 nM, respectively. It is primarily utilized in cancer research [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 compound that functions as a dual inhibitor, targeting lysine specific demethylase 1 (LSD1) and histone deacetylase 6 (HDAC6). This compound demonstrates promising anti-tumor activity and is particularly valuable for research focused on multiple myeloma (MM) [1].

HDAC3/6-IN-2 (compound 15) is a dual inhibitor targeting HDAC6 and HDAC3, exhibiting potent activity with IC50 values of 0.368 μM for HDAC6 and 0.635 μM for HDAC3. This compound demonstrates antitumor effects by inducing apoptosis in cancer cells and reducing HDAC6 and HDAC3 levels. This action is linked to the increased acetylation of H3 and α-tubulin [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.

HDAC-IN-64 (Compound 13), an HDAC inhibitor, demonstrates potent inhibition of HDAC4/5/6/7/9 with IC50 values of 24, 45, 85, 31, and 37 nM, respectively. It exhibits anti-proliferative and anti-migration effects on prostate cancer (PCA) cells, specifically inhibiting the growth of LNCaP and RWPE-1 cells with GI50 values of 0.32 and 1.1 μM, respectively [1].

Givinostat (ITF-2357) is a HDAC inhibitor with an IC50 of 198 and 157 nM for HDAC1 and HDAC3, respectively. Givinostat (ITF2357) suppresses total LPS-induced IL-1β production robustly compared with the reduction by ITF3056. At 25, 50, and 100 nM, Givinostat reduced IL-1β secretion more than 70%. Givinostat (ITF-2357) suppresses the production of IL-6 in PBMCs stimulated with TLR agonists as well as the combination of IL-12 plus IL-18. IL-6 secretion decreases to 50% at 50 nM Givinostat, but at 100 and 200 nM, there is no reduction[1]. As shown by the CCK-8 assay, Givinostat (ITF-2357) inhibits JS-1 cell proliferation in a concentration-dependent manner. Treatment with Givinostat ≥500 nM is associated with significant inhibition of JS-1 cell proliferation (P<0.01). Also, the cell inhibition rate significantly differs between the group cotreated with Givinostat ≥250 nM plus LPS and the group without LPS treatment (same Givinostat concentration) (P<0.05)[2]. Givinostat (ITF2357) at 10 mg/kg is used as a positive control and, as expected, reduced serum TNFα by 60%. Strikingly, pretreatment of ITF3056 starting at 0.1 mg/kg significantly reduces the circulating TNFα by nearly 90%. To achieve a significant increase in serum IL-1β production, a higher dose of LPS is injected (10 mg/kg), and blood is collected after 4 h. Similarly, when pretreated with lower doses of Givinostat (ITF-2357) (1 or 5 mg/kg), there is a 22% reduction for 1 mg/kg and 40% for 5 mg/kg[1]. [1]. Li S, et al. Specific inhibition of histone deacetylase 8 reduces gene expression and production of proinflammatory cytokines in vitro and in vivo. J Biol Chem. 2015 Jan 23;290(4):2368-78. [2]. Wang YG, et al. Givinostat inhibition of hepatic stellate cell proliferation and protein acetylation. World J Gastroenterol. 2015 Jul 21;21(27):8326-39. [3]. Leoni F, et al. The histone deacetylase inhibitor ITF2357 reduces production of pro-inflammatory cytokines in vitro and systemic inflammation in vivo. Mol Med. 2005 Jan-Dec;11(1-12):1-15.

KH16 is a potent HDAC inhibitor that specifically targets class I HDACs (HDAC1, HDAC2 and HDAC3) with IC50 values between 6 and 34 nM. KH16 is able to stimulate apoptosis and can inhibit gene expression patterns in a wide range of tumor cells.

Butyricacid-d7 is a deuterated compound of Butyricacid. Butyricacid has a CAS number of 107-92-6. Butyric acid is a fatty acid isolated from many dairy products that exhibits anticancer activity. Butyric acid inhibits histone deacetylases (HDACs) and induces apoptosis and G1 phase cell cycle arrest in glioma cells. Additionally, butyric acid stimulates epithelial cell proliferation at low doses and inhibits proliferation at high doses.

HDAC4 CHDI Degrader 11 is a potent, selective degrader of HDAC4 (PROTAC) with DC_50 values of 4 nM and 6 nM in Jurkat E6-1 and Jurkat cells, respectively. This compound integrates the class IIa HDAC inhibitor trifluoromethyloxadiazole with a ligand for the Von Hippel-Lindau (VHL) protein through a linker. Demonstrating significant efficacy, HDAC4 CHDI Degrader 11 achieves a DC_50 value of 1 nM in a mouse cell model of Huntington's disease. For enhanced degradation in neuroblastoma cell lines, it can be administered alongside the P-glycoprotein inhibitor, Elacridar.

PIM-1/HDAC-IN-1 (compound 4d) is a potent inhibitor of PIM-1, with an IC 50 of 343.87 nM. It also exhibits strong inhibitory activity and selectivity against HDAC 1 and HDAC 6, with IC 50 values of 63.65 and 62.39 nM, respectively. Furthermore, PIM-1/HDAC-IN-1 demonstrates apoptosis-inducing potential in MCF-7 cell lines, specifically inducing pre-G1 apoptosis and causing cell cycle arrest at the G2/M phase [1].

HDAC-IN-53 is an orally active, selective inhibitor of HDAC1-3, demonstrating IC50 values of 47 nM, 125 nM, and 450 nM, respectively. It exhibits no inhibitory effects on class II HDACs (HDAC4, 5, 6, 7, 9; IC50 >10 μM). The compound induces caspase-dependent apoptosis and significantly hampers the growth of human tumor xenografts in nude mice, as well as murine tumor growth in immune-competent mice with MC38 colon cancer [1].

Fluoxetine succinate ester is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is used for the treatment of major depressive disorder, obsessive–compulsive disorder, bulimia nervosa, panic disorder, and premenstrual dysphoric disorder.

CDK/HDAC-IN-1 exhibits potent inhibitory activity towards CDK2/4/6 and HDAC6, with IC50 values of 60.9 ± 2.9 nM, 276 ± 22.3 nM, 27.2 ± 4.2 nM, and 128.6 ± 0.4 nM, respectively.

HDAC-IN-38 is a potent inhibitor of HDAC. HDAC-IN-38 has similar micromolar inhibitory effects on HDAC1, 2, 3, 5, 6 and 8, and also increases histone acetylation levels (H3K14 or H4K5). HDAC-IN-38 increases cerebral blood flow (CBF), reduces cognitive impairment and improves hippocampal atrophy.

BG45 is an HDAC I type inhibitor with IC50 of 289 nM, 2.0 μM, 2.2 μM and >20 μM for HDAC3 1 2 6 in cell-free assays, respectively.

JAK/HDAC-IN-2, a potent 2-amino-4-phenylaminopyrimidine dual-target inhibitor, effectively suppresses JAK1/2 and HDAC3/6 at nanomolar concentrations. This compound exhibits proapoptotic properties, inhibits histone deacetylation, and impedes STAT3 phosphorylation, demonstrating notable antiproliferative activity against various hematological malignancies and solid tumors [1].

HDAC-IN-43 is a potent HDAC 1/3/6 inhibitor with IC50 values of 82 nM for HDAC 1, 45 nM for HDAC 3, and 24 nM for HDAC 6. HDAC-IN-43 is a weak PI3K/mTOR inhibitor with IC50 values of 3.6 μM for PI3K and 3.7 μM for mTOR. HDAC-IN-43 has a broad-spectrum anti-proliferative effect.