SHP2/HDAC-IN-1 是一种变构的SHP2/HDAC双重抑制剂，IC50值分别为 20.4 nM (SHP2) 和 25.3 nM ( HDAC1)。SHP2/HDAC-IN-1 通过激活 T 细胞、增强抗原呈递功能和促进细胞因子分泌来触发抗肿瘤免疫反应。SHP2/HDAC-IN-1 可用于癌症的免疫治疗研究。
| 生物活性 | SHP2/HDAC-IN-1 is a dual allostericSHP2/HDACinhibitor withIC50values of 20.4 nM (SHP2) and 25.3 nM (HDAC1) respectively. SHP2/HDAC-IN-1 triggers efficient antitumor immunity by activating T cells, enhancing the antigen presentation function and promoting cytokine secretion. SHP2/HDAC-IN-1 can be used in the research ofcancer immunotherapy[1]. |
| IC50& Target[1] | HDAC1 25 nM (IC50) | HDAC2 79 nM (IC50) | HDAC3 233 nM (IC50) | HDAC6 27 nM (IC50) | SHP2 20.4 nM (IC50) |
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体外研究
(In Vitro) | SHP2/HDAC-IN-1 (compound 8t, 0-10 μM approximately, 72 h) inhibits the proliferation of BxPC-3, SW1990, AsPC-1and MV4-11 cells[1].
SHP2/HDAC-IN-1 (0.25-1 μM, 24 h) increases the acetylation of α-tubulin and histone H3 in MV4-11 cells[1].
SHP2/HDAC-IN-1 (0.25 μM, 24 h) inhibits cell cycle progression in the G1 phase of MV4-11 cells[1].
SHP2/HDAC-IN-1 (0.25 and 0.5 μM, 24 h) decreases the mitochondrial membrane potential and activats caspase-3[1].
SHP2/HDAC-IN-1 (2 h) shows good stability in in mouse liver microsome[1].
Cell Proliferation Assay[1] | Cell Line: | Pancreatic carcinoma (BxPC-3, SW1990, and AsPC-1), acute monocytic leukemia (MV4-11) | | Concentration: | 0-10 μM approximately | | Incubation Time: | 72 h | | Result: | Inhibited cell proliferation with IC50s range of 0.07 μM-3.92 μM. |
Western Blot Analysis[1] | Cell Line: | MV4-11 cells | | Concentration: | 0.25, 0.5, 1 μM | | Incubation Time: | 24 h | | Result: | Increased the acetylation of α-tubulin and histone H3.
Inhibited the phosphorylation level of ERK. |
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体内研究
(In Vivo) | SHP2/HDAC-IN-1 (compound 8t, 40 mg/kg, p.o.) inhibits tumor growth in MV4-11 and 4T1 tumor-bearing xenograft mice[1].
SHP2/HDAC-IN-1 (20 mg/kg p.o., 1 mg/kg i.v.) exhibits good maximum plasma concentrations in rats[1].
| Animal Model: | MV4-11 tumor-bearing xenograft mice[1] | | Dosage: | 40 mg/kg | | Administration: | Oral adminstration (p.o.), every day for 20 consecutive days. | | Result: | Delayed tumor progression with a tumor growth inhibition rate (TGI %) value of 64.0%, with no obvious signs of toxicity. |
| Animal Model: | 4T1 murine breast cancer model[1] | | Dosage: | 40 mg/kg | | Administration: | Oral adminstration (p.o.), every day for 12 consecutive days. | | Result: | Significantly decreased tumor burden with a TGI value of 72%.
Increased the proportions of CD4+ T cells and CD8+ T cells in the spleen.
Enhanced the proportion of mDCs in lymph nodes. |
| Animal Model: | Male Sprague-Dawley (SD) rats (Pharmacokinetic assay)[1] | | Dosage: | 20 mg/kg p.o., 1 mg/kg i.v. | | Administration: | Oral adminstration (p.o.) or intravenous injection (i.v.) | | Result: | Pharmacokinetic profile of SHP2/HDAC-IN-1 (compound 8t).
| dose (mg/kg) | T1/2(h) | Cmax(ng/mL) | Cl (mL/h/kg) | F (%) | |
| 20 (p.o.) | 5.32 | 1835 | | 21.42 | |
| 1 (i.v.) | 6.15 | 3517 | 326 | |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
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