HDAC4 Inhibitor

Givinostat (ITF-2357) hydrochloride is a HDAC inhibitor with an IC₅₀ of 198 and 157 nM for HDAC1 and HDAC3, respectively. Givinostat hydrochloride can penetrate the blood-brain barrier (BBB)..

Bavarostat (EKZ-001) is a blood-brain barrier-permeable, potent HDAC6 inhibitor and PET radiotracer, with an IC₅₀ as low as 17 nM against human HDAC6. Bavarostat can be labeled with ¹⁸F and used as a probe to map HDAC6 distribution and measure target occupancy in the brains of non-human primates. Bavarostat also selectively modulates tubulin acetylation, but not histone acetylation. Bavarostat is applicable for research on Alzheimer's disease, other neurodegenerative disorders, and cancers.

NT160 is a highly potent class-IIa HDAC inhibitor with an IC₅₀ value of 0.046 μM. NT160 can be used for the research of central nervous system diseases.

PTACH (NCH-51) is a potent HDAC inhibitor with IC₅₀s of 48 nM, 32 nM, and 41 nM for HDAC1, HDAC4, and HDAC6, respectively. PTACH exerts potent growth inhibition against various cancer cells (EC₅₀s of 1.1-9.1 μM) .

HDAC4-IN-1 (compound 1a) is a class IIa HDACI inhibitor (IC₅₀=0.077 μM). HDAC4-IN-1 can enhance Caspase-induced Apoptosis. HDAC4-IN-1 has anticancer activity. HDAC4-IN-1 can be used in the research of drug combination against cancer.

HDAC-IN-40 is a potent alkoxyamide-based HDAC inhibitor with K_i values of 60 nM and 30 nM for HDAC2 and HDAC6, respectively. HDAC-IN-40 had antitumor effects.

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.

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.

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.

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-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.

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.

HDAC6-IN-17 (compound 5b) is a potent HDAC6 inhibitor with IC₅₀ values of 150 nM, 1400 nM, and 2300 nM for HDAC6, HDAC8, and HDAC4, respectively. HDAC6-IN-17 has cytotoxic activity on human cancer cell lines. HDAC6-IN-17 can be used in research of cancer.

(S)-Trichostatin A ((S)-TSA) is a HDAC6-selective inhibitor with IC₅₀s of 9.88 nM and 11.1 nM for Zebrafish HDAC6 and Human HDAC6, respectively. (S)-Trichostatin A weakly inhibits other human HDACs.

HDAC8-IN-6 (compound 3) is a potent HDAC8 inhibitor with an IC₅₀ of 5.1 μM. HDAC8-IN-6 shows cytotoxicity.

HDAC-IN-36 (compound 23 g) is an orally active and potent HDAC (histone deacetylase) inhibitor, with an IC₅₀ of 11.68 nM (HDAC6). HDAC-IN-36 promotes apoptosis, autophagy and suppresses migration. HDAC-IN-36 shows anti-tumor and anti-metastatic activity, and can be used for breast cancer research.

TNI-97 is a selective and orally active HDAC6 inhibitor, with an IC₅₀ of 0.2 nM. TNI-97 potently inhibited TNBC cell MDA-MB-453 growth and clonogenicity. TNI-97 induces PANoptosis including apoptosis, necroptosis and pyroptosis in MDA-MB-453 cells. TNI-97 shows antitumor activity in the mice carrying the MDA-MB-453 xenograft or carrying murine-derived TNBC cell allografts. TNI-97 can be used for the study of triple-negative breast cancer.

HDAC8-IN-3 (compound P19) is a potent HDAC8 inhibitor with IC₅₀ value of 9.3 μM and produces thermal stabilization. HDAC8-IN-3 has cytotoxicity and induces apoptosis in leukemic cell lines.

PI3K/HDAC-IN-2 is a potent dual PI3K/HDAC inhibitor with IC₅₀s of 226 nM, 279 nM, 467 nM, 29 nM for PI3Kα, PI3Kβ, PI3Kγ, PI3Kδ, respectively, and IC₅₀s of 1.3 nM, 3.4 nM, 972 nM, 17 nM, 12 nM for HDAC1, HDAC2, HDC4, HDAC6, HDAC8, respectively. PI3K/HDAC-IN-2 exhibits PI3Kδ and class I and IIb HDAC selectivity. PI3K/HDAC-IN-2 has remarkable anticancer effects.

HDACs/EZH2-IN-1 (Compound 22a) is a HDACs/EZH2 inhibitor (EZH2 Y641N inhibition rate at 50 nM: 98%), with selective inhibition against HDAC1 and HDAC6 (IC₅₀: 0.23 μM and 0.07 μM, respectively). HDACs/EZH2-IN-1 exerts a antiproliferative effect on diffuse large B-cell lymphoma cells harboring an EZH2 mutation and on various acute myeloid leukemia cells. HDACs/EZH2-IN-1 has the ability to induce cell differentiation and Apoptosis.