hdac in 5

HDAC-IN-5 is a histone deacetylase (HDAC) inhibitor [inducing apoptosis, with potential antineoplastic (antitumor) and chemopreventive activities], inhibiting cell proliferation and regulating cell differentiation (IC50=0.0056 µM, 72 h) in murine erythroleukemia cells.

(2E)-N-(4-methoxyphenyl)-3-[3-(4-methylphenyl)-1-phenyl-1H-pyrazol-4-yl]prop-2-enamide is a compound used as a molecular structural unit.

PDE5/HDAC-IN-1 is a potent inhibitor of phosphodiesterase 5 (PDE5) and HDAC, with IC50 values of 46.3 nM and 14.5 nM, respectively.

HDAC6degrader-5 (Compound 6) exhibits inhibitory and degradative activity against HDAC6, with an IC50 of 4.95 nM and a DC50 of 0.96 nM. It suppresses the release of TNF-α, IL-1β, and IL-6, and prevents apoptosis in liver cells. Additionally, HDAC6degrader-5 demonstrates anti-inflammatory properties in a mouse model of APAP-induced liver injury.

PROTACHDAC6 degrader 5 (Compound 5a) is a highly selective PROTAC that targets HDAC6. It effectively degrades HDAC6 in cells with an IC50 of 43 nM. This compound reduces HDAC6 levels through a proteasome-dependent mechanism that relies on CRBN.

HDAC6ligand-5 is a binding ligand for HDAC6 and can be utilized in the synthesis of PROTACs, such as PROTACHDAC6 degrader5.

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]

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.

HDAC8-IN-5 (Compound 6a), with an inhibitory concentration (IC50) of 28 nM, is a potent HDAC8 inhibitor suitable for cancer research [1].

HDAC3-IN-5 (9c) is a selective inhibitor of HDAC3, exhibiting IC50 values of 4.2 nM for HDAC3, 1629 nM for HDAC2, and 298.2 nM for HDAC1. In vitro, it effectively induces apoptosis in MV4-11 cells and reduces the expression of anti-apoptotic proteins. The development of selective HDAC3 inhibitors like HDAC3-IN-5 (9c) could serve as potential lead compounds for reversing Venetoclax resistance.

HDAC-IN-51 is an HDAC inhibitor.

HDAC-IN-53 is an orally active, selective inhibitor of HDAC1-3, with 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 and murine tumor growth in immune-competent mice with MC38 colon cancer [1].

HDAC-IN-52, a pyridine-containing HDAC inhibitor, effectively inhibits HDAC1, HDAC2, HDAC3, and HDAC10 with IC50 values of 0.189, 0.227, 0.440, and 0.446 μM, respectively. HDAC-IN-52 can be used in cancer research.

HDAC-IN-50, a potent, orally active inhibitor targeting both FGFR (Fibroblast Growth Factor Receptor) and HDAC (Histone Deacetylase), exhibits IC50 values of 0.18, 1.2, 0.46, 1.4, 1.3, 1.6, 2.6, 13 nM for FGFR1, FGFR2, FGFR3, FGFR4, HDAC1, HDAC2, HDAC6, HDAC8, respectively. This dual inhibitor induces apoptosis and cell cycle arrest at the G0/G1 phase while decreasing the expression of phosphorylated FGFR1 (pFGFR1), phosphorylated ERK (pERK), and phosphorylated STAT3 (pSTAT3), thus demonstrating anti-tumor activity.

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.

HDAC-IN-55(8j) is a small-molecule inhibitor that enhances E-cadherin expression and suppresses cancer cell proliferation [1].

HDAC-IN-59 (compound 13a), a potent histone deacetylase (HDAC) inhibitor, enhances intracellular reactive oxygen species (ROS) production, induces DNA damage, arrests the cell cycle at the G2/M phase, and triggers the mitochondrial apoptotic pathway, leading to cell apoptosis [1].

HDAC-IN-58, a selective HDAC6 inhibitor, exhibits potent inhibitory activity with an IC50 of 2.06 nM, rendering it suitable for research into chronic neurodegenerative and psychiatric disorders [1].

HDAC-IN-56 ((S)-17b), an orally active inhibitor of class I histone deacetylase (HDAC), exhibits inhibitory constants (IC 50) of 56.0 ± 6.0 nM for HDAC1, 90.0 ± 5.9 nM for HDAC2, 422.2 ± 105.1 nM for HDAC3, and greater than 10,000 nM for HDAC4-11. This compound displays robust antitumor activity [1], marked by its ability to significantly elevate intracellular acetylhistone H3 and P21 levels, while also inducing G1 cell cycle arrest and apoptosis effectively.

CHDI-390576 is a CNS-permeable, selective and potent dibenzoyl isohydroxamic acid class IIa histone deacetylase (HDAC) inhibitor that inhibits class IIa HDAC 4, HDAC 5, HDAC 7, HDAC 9, and can be used in cancer research.

HDAC6-IN-49 (Compound 3) is an inhibitor of HDAC, with IC50 values of 0.012 and 0.735 µM against HDAC6 and HDAC1, respectively. Additionally, it inhibits MAO-B, cholinesterase (ChE), histamine receptor (H3R), and serotonin 6 receptor (5-HT6R). HDAC6-IN-49 exhibits neuroprotective effects in SH-SY5Y cells and enhances cognitive functions and motor abilities in fruit fly models of Parkinson's disease and C. elegans models of Alzheimer's disease.

HDAC-IN-80 (compound 5) is a selective inhibitor of class I HDAC.

HDAC-IN-83 (compound 9D) is an inhibitor of histone deacetylase (HDAC), demonstrating an IC50 of 0.01 μM for HDAC1 and 0.44 μM for HDAC6. It exhibits anticancer and antiproliferative activities and promotes caspase-3/7 activation. The compound inhibits Cal27, HepG2, and MRC-5 cells with IC50 values of 0.693 μM, 0.427 μM, and 3.19 μM, respectively.

Givinostat (ITF-2357) is an HDAC inhibitor with IC50 values of 198 nM for HDAC1 and 157 nM for HDAC3.