hdac 1

PI3K/HDAC-IN-1 is a potent dual inhibitor of PI3K and HDAC, with IC50 values of 8.1 nM and 1.4 nM, respectively.

mTOR/HDAC-IN-1 (Compound 50) is a dual inhibitor of mTOR and HDAC, with IC50 values of 0.49 nM and 0.91 nM, respectively, holding potential as an anti-cancer agent [1].

mTOR HDAC-IN-1 HCl is a potent dual inhibitor of mTOR and HDAC with potential anti-inflammatory, anti-proliferative, autophagy and apoptosis-inducing effects for cancer research.

FLT3 HDAC-IN-1 is a dual inhibitor targeting FLT3 and HDAC, with IC50 values of 30.4 nM for FLT3 and 52.4, 14.7 nM for HDAC1 3, respectively. It induces apoptosis in MV-4-11 cells and exhibits antiproliferative effects against BaF3 cells transformed by FLT3 mutations. FLT3 HDAC-IN-1 is useful for research on refractory solid tumors and hematological malignancies.

DNMT1 HDAC-IN-1 (compound (R)-23a), a potent dual inhibitor targeting both DNMT1 and HDAC, exhibits impressive inhibitory effects specifically on HDAC1 (HDAC1:IC50=0.05 μM), a major HDAC isoform that interacts with DNMT1 across multiple protein complexes involved in the transcriptional silencing of TSGs. This compound has been shown to remodel the tumor immune microenvironment and induce tumor regression, effectively reversing cancer-specific epigenetic abnormalities.

LSD1 HDAC-IN-1 (compound 2) serves as an effective inhibitor of both HDAC and LSD1, demonstrating IC50 values of 0.125 nM, 0.373 nM, 0.0118 nM, 0.103 nM, and 0.571 μM for HDAC1, HDAC2, HDAC6, HDAC8, and LSD1 respectively. This compound plays a crucial role in cancer research.

ROCK HDAC-IN-1 (Compound 10h) serves as an orally effective inhibitor of ROCK HDAC. This compound suppresses ROCK1 2 (IC50: 254.9 nM, 58.18 nM) and HDAC1 2 3 6 8 (IC50: 9.09, 8.03, 6.26, 0.41, 7.69 nM). It stimulates the activation of DAMPs, notably calreticulin (CRT) exposure and HMGB1 release, suggesting its potential as an inducer of immunogenic cell death (ICD). ROCK HDAC-IN-1 exhibits antiproliferative effects against breast cancer cells (IC50: 0.37 μM for MDA-MB-231 cells), inhibits tumor growth, activates T cells, and shows no significant toxicity.

CDK4 6 HDAC-IN-1 (Compound N14) is a dual-target inhibitor of CDK4 6 and HDAC, with IC50 values of 7.23 nM for CDK4, 13.20 nM for CDK6, 55.66 nM for HDAC1, and 48.38 nM for HDAC6. It induces apoptosis and G0 G1 phase arrest through the HDAC-p21-CDK signaling pathway and can inhibit hepatocellular carcinoma.

PD-L1 HDAC-IN-1 (Compound 14) is an inhibitor of PD-L1 and HDAC, effectively blocking PD-1 PD-L1 interaction as well as HDAC2 and HDAC3 with IC50 values of 88.10, 27.98, and 14.47 nM, respectively. It exhibits mild cytotoxicity in MCF-7 cells (IC50=19.34 μM) and enhances the expression of PD-L1 and CXCL10, promoting antitumor immune responses by recruiting T cell infiltration into the tumor microenvironment (TME).

HDAC/PSMD14-IN-1 is a derivative of gambogic acid. It serves as an orally active dual inhibitor targeting PSMD14 and HDAC1, with IC50 values of 238.7 nM and 141.2 nM, respectively. The compound exhibits significant cytotoxicity against ESCC cell lines (IC50: 30-250 nM) and effectively reverses epithelial-mesenchymal transition (EMT). Additionally, HDAC/PSMD14-IN-1 can induce apoptosis. In KYSE30 cell xenograft models in mice, it displays antitumor activity. HDAC/PSMD14-IN-1 is useful for researching esophageal cancer treatment.

EGFR/HDAC-IN-1 (Compound 22c2) is a potent dual inhibitor of epidermal growth factor receptor (EGFR) and histone deacetylase (HDAC), exhibiting IC50 values of 4.81 nM for EGFR, 119.4 nM for HDAC1, and 354.8 nM for HDAC3. It disrupts the EGFR signaling pathway and alters histone acetylation status, thereby inhibiting tumor cell proliferation. EGFR/HDAC-IN-1 is a promising candidate for research in non-small cell lung cancer (NSCLC).

ALK/HDAC-IN-1 is a dual inhibitor that targets both ALK and HDAC6, demonstrating IC50 values of 16 nM and 1.03 μM, respectively. This compound exhibits anti-tumor activity.

GSK-3β/HDAC-IN-1 (Compd 4) is a pioneering non-ATP competitive inhibitor that can penetrate the blood-brain barrier, targeting glycogen synthase kinase 3β/histone deacetylases (GSK-3β/HDACs). It exhibits IC50 values of 0.142 μM for GSK-3β, 0.03 μM for HDAC2, and 0.045 μM for HDAC6. GSK-3β/HDAC-IN-1 is utilized in Alzheimer's research.

NMDAR/HDAC-IN-1 (Compound 9d) is a potent dual inhibitor of N-methyl-D-aspartate receptors (NMDARs) and histone deacetylases (HDACs), with a high affinity for NMDARs (Ki = 0.59 μM) and significant inhibitory effects on various HDAC isoforms, including HDAC1, HDAC2, HDAC3, HDAC6, and HDAC8 with IC50 values of 2.67 μM, 8.00 μM, 2.21 μM, 0.18 μM, and 0.62 μM, respectively; additionally, it efficiently crosses the blood-brain barrier [1].

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

Tubulin/HDAC-IN-1 is a dual inhibitor of tubulin and HDAC8, interacting with tubulin via CH/π interactions and with HDAC8 through hydrogen bonds. It effectively inhibits tubulin polymerization and selectively targets HDAC8 with an IC50 of 150 nM. Additionally, Tubulin/HDAC-IN-1 demonstrates cytotoxicity against various human cancer cells, induces cell cycle arrest in the G2/M phase, and triggers cell apoptosis, making it valuable for studying hematologic and solid tumors, including neuroblastoma and leukemia [1].

CDK/HDAC-IN-1 exhibits potent inhibitory activity towards CDK2/4/6 and HDAC6, with IC50 values of 60.9 ± 2.9 nM, 276 ± 22.3 nM, 27.2 ± 4.2 nM, and 128.6 ± 0.4 nM, respectively.

MAO A/HDAC-IN-1 is an effective dual inhibitor of monoamine oxidase A (MAO A) and HDAC, suitable for glioma research.

PARP-1/HDAC-IN-1 is an effective dual inhibitor of PARP-1 and HDAC6, with IC50 values of 68.90 nM and 510 nM, respectively. PARP-1/HDAC-IN-1 exhibits anti-cancer, anti-migration, and anti-angiogenesis activities.

A2AAR/HDAC-IN-1 (compound 14c) is an orally active, balanced dual inhibitor of A2AAR (Ki: 163.5 nM) and HDAC1 (IC50: 145.3 nM).

Snail/HDAC-IN-1 is a Snail/HDAC inhibitor with antimicrobial and anticancer activity, known to reduce Snail protein expression and induce apoptosis, making it useful for the study of solid tumors.

Top/HDAC-IN-1 is a dual topoisomerase (Top)/HDAC inhibitor that acts on HDAC1 (IC50: 18 nM), HDAC2 (IC50: 230 nM), HDAC3 (IC50: 790 nM), HDAC6 (IC50: 87 nM) and HDAC8 (IC50: 5250 nM). Top/HDAC-IN-1 exhibited potent antitumor effects on HCT116 cells (IC50: 180 nM), blocked the cell cycle of HCT116 cells in G2 phase, and effectively induced apoptosis.

HDAC/Top-IN-1 is a broad-spectrum, orally active dual HDAC/Top inhibitor that acts on HDAC1 (IC50: 0.036 μM), HDAC2 (IC50: 0.14 μM), HDAC3 (IC50: 0.059 μM), HDAC6 (IC50: 0.089 μM) and HDAC8 ( IC50: 9.8 μM). HDAC/Top-IN-1 was able to block HEL cells in S-phase and effectively induce apoptosis.

PDE5/HDAC-IN-1 is a potent inhibitor of phosphodiesterase 5 (PDE5) and HDAC, with IC50 values of 46.3 nM and 14.5 nM, respectively.