HDAC2 Inhibitor

BG45 is a potent HDAC3 inhibitor with IC₅₀ values of 0.289, 2, 2.2 and ﹥20 μM for HDAC3, HDAC1, HDAC2 and HDAC6, respectively. BG45 selectively targets multiple myeloma (MM) cells and induces caspase-dependent apoptosis.

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.

BRD6688 is a selective HDAC2 inhibitor. BRD6688 increases H4K12 and H3K9 histone acetylation in primary mouse neuronal cells. BRD6688 crosses the blood brain barrier and rescues the memory defects associated with p25 induced neurodegeneration in contextual fear conditioning in a CK-p25 mouse model.

Imofinostat (ABT-301; MPT0E028) is an orally active and selective HDAC inhibitor with IC₅₀s of 53.0 nM, 106.2 nM, 29.5 nM for HDAC1, HDAC2 and HDAC6, respectively. Imofinostat has a weak inhibitory effect on HDAC8 (IC₅₀ of 2.5 ​​μM), but no inhibitory effect on HDAC4 (IC₅₀>10 μM). Imofinostat reduces the viability of B-cell lymphomas by inducing apoptosis and possesses potent direct Akt targeting ability and reduces Akt phosphorylation in B-cell lymphoma. Imofinostat has a broad-spectrum antitumor activity, including colorectal cancer, B-cell lymphoma, non-small cell lung carcinoma (NSCLC), and pancreatic cancer, while also showing therapeutic potential in non-tumor diseases like emphysema and pulmonary fibrosis.

Crebinostat is a potent histone deacetylase (HDAC) inhibitor with IC₅₀ values of 0.7 nM, 1.0 nM, 2.0 nM and 9.3 nM for HDAC1, HDAC2, HDAC3 and HDAC6, respectively. Crebinostat potently induces acetylation of both histone H3 and histone H4 as well as enhances the expression of the cAMP response element-binding protein (CREB) target gene Egr1. Crebinostat increases the density of synapsin-1 punctae along dendrites in cultured neurons. Crebinostat can modulate chromatin-mediated neuroplasticity and exhibits enhanced memory in mice.

WT-161 is a potent and selective HDAC6 inhibitor with an IC₅₀ of 0.40 nM. WT-161 also inhibits metallo-β-lactamase domain-containing protein 2 (MBLAC2).

BRD2492 (compound 6d) is a potent, selective HDAC1 and HDAC2 inhibitor with IC₅₀s of 13.2 nM and 77.2 nM, respecrtively. BRD2492 exhibits >100-fold selectivity for HDAC1/2 over selectivity over HDAC3 and HDAC6. BRD2492 inhibits breast cancer cell lines growth with IC₅₀s of 1.01 μM and 11.13 μM for T-47D and MCF-7 cells, respectively.

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.

NKL 22 is a potent and selective inhibitor of histone deacetylases (HDAC), with IC₅₀ values of 199 and 69 nM for HDAC1 and HDAC3, respectively. NKL 22 can reverse abnormal expression of HD‑related genes and restore the levels of key genes including Ppp1r1b in Huntington's disease transgenic mice. NKL 22 can be used for the researches of Huntington's disease and cancer.

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.

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.

Domatinostat tosylate (4SC-202) is a selective class I HDAC inhibitor with IC₅₀ of 1.20 μM, 1.12 μM, and 0.57 μM for HDAC1, HDAC2, and HDAC3, respectively. It also displays inhibitory activity against Lysine specific demethylase 1 (LSD1).

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.

KPZ560 is a potent inhibitor of HDAC1 and HDAC2, with IC₅₀s of 12 nM and 68 nM, respectively. KPZ560 can increase in the spine density of granule neuron dendrites of mice and inhibitor cell growth of breast cancer cell line MCF.

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.

HDAC-IN-27 dihydrochloride (Compound 11h) is a potent, orally active class I HDAC-selective inhibitor with IC₅₀ values ranging from 0.43 to 3.01 nM against HDAC1-3. HDAC-IN-27 dihydrochloride exhibits both in vivo and in vitro antitumor activity. HDAC-IN-27 dihydrochloride demonstrates significant anti-proliferative activity against acute myeloid leukemia (AML) cell lines by inducing apoptosis and histone acetylation (AcHH3 and AcHH4). HDAC-IN-27 dihydrochloride can be used for research in acute myeloid leukemia (AML).

BG48 is a potent HDAC inhibitor. BG48 inhibits the enzymatic activity of HDAC1 and HDAC2.

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.

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.