hdac8-in-1

MDK-7933 (HDAC8-IN-1) is a HDAC8 inhibitor with an IC50 of 27.2 nM in cancer cell lines. MDK-7933 shows antiproliferative effects toward several human lung cancer cell lines (A549, H1299, and CL1-5). HDAC8-IN-1 exhibits cytotoxicity against human lung CL1-5 cells without significant cytotoxicity for normal IMR-90 cells[1].

HDAC8 BRPF1-IN-1 (Compound 23a) is a dual inhibitor targeting human HDAC8 (IC50: 443 nM) and human BRPF1 (Kd: 67 nM), with low in vitro activity against HDAC1 and HDAC6.

HDAC8-IN-12 (compound 5k), a non-hydroxamic acid derivative, serves as a selective HDAC8 inhibitor with an IC 50 of 0.12 nM and demonstrates potent efficacy against breast cancer. This compound enhances anti-tumor immunity by activating T cells, elevating M1 macrophage levels, and reducing M2 macrophage proportions. In an orthotopic mouse model of breast cancer, HDAC8-IN-12, administered at 50 mg kg, effectively suppresses tumor growth.

HDAC8-IN-11 is a PROTAC target protein ligand.

HDAC8-IN-10 (compound 15) serves as a potent inhibitor of HDAC8, exhibiting an IC50 value of 7.6 nM. It also acts as a ligand for the HDAC8 target protein, utilized in the synthesis of PROTAC YX862.

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.

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.

Fibrostat (Compound 5n) is a selective HDAC6 inhibitor that exerts antifibrotic effects by hindering HDAC6 activity, with an IC50 value of 63 nM for HDAC6. It exhibits superior selectivity over HDAC1, HDAC3, HDAC5, HDAC8, HDAC10, and HDAC11. Fibrostat effectively reduces the expression of fibrosis markers, fibronectin and collagen 1, in fibroblasts. It shows no toxicity in rat perfused heart and zebrafish larvae studies. Fibrostat holds promise for research on fibrosis-related diseases.

Ebselen oxide (EB-2), a novel variant of HER2 inhibitor for HER2-positive cancers, is an EB-1 analog with antibacterial and antifungal activity, and has shown cytoprotective effects in vitro in addition to cytoprotective effects against HN2.Ebselen oxide inhibits alginate production by Pseudomonas aeruginosa and inhibits HDAC1, HDAC3, HDAC3, and HDAC3. Ebselen oxide inhibits alginate production by Pseudomonas aeruginosa, inhibits HDAC1, HDAC3, HDAC4, HDAC5, HDAC6, HDAC7, HDAC8, and HDAC9, and can be used in the study of fungal infections.

HDAC6-IN-3 (Compound 14) is a potent anti-prostate cancer agent that acts as an orally active inhibitor of HDAC6. It has IC50 values ranging from 0.02-1.54 μM for HDAC1, HDAC2, HDAC3, HDAC6, HDAC8, and HDAC10. Additionally, HDAC6-IN-3 also demonstrates effective inhibition of MAO-A (IC50 = 0.79 μM) and LSD1 [1].

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].

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].

HDAC8-IN-2 (compound 5o) is a potent HDAC8 inhibitor with IC50 values of 0.27 μM and 0.32 μM for smHDAC8 (Schistosoma mansoni histone deacetylase 8) and hHDAC8, respectively. It effectively kills schistosome larvae and significantly reduces egg laying in adult worm pairs [1].

HDAC6 8 BRPF1-IN-1 is a dual inhibitor targeting HDAC6, HDAC8, and the bromodomain and PHD finger containing protein 1 (BRPF1). It exhibits inhibitory activity against HDAC1, HDAC6, and HDAC8 with IC50 values of 797 nM, 344 nM, and 908 nM, respectively, and inhibits BRPF1 with a Kd value of 175.2 nM. This compound is utilized in cancer research [1].

HDAC8-IN-3 (compound P19) is a highly potent HDAC8 inhibitor with an IC50 value of 9.3 μM, inducing thermal stabilization, cytotoxicity, and apoptosis specifically in leukemic cell lines [1].

HDAC2-IN-1 (Compound 17) is an orally active, competitive HDAC2 inhibitor (IC50: 0.5 μM) that crosses the blood-brain barrier and also inhibits HDAC1 (IC50: 1.61 μM) and HDAC8 (IC50: 0.98 μM).

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.

SZUH280 is a potent, selective PROTAC (proteolysis targeting chimera) HDAC8 (histone deacetylase 8) degrader, demonstrating a DC50 of 0.58 μM in A549 cells. It induces apoptosis in cancer cells and impedes DNA damage repair, thereby enhancing cellular radiosensitization [1].

HDAC6-IN-17 (compound 5b) is a potent HDAC6 inhibitor with IC50 values of 150 nM for HDAC6, 1400 nM for HDAC8, and 2300 nM for HDAC4, demonstrating cytotoxic activity against human cancer cell lines and being utilized in cancer research [1].

HDAC8-IN-5 (Compound 6a), with an inhibitory concentration (IC50) of 28 nM, is a potent HDAC8 inhibitor suitable for cancer research [1].

Tubulin HDAC-IN-3 (compound 12a) is a potent dual inhibitor of tubulin polymerization and HDAC1 8, with IC50 values of 5.4 μM for tubulin polymerization, and 0.155 and 0.177 μM for HDAC1 and HDAC8, respectively. It obstructs the cell cycle, triggers apoptosis, and suppresses colony formation [1].

HDAC8-IN-4 is a selective HDAC8 inhibitor with IC50 values of 0.15 μM for HDAC8 and 12 μM for HDAC3 [1].

HDAC-IN-62 (Compound 5), an HDAC inhibitor, exhibits IC50 values of 0.78, 1.0, and 1.2 μM for HDAC6, HDAC8, and HDAC11, respectively. This compound suppresses microglial activation via autophagy induction and reduces nitric oxide production, demonstrating anti-inflammatory and antidepressant properties. Additionally, HDAC-IN-62 has been shown to inhibit microglial activation in mouse brains [1].