HDAC6 Inhibitor

CHDI-00484077 (Compound 12) is a CNS-penetrant class IIa HDAC inhibitor, with IC₅₀s of 0.01 μM (HDAC4), 0.02 μM(HDAC5), 0.02 μM (HDAC7), 0.03 μM (HDAC9) respectively. CHDI-00484077 can be used for research of huntington’s disease.

AES-350 is a potent and orally active HDAC6 inhibitor with an IC₅₀ and a K_i of 0.0244 μM and 0.035 μM, respectively. AES-350 is also against HDAC3, HDAC8 in an enzymatic activity assay with IC₅₀ values of 0.187 μM and 0.245 μM, respectively. AES-350 triggers apoptosis in AML cells through HDAC inhibition and can be used for acute myeloid leukemia (AML) research.

BRD9757 is a potent, capless and selective HDAC6 inhibitor with an IC₅₀ of 30 nM. BRD9757 shows excellent selectivity toward HDAC6 versus the class I (>20-fold) and class II (>400-fold) HDACs.

PROTAC HDAC6 degrader 7 is an orally active, highly efficient, and selective PROTAC degrader targeting histone deacetylase 6 (HDAC6) (IC₅₀ = 118 nM). PROTAC HDAC6 degrader 7 can eliminate both the catalytic and zinc-finger ubiquitin-binding domain. PROTAC HDAC6 degrader 7 inhibits NLRP3 inflammasome assembly and activation, as well as blocks NF-κB signaling, thereby reducing the transcription and release of key inflammatory factors. PROTAC HDAC6 degrader 7 can reduce the mRNA levels of NLRP3, pro-IL-1β, TNF-α, and IL-6. PROTAC HDAC6 degrader 7 can be used for the study of inflammatory bowel disease (IBD).

HDAC-IN-53 is an orally active, and selective HDAC1-3 inhibitor with IC₅₀ values of 47 nM, 125 nM, and 450 nM, respectively. HDAC-IN-53 does not inhibit class II HDACs (HDAC4, 5, 6, 7, 9; IC₅₀>10 μM). HDAC-IN-53 induces caspase-dependent apoptosis. HDAC-IN-53 significantly inhibits the growth of human tumor xenografts in nude mice and murine tumor growth in immune-competent mice bearing MC38 colon cancer.

LSD1/HDAC-IN-2 (Compound 20c) is the inhibitor for LSD and HDAC, that inhibits LSD1, HDAC1, HDAC2, HDAC3, HDAC6, and HDAC8, with IC₅₀s of 39.0, 1.4, 1.0, 1.3, 2.9 and 16.0 nM, respectively. LSD1/HDAC-IN-2 inhibits the proliferation of cancer cells, especially the colorectal cancer cells. LSD1/HDAC-IN-2 arrests the cell cycle at G2/M phase, inhibits cell migration, and induces apoptosis in HCT-116 and HT-29 cells. LSD1/HDAC-IN-2 exhibits antitumor efficacy in mouse model without significant toxicity.

QTX125 is a potent and highly selective HDAC6 inhibitor. QTX125 exhibits excellent selectivity over other HDACs. QTX125 has antitumor effects.

QTX125 TFA is a potent and highly selective HDAC6 inhibitor. QTX125 TFA exhibits excellent selectivity over other HDACs. QTX125 has antitumor effects.

CRA-026440 hydrochloride is a potent, broad-spectrum HDAC (HDAC) inhibitor. The K_i values against recombinant HDAC isoenzymes HDAC1, HDAC2, HDAC3, HDAC6, HDAC8, and HDAC10 are 4 nM, 14 nM, 11 nM, 15 nM, 7 nM, and 20 nM respectively. CRA-026440 hydrochloride shows antitumor and antiangiogenic activities. CRA-026440 (hydrochloride) is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.

XSJ-10 is a HDAC inhibitor containing a RAS/RAF protein interfering unit, with IC_50s of 0.05 and 0.04 μM in PANC-1 cells and HT-29 cells. XSJ-10 can effectively induce the apoptosis of cancer cells and suppress the tumor by strongly inhibiting the RAS-RAF-MEK-ERK signaling pathway and the acetylation level of HDAC3.

HDAC6-IN-13 (Compound 35m) is a potent, highly selective, orally active HDAC6 inhibitor with an IC₅₀ of 0.019 μM. HDAC6-IN-13 also inhibits HDAC1, HDAC2 and HDAC3 with IC₅₀s of 1.53, 2.06 and 1.03 μM, respectively. HDAC6-IN-13 shows significant BBB permeability and anti-inflammatory activity.

MPT0G211 mesylate is a potent, orally active and selective HDAC6 inhibitor (IC₅₀=0.291 nM). MPT0G211 mesylate displays >1000-fold selective for HDAC6 over other HDAC isoforms. MPT0G211 mesylate can penetrate the blood-brain barrier. MPT0G211 mesylate ameliorates tau phosphorylation and cognitive deficits in an Alzheimer’s disease model. MPT0G211 mesylate has anti-metastatic and neuroprotective effects. Anticancer activities.

HDAC6-IN-5 (compound 11b) is a potent and BBB-penetrated HDAC6 inhibitor, with an IC₅₀ of 0.025 μM. HDAC6-IN-5 exhibits strong inhibitory activity against Aβ_1-42 self-aggregation and AChE, with IC₅₀ values of 3.0 and 0.72 μM. HDAC6-IN-5 can enhance neurite outgrowth without significant neurotoxicity.

SHP2/HDAC-IN-1 is a dual allosteric SHP2/HDAC inhibitor with IC₅₀ values of 20.4 nM (SHP2) and 25.3 nM (HDAC1) respectively. SHP2/HDAC-IN-1 triggers efficient antitumor immunity by activating T cells, enhancing the antigen presentation function and promoting cytokine secretion. SHP2/HDAC-IN-1 can be used in the research of cancer immunoresearch.

PI3K/HDAC-IN-1 is a potent dual inhibitor of PI3K/HDAC, potently inhibits PI3Kδ and HDAC1 with IC₅₀s of 8.1 nM and 1.4 nM, respectively.

LSD1/HDAC6-IN-1 is an orally active dual inhibitor of lysine specific demethylase 1(LSD1)/Histone deacetylase 6 (HDAC6), with anti-tumor activity. LSD1/HDAC6-IN-1 can be used for the research of multiple myeloma (MM).

FNDR-20123 free base is a safe, first-in-class, and orally active anti-malarial HDAC inhibitor with IC₅₀s of 31 nM and 3 nM for Plasmodium and human HDAC, respectively. FNDR-20123 free base exerts anti-malarial activity against Plasmodium falciparum asexual stage (IC₅₀=41 nM) and sexual blood stage (IC₅₀=190 nM for male gametocytes). FNDR-20123 free base inhibits HDAC1, HDAC2, HDAC3, HDAC6, and HDAC8 (IC₅₀=25, 29, 2, 11, and 282 nM, respectively) and inhibits Class III HDAC isoforms at nanomolar concentrations.

ROCK/HDAC-IN-2 (Compound C-9) is a ROCK/HDAC inhibitor, with IC₅₀ values of 0.185 µM, 0.8 µM, and 0.7 µM for HDAC6, ROCK1, and ROCK2, respectively. ROCK/HDAC-IN-2 can induce apoptosis and changes in mitochondrial membrane potential in cancer cells, demonstrating significant antitumor activity. ROCK/HDAC-IN-2 can be used in the research of pancreatic ductal adenocarcinoma (PDAC) and triple-negative breast cancer (TNBC).

HDAC6-IN-6 (compound 6a) is a potent and BBB-penetrated HDAC6 inhibitor, with an IC₅₀ of 0.025 μM. HDAC6-IN-6 exhibits strong inhibitory activity against Aβ_1-42 self-aggregation and AChE, with IC₅₀ values of 3.0 and 0.72 μM. HDAC6-IN-6 can enhance neurite outgrowth without significant neurotoxicity.

Hsp110/HDAC6-IN-1 is an orally active Hsp110/HDAC6 dual inhibitor. Hsp110/HDAC6-IN-1 disrupts Hsp110-STAT3 protein-protein interaction, suppresses HDAC6 enzymatic activity, and suppresses STAT3 signaling pathway. Hsp110/HDAC6-IN-1 inhibits abnormal proliferation and migration of human pulmonary arterial endothelial cells, and suppresses pulmonary vascular remodeling in rats. Hsp110/HDAC6-IN-1 can be used for the research of pulmonary arterial hypertension.