| Hazard Information | Back Directory | [Uses]
HDAC-IN-53 is an orally active, and selective HDAC1-3 inhibitor with IC50 values of 47 nM, 125 nM, and 450 nM, respectively. HDAC-IN-53 does not inhibit class II HDACs (HDAC4, 5, 6, 7, 9; IC50>10 μM). HDAC-IN-53 induces caspase-dependent apoptosis. HDAC-IN-53 significantly inhibits the growth of human tumor xenografts in nude mice and murine tumor growth in immune-competent mice bearing MC38 colon cancer[1]. | [in vivo]
HDAC-IN-53 (60 or 120 mg/kg; PO; daily for 15 days) exerts antitumor activities by both direct tumor growth inhibition and indirect immune cell-mediated antitumor effect[1].
Pharmacokinetic Parameters of HDAC-IN-53 in Mice[1].
| IV (5 mg/kg) | PO (20 mg/kg) | | Tmax (h) | | 0.42 | | Cmax (ng/mL) | 8129 | 9558 | | AUC0-t (ng/mL?h) | 5864 | 15278 | | t1/2 (h) | 0.85 | 2.49 | | F (%) | | 65.1% |
| Animal Model: | C57BL/6 Mice or athymic nude mice (female, 6-8 weeks old) with MC38 cells[1] | | Dosage: | 60 or 120 mg/kg | | Administration: | PO; daily for 15 days | | Result: | Yielded TGI values of 60.3 and 87.6%, respectively.
Increased the percentage of CD4+ T cells.
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| [IC 50]
HDAC1: 47 nM (IC50); HDAC2: 125 nM (IC50); HDAC3: 450 nM (IC50); HDAC4: >10 μM (IC50); HDAC5: >10 μM (IC50); HDAC6: >10 μM (IC50); HDAC7: >10 μM (IC50); HDAC8: >10 μM (IC50); HDAC9: >10 μM (IC50) | [References]
[1] Nan Sun, et al. Design and Synthesis of Triazole-Containing HDAC Inhibitors That Induce Antitumor Effects and Immune Response. J Med Chem. 2023 Apr 13;66(7):4802-4826. DOI:10.1021/acs.jmedchem.2c01985 |
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