HDAC2 Inhibitor

Nanatinostat (CHR-3996) TFA is a potent, class I selective and orally active HDAC inhibitor with IC₅₀s of 3 nM, 4 nM, and 7 nM for HDAC1, HDAC2, and HDAC3, respectively. Nanatinostat TFA has low activity against HDAC5 (IC₅₀ of 200 nM) and HDAC6 (IC₅₀ of 2100 nM). Nanatinostat TFA induces apoptosis in myeloma cells. Nanatinostat TFA has potent anticancer effects, such as myeloma, advanced solid tumours and colorectal cancer.

CM-414 is a brain-penetrant phosphodiesterase 5 (PDE5) and HDAC inhibitor with IC50s of 60 nM, 91 nM, 310 nM, 322 nM and 490 nM for PDE5, HDAC6, HDAC1, HDAC3 and HDAC2, respectively. CM-414 diminishes brain Aβ and tau phosphorylation (pTau) level in Tg2576 mice. CM-414 can be used for the study of Alzheimer's disease (AD).

MC2625 is a potent pyridine-containing histone deacetylase (HDAC) inhibitor. MC2625 show selective HDAC3 and HDAC6 inhibition with IC₅₀s of 80 nM and 11 nM. MC2625 increases acetyl-H3 and acetyl-tubulin levels and inhibits cancer stem cells (CSCs) growth by apoptosis induction.

IOR-160 is a dual inhibitor of casein kinase 2 (CK2) and HDACs. IOR-160 exhibits high selectivity for CK2 (IC₅₀ = 1.7 nM) and broad inhibitory activity against HDAC (HDAC 1, 2, 3, and 6 with IC₅₀s of 3.3 nM, 24.0 nM, 3.9 nM, and 13.0 nM, respectively, with low activity for HDAC8). IOR-160 modulates key cellular signaling pathways by inhibiting AKT phosphorylation and increasing acetylated α-tubulin. IOR-160 inhibits tumor growth and reduces tumor burden through dual CK2/HDAC inhibition. IOR-160 is indicated for use in triple-negative breast cancer research.

AC-340 is a potent hybrid VDR agonist/HDAC inhibitor. AC-340 superinduces VDR target genes (e.g., CYP24A1) and inhibits HDAC6 (IC₅₀ = 0.37 μM) with ~10-fold selectivity over HDAC2. AC-340 induces VDR hyperagonism by causing widespread protein hyperacetylation (e.g., tubulin and H3K9/K27), which leads to elevated H3K27 acetylation on VDR target genes. AC-340 can be used for melanoma cancer research.

NL-103 is an inhibitor of histone deacetylases (HDACs) and Hedgehog, with the IC₅₀ values ​​of 21.3 nM, 57 nM, 74 nM, and 680 nM for HDAC1, HDAC2, HDAC3, and HDAC6, respectively. NL-103 can downregulate the expression of Gli2. NL-103 can be used in anti-cancer research.

A2AAR/HDAC-IN-1 (compound 14c) is an orally active, potent and balanced A_2AAR/HDAC dual inhibitor, with a K_i of 163.5 nM for A_2AAR and an IC₅₀ of 145.3 nM for HDAC1. A2AAR/HDAC-IN-1 shows anticancer activity.

NB512 (compound 39a) is a dual inhibitor for BET and HDAC, which exhibits a efficient binding affinity with BRD4 bromodomains and HDAC1/2, with EC₅₀s of 100-400 nM. NB512 exhibits an anti-proliferative activity towards cancer cells PaTu8988T and NMC.

Rodin-C is a selective HDAC inhibitor with IC₅₀s of 0.059, 0.18   and 5.39 μM for HDAC1, HDAC2 and HDAC11, respectively, over HDAC3-10. Rodin-C significantly inhibits the HDAC-CoREST complex with low hematological toxicity. Rodin-C can be used for neurologic disorders such as Alzheimer’s disease research.

HDAC6-IN-82 is a selective HDAC6 inhibitor with an IC₅₀ of 4.9 nM against HDAC6. HDAC6-IN-82 inhibits HDAC1 (112 nM), HDAC2 (737 nM), HDAC3 (623 nM), HDAC8 (1140 nM), HDAC10 (91.4 nM) and HDAC11 (219 nM). HDAC6-IN-82 reduces cancer cell viability, induces cell cycle arrest, triggers apoptosis, and increases the acetylation levels of H3K9 and α-tubulin. HDAC6-IN-82 can be used in cancer-related research such as leukemia.

HDAC-IN-51 is a potent histone deacetylase (HDAC) inhibitor with IC₅₀ values of 0.32, 0.353, 0.431, 0.515, and 85.4 μM for HDAC10, HDAC1, HDAC2, HDAC3 and HDAC11, respectively. HDAC-IN-51 induces cell cycle arrest and apoptosis, modulating cell cycle-/apoptosis-related miRNAs expression. HDAC-IN-51 can be used in research of cancer.

HDAC6-IN-61 (Compound 4e) is a HDAC6 inhibitor (IC₅₀: 73 nM) with selectivity over other HDAC isoforms. HDAC6-IN-61 is also a GPR40 activator. HDAC6-IN-61 increases acetylated tubulin and ERK phosphorylation levels. HDAC6-IN-61 can be used for research of neuroinflammation such as Alzheimer's disease.

HDAC-IN-91 is a multiple inhibitor of HDAC (IC₅₀ = 134.22 nM for HDAC1, 66.29 nM for HDAC2), carbonic anhydrase (CA) (K_i = 72.03 nM for CA IX, 50.76 nM for XII), and tubulin polymerization ( IC₅₀ = 2.56 μM). HDAC-IN-91 inhibits PARP1 and increases the Bax/Bcl-2 ratio. HDAC-IN-91 blocks the cell cycle at the G2/M phase and induces apoptosis through a mitochondrial apoptosis activation mechanism. HDAC-IN-91 can exert potent cytotoxic activity through tubulin polymerization inhibition. HDAC-IN-91 can be used in breast, colorectal, cervical and lung cancer research.

HDAC-IN-57 is an orally active inhibitor of histone deacetylases (HDAC), with IC₅₀s of 2.07 nM, 4.71 nM, 2.4 nM and 107 nM for HDAC1, HDAC2, HDAC6, HDAC8, respectively. HDAC-IN-57 can inhibits LSD1, with IC₅₀ of 1.34 μΜ. HDAC-IN-57 induces apoptosis, and has anti-tumor activity.

HDAC-IN-98 is a HDAC1, HDAC2, HDAC3 inhibitor (one of the most selective class I HDAC inhibitors) with human IC₅₀ values of 41.2 nM, 52.5 nM, and 74.3 nM respectively. HDAC-IN-98 induces H3K9 acetylation, p21 upregulation, G2/M arrest, cell apoptosis, has strong antiproliferative effects in colorectal cancer cells, low toxicity in healthy colon epithelium, modulates short-term in vitro effects via autophagy, and shows strong antitumor efficacy in vivo in the chorioallantoic membrane model (CAM) assay. HDAC-IN-98 can be used for the research of colorectal cancer.

PIM-1/HDAC-IN-2 is a robust PIM/HDAC inhibitor (IC₅₀ = 0.11 μM in MV4-11cells), which exerts a synergistic antiproliferative effect through a dual mechanism of inhibiting PIM1 kinase and selectively inhibiting HDAC6. PIM-1/HDAC-IN-2 induces cell apoptosis. PIM-1/HDAC-IN-2 remarkably induces the cleavage of PARP, thereby initiating the arrest of the cell cycle in G1 phase and a reduction in S phase. PIM-1/HDAC-IN-2 demonstrates significant anticancer efficacyin the MV4-11 xenograft model without notable toxicity^[1]_.

NN-390 is a potent and selective HDAC6 inhibitor, with an IC₅₀ of 9.8 nM. NN-390 penetrates the blood-brain barrier (BBB). NN-390 shows study potential in metastatic Group 3 MB (medulloblastoma).

HDAC-IN-104 is a potent and selective class I Histone deacetylases (HDAC) inhibitor with an IC₅₀ of 25 nM. HDAC-IN-104 exerts potent antiproliferative and antitumor effects by inhibiting glycolysis and OXPHOS via blockade of the PI3K/AKT signaling pathway, and these effects are synergistically enhanced when combined with the FMS-like tyrosine kinase 3 (FLT3) inhibitor Quizartinib (AC220) (HY-13001). HDAC-IN-104 induces significant early and late apoptosis. HDAC-IN-104 can be used for acute myeloid leukemia (AML) research.

HDAC8-IN-17 is a histone deacetylase 8 inhibitor with human IC₅₀ values of 0.08 μM, 0.44 μM, and 1.9 μM, and high selectivity over HDAC1, HDAC2, HDAC3, and HDAC6. HDAC8-IN-17 exhibits slow-binding, reversible uncompetitive inhibition via allosteric binding to the enzyme-substrate complex. HDAC8-IN-17 induces selective hyperacetylation of SMC3. HDAC8-IN-17 can be used for the research of cancer.

PARP-1/HDAC-IN-1 is a PARP-1/HDAC6 dual targeting inhibitor with IC₅₀s of 68.90 nM and 510 nM, respectively. PARP-1/HDAC-IN-1 displays remarkable anticancer, anti-migration and anti-angiogenesis activities.