HDAC4 Inhibitor

SM-06-09 is a potent, highly selective, orally active tetrazolone-based HDAC6 inhibitor with an IC₅₀ value of 0.49 nM. SM-06-09 promotes tumor-associated macrophage (TAM) polarization toward an antitumor M1-like phenotype and enhances macrophage phagocytosis, antigen presentation, and T-cell activation. SM-06-09 remodels the tumor immune microenvironment, exhibits antitumor activity in melanoma models, and enhances the efficacy of anti-PD-1 immune checkpoint blockade.

HDAC6-IN-10 is a highly selective HDAC6 inhibitor with the IC₅₀ of 0.73 nM. HDAC6-IN-10 has 144~10941-fold selectivity over other HDAC isoforms. HDAC6-IN-10 shows anti-proliferative activities against multiple myeloma cells.

HDAC-IN-105 is a histone deacetylase (HDAC) inhibitor with binding to HDAC2 and HDAC4 isoforms. HDAC-IN-105 suppresses HDAC activity via binding within conserved HDAC catalytic pockets. HDAC-IN-105 induces G2/M phase cell cycle arrest. HDAC-IN-105 triggers mitochondrial dysfunction marked by loss of mitochondrial membrane potential. HDAC-IN-105 exhibits growth inhibition in triple-negative breast cancer cells and low toxicity toward normal cells. HDAC-IN-105 can be used for the research of triple-negative breast cancer.

MC2590 is a potent pyridine-containing histone deacetylase (HDAC) inhibitor. MC2590 is a inhibitor of HDAC1-3, -6, -8, and -10 (class I/IIb-selective inhibitor) with IC₅₀s of 0.015 μM-0.156 μM. MC2590 also inhibits HDAC isoforms HDAC4, HDAC5, HDAC7, HDAC9, HDAC11 with IC₅₀s of 1.35 μM-3.98 μM. MC2625 induces G2/M cell cycle arrest and modulates pro- and anti-apoptotic microRNAs towards apoptosis induction.

HDAC6 ligand-7 (Compound 16a) is a positron emission tomography (PET) tracer for the deacetylase 6 (HDAC6) enzyme with a K_d value of 1.66 nM. HDAC6 ligand-7 exhibits excellent HDAC6 inhibitory activity, with IC₅₀ values of 2.7 and 3.7 nM for hHDAC6 and mHDAC6, respectively, and has high selectivity for HDAC1/4/7/8. HDAC6 ligand-7 after being radioactively labeled with fluorine-18, [¹⁸F]HDAC6 ligand-7 shows varying degrees of radioactive uptake in PET, which can reflect the specific binding to HDAC6. HDAC6 ligand-7 can be used for the study of HDAC6 imaging.

C1A is a class I/II HDACs and sirtuin inhibitor with an IC₅₀ of 479 nM for HDAC6. C1A induces sustained acetylation of HDAC6 substrates, α-tubulin and HSP90. C1A shows srtong anticancer effcts, and induces apoptosis in cancer cells.

FLT3/HDAC-IN-3 is a dual inhibitor of FLT3 and HDAC. FLT3/HDAC-IN-3 potently inhibits FLT3 (IC₅₀ = 14 nM), HDAC1 (IC₅₀ = 27 nM), HDAC6 (IC₅₀ = 20 nM), and FLT3^D853Y (IC₅₀ = 55 nM), exhibits weak activity against HDAC8, and shows no activity against HDAC4. FLT3/HDAC-IN-3 possesses kinase selectivity, plasma stability, and stability in human liver microsomes. FLT3/HDAC-IN-3 demonstrates anti-proliferative effects in a variety of hematological malignancy cell lines. FLT3/HDAC-IN-3 shows efficacy in the Jeko-1 xenograft model without observed significant toxicity. FLT3/HDAC-IN-3 can be used in the study of hematological malignancies.

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.

HDAC6-IN-69 is a brain-penetrant and highly selective HDAC6 inhibitor with an IC₅₀ of 4.0 nM. HDAC6-IN-69 shows >176-fold against other HDAC isoforms. HDAC6-IN-69 engages the target in neuronal cells by dose-dependently upregulating acetylated α-tubulin in virto. HDAC6-IN-69 has neuroprotective effect and can be used for ischemic stroke research .

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.

KH-259 (compound 1) is a potent, selective and CNS-penetrant HDAC6 inhibitor, with an IC₅₀ of 0.26 μM. KH-259 has antidepressant effects in mice through the inhibition of HDAC6 in the brain. KH-259 can be used for neurodegenerative diseases research.

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]_.

G4/HDAC-IN-1 (compound a6) is a G4/HDAC dual-targeting compound. G4/HDAC-IN-1 inhibits intracellular HDAC activity with an IC₅₀ value of 1.1 μM, and induces G4 formation. G4/HDAC-IN-1 inhibits TNBC proliferation and tumor growth in TNBC xenograft model. G4/HDAC-IN-1 can be used for the research of cancer.

HDAC6-IN-63 (Compound 7) is an orally active HDAC6 inhibitor with an IC₅₀ of 145  nM. HDAC6-IN-63 inhibits the expression of Sp1 and RAD51, thereby inducing Caspase-dependent apoptosis. HDAC6-IN-63 has antitumor activity and sensitizes Etoposide (HY-13629) and Gemcitabine (HY-17026), promoting synergistic death of NSCLC cells through the inhibition of homologous recombination and non-homologous end joining (NHEJ) pathways involved in DNA DSB repair. HDAC6-IN-63 can be used for chemotherapy of cancers like NSCLC research.

HDAC ligand-5 is a template for the non-selective HDAC inhibitor Vorinostat (HY-10221). HDAC ligand-5 can serve as a ligand for target protein (Ligands for Target Protein for PROTAC) for the development of PROTAC HDAC degraders with antitumor activity. HDAC ligand-5 can be used for the synthesis of FF2049 (HY-168863).

HDAC6-IN-44 (compound H10) is a selective HDAC6 inhibitor with an IC₅₀ value of 8.97 nM. HDAC6-IN-44 can inhibit the idiopathic pulmonary fibrosis (IPF) phenotype and exhibits antifibrotic activity. Additionally, HDAC6-IN-44 reduces fibrogenesis in a bleomycin-induced pulmonary fibrosis mouse model and demonstrates good metabolic stability. HDAC6-IN-44 holds promise for research in the field of idiopathic pulmonary fibrosis.

JAK/HDAC-IN-2 is a potent 2-amino-4-phenylaminopyrimidine JAK/HDAC dual-target inhibitor. JAK/HDAC-IN-2 potently inhibits HDAC3/6 and JAK1/2 at nanomolar levels. JAK/HDAC-IN-2 has proapoptotic activity and inhibits histone deacetylation and STAT3 phosphorylation. JAK/HDAC-IN-2 presents remarkable antiproliferative activity in both hematological malignancies and solid cancers.

PIM-1/HDAC-IN-1 (compound 4d) is a PIM-1 inhibitor, with an IC₅₀ of 343.87 nM. PIM-1/HDAC-IN-1 has strong inhibitory activity and selectivity against HDAC 1 and HDAC 6, with IC₅₀ values of 63.65 and 62.39 nM, respectively. PIM-1/HDAC-IN-1 exhibits apoptosis inducing potential in MCF-7 cell lines. PIM-1/HDAC-IN-1 shows pre-G1 apoptosis and cell cycle arrest at G2/M phase.

HDAC6-IN-14 is a highly selective HDAC6 (HDAC) inhibitor with an IC₅₀ of 42 nM. HDAC6-IN-14 displays >100-fold selectivity over HDAC1/HDAC2/HDAC3/HDAC4.