HDAC6 Inhibitor

Puzerinostat (Purinostat) is a highly selective class I/IIb histone deacetylase (HDAC) inhibitor, with IC₅₀ values of 0.81 nM, 1.4 nM, 1.7 nM, 3.8 nM, 11.5 nM, and 1.1 nM against HDAC1, HDAC2, HDAC3, HDAC8, HDAC6, and HDAC10, respectively. Puzerinostat enhances glutamine metabolism by upregulating GLS1. Puzerinostat induces cell Apoptosis and downregulates the expression of BCR-ABL and c-MYC. Puzerinostat delays the progression of Ph⁺ B-cell acute lymphoblastic leukemia and prolongs the survival of relevant mouse models. Puzerinostat regulates the immune microenvironment. Puzerinostat can be used in research related to chronic myeloid leukemia, Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia, relapsed/refractory multiple myeloma, relapsed/refractory lymphoma, diffuse large B-cell lymphoma, and double-expression lymphoma.

AES-135, a hydroxamic acid-based pan-HDAC inhibitor, prolongs survival in an orthotopic mouse model of pancreatic cancer. AES-135 inhibits HDAC3, HDAC6, HDAC8, and HDAC11 with IC₅₀s ranging from 190-1100 nM.

HPOB is a highly potent and selective inhibitor of HDAC6 with an IC₅₀ of 56 nM. HPOB displays >30 fold less potent against other HDACs. HPOB enhances the effectiveness of DNA-damaging anticancer agents in transformed cells but not normal cells. HPOB does not block the ubiquitin-binding activity of HDAC6.

SIRT6-IN-3 (compound 8a) is a selective inhibitor of SIRT6 (IC₅₀=7.49 μM). SIRT6-IN-3 inhibits pancreatic ductal adenocarcinoma (PDAC) cells proliferation and induces apoptosis. SIRT6-IN-3 increases the sensitivity of cancer cells to gemcitabine (HY-17026) via blocking the DNA damage repair pathway. SIRT6-IN-3 is used in pancreatic cancer research.

HDAC6 degrader-5 (Compound 6) exhibits inhibitory and degradation activity against HDAC6, with an IC₅₀ of 4.95 nM and a DC₅₀ of 0.96 nM. HDAC6 degrader-5 inhibits the release of TNF-α, IL-1β and IL-6, blocks the hepatocyte apoptosis. HDAC6 degrader-5 exhibits anti-inflammatory activity in mouse APAP (HY-66005)-induced liver injury models.

HDAC6-IN-33 (compound 6) is a selective and irreversible HDAC6 inhibitor with an IC₅₀ of 193 nM. HDAC6-IN-33 shows no activity against HDAC1-4. HDAC6-IN-33 is a tight-binding HDAC6 inhibitor capable of inhibiting HDAC6 via a two-step slow-binding mechanism.

BRD73954 is a potent HDAC inhibitor and selectively inhibiting both HDAC6 and HDAC8 with IC₅₀ values of 0.0036, 0.12, 9, 12, 23 µM for HDAC6, HDAC8, HDAC2, HDAC1 and HDAC3, respectively. BRD73954 decreases the levels of HDAC6, associated with upregulation of Ac-Tubulin.

MC1742 is a potent HDAC inhibitor, with IC₅₀s of 0.1 μM, 0.11 μM, 0.02 μM, 0.007 μM, 0.61 μM, 0.04 μM and 0.1 μM for HDAC1, HDAC2, HDAC3, HDAC6, HDAC8, HDAC10 and HDAC11, respectively. MC1742 can increase acetyl-H3 and acetyl-tubulin levels and inhibits cancer stem cells growth. MC1742 can induce growth arrest, apoptosis, and differentiation in sarcoma CSC.

SelSA is a selective, orally active inhibitor for histone deacetylase 6 (HDAC6) with IC₅₀ of 56.9 nM. SelSA inhibits the phosphorylation of ERK1/2. SelSA inhibits the proliferation of breast cancer cells and hepatocellular carcinoma cells with IC₅₀ of 0.58-2.6 μM, inhibits cell migration and invasion of Huh7, and induces apoptosis. SelSA exhibits antitumor activity in mouse model.

ITF 3756 is a selective, orally active HDAC6 inhibitor. ITF 3756 antagonizes TNF-α-induced activation of the NF-κB pathway. ITF 3756 reduces PD-L1 expression on human monocytes and CD8⁺ T cells, and exhibits antitumor activity. ITF 3756 can be used in colon cancer-related research.

JAK/HDAC-IN-1 is a potent JAK2/HDAC dual inhibitor, exhibits antiproliferative and proapoptotic activities in several hematological cell lines. JAK/HDAC-IN-1 shows IC₅₀s of 4 and 2 nM for JAK2 and HDAC, respectively.

FNDR-20123 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 exerts anti-malarial activity against Plasmodium falciparum asexual stage (IC₅₀=41 nM) and sexual blood stage (IC₅₀=190 nM for male gametocytes). FNDR-20123 inhibits HDAC1, HDAC2, HDAC3, HDAC6, and HDAC8 (IC₅₀=25/29/2/11/282 nM, respectively.) and inhibits Class III HDAC isoforms at nanomolar concentrations.

HDAC10-IN-3 (Compound 2a) is a potent HDAC10 inhibitor with an IC₅₀s of 0.41, 37, 350 and 4500 nM against HDAC10, HDAC6, HDAC8 and HDAC1. HDAC10-IN-3 exhibits moderate cytotoxicity in KB and SK-OV-3 cells, but does not show significant cytotoxicity against most cancer cell lines. HDAC10-IN-3 can be used for the study of cancers.

HDAC8-IN-8 (15a) is an HDAC8 inhibitor, with IC₅₀ values of 23.9 μM and 268.2 μM for hHDAC8 and smHDAC8 respectively. And for hHDAC1 and hHDAC6, the IC₅₀ values are 12.1 μM and 2.9 μM respectively. HDAC8-IN-8 can be used in schistosomiasis-related research.

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.

1-Naphthohydroxamic acid (Compound 2) is a potent and selective HDAC8 inhibitor with an IC₅₀ of 14 μM. 1-Naphthohydroxamic acid is more selectively for HDAC8 than class I HDAC1 and class II HDAC6 (IC₅₀ >100 μM). 1-Naphthohydroxamic acid does not increase global histone H4 acetylation and also does not reduce total intracellular HDAC activity.1-Naphthohydroxamic acid can induce tubulin acetylation.

HDAC6-IN-46 (compound 12) is a selective histone deacetylase 6 (HDAC6) inhibitor with an IC₅₀ value of 6.2 nM. HDAC6-IN-46 can be used in Alzheimer's disease research.