PRMT5-IN-19 (Compound 41) 是一种具有口服活性的非核苷PRMT5选择性抑制剂，IC50值为 23.9 nM (radioactive biochemical assay), 47 nM (AlphaLISA assay)。PRMT5-IN-19 可占据 PRMT5 中的 SAM-binding pocket 并封闭甲基转移酶的活性，选择性优于 PRMTs 和 PKMTs。PRMT5-IN-19 通过诱导细胞凋亡 (apoptosis) 来抑制细胞增殖，可用于癌症相关研究。
| 生物活性 | PRMT5-IN-19 (Compound 41) is an selective orally active non-nucleosidePRMT5inhibitor withIC50values of 23.9 nM (radioactive biochemical assay) and 47 nM (AlphaLISA assay). PRMT5-IN-19 can occupy theSAM-binding pocketinPRMT5and block methyltransferase activity, which displays good selectivity over other PRMTs and PKMTs. PRMT5-IN-19 inhibits cell proliferation by inducing cellapoptosis, and can be used for cancer-related research[1]. |
| IC50& Target | PRMT5 23.9 nM (IC50) | PRMT1 3.252 μM (IC50) | PRMT4 >20 μM (IC50) |
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体外研究
(In Vitro) | PRMT5-IN-19 (Compound 41, 5 days) has strong anti-proliferative effects against the A375 cell with anIC50value of 1.36 μM[1].
PRMT5-IN-19 shows higher selectivity for PRMT5 (IC50value of 23.9 nM) than other histone methyltransferases (PRMT1 and PRMT4), and PKMTS (EZH2, NSD2, MLL1, and MLL4)[1].
PRMT5-IN-19 binds with the SAM-binding pocket in PRMT5[1].
PRMT5-IN-19 (4-5 days) Inhibits proliferation of multiple cancer cell lines (A-375, CHL-1, SNU-423, SNU-449, MDA-MB-231, MDA-MA-453, MV-4-11, MOLM13) with IC50value ranging from 1.08 to 3.45 μM[1].
PRMT5-IN-19 inhibits arginine symmetrical dimethylation in A375 cells[1].
PRMT5-IN-19 (0-4 μM, 48 h) suppresses A375 cell proliferation by inducing apoptosis in a concentration-dependent manner[1].
Cell Proliferation Assay[1] | Cell Line: | A-375, CHL-1, SNU-423, SNU-449, MDA-MB-231, MDA-MA-453, MV-4-11, MOLM13 | | Concentration: | 0-10 μM | | Incubation Time: | 5 days | | Result: | Inhibited proliferation of multiple cancer cell lines with IC50value ranging from 1.08 to 3.45 μM. |
Western Blot Analysis[1] | Cell Line: | A-375 cells | | Concentration: | 0.5, 1, 2, 4,8 μM | | Incubation Time: | 48 h. | | Result: | Inhibited arginine symmetrical dimethylation in a dose-dependent manner. |
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体内研究
(In Vivo) | PRMT5-IN-19 (Compound 41, A375 xenograft model, 75 mg/kg/d, p.o., 19 days) has good PK properties and significant antitumor efficacy, without the obvious loss of body weight and visible toxicity[1].
| Animal Model: | A375 cell-derived nude mouse xenograft model[1]. | | Dosage: | 75 mg/kg/d | | Administration: | P.o., 19 days | | Result: | Had no effect on the body weight, displayed antitumor efficacy with a tumor growth inhibition (TGI) rate of 73% by inhibiting the methyltransferase activity of PRMT5. |
| Animal Model: | Rats and mice[1]. | | Dosage: | 10 mg/kg for p.o., 3 mg/kg for i.v | | Administration: | P.o., i.v. (Pharmacokinetic Analysis) | | Result: | Pharmacokinetic parameters for PRMT5-IN-19 in SD Rats and Micea,c[1].| species | PRMT5-IN-19 | T1/2(h) | Cmax (ng/mL) | CL (mL/min/kg) | F (%) | | rat | iv (3 mg/kg)/td> | 2.58 | | 310 | | | po (10 mg/kg)/td> | 7.51 | 8.22 | | 7.25 | | po (10 mg/kg)/td> | 2.95 | 27.7 | | 23.7 | | mouse | iv (3 mg/kg)/td> | 4.71 | | 153 | | | po (10 mg/kg)/td> | | 128 | Data Sheet (536 KB)产品使用指南 (1538 KB)
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