1346607-05-3
中文名稱
6-氯-5-(2'-羥基-3'-甲氧基-[1,1'-聯(lián)苯]-4-基)-3-(3-甲氧基苯基)-1H-吡咯并[3,2-D]嘧啶-2,4(3H,5H)-二酮
英文名稱
GSK621
CAS
1346607-05-3
分子式
C26H20ClN3O5
分子量
489.91
MOL 文件
1346607-05-3.mol
更新日期
2024/12/13 09:49:00
1346607-05-3 結(jié)構(gòu)式
基本信息
中文別名
6-氯-5-(2'-羥基-3'-甲氧基-[1,1'-聯(lián)苯]-4-基)-3-(3-甲氧基苯基)-1H-吡咯并[3,2-D]嘧啶-2,4(3H,5H)-二酮 英文別名
GSK621GSK621 (GSK 621
GSK621 >=98% (HPLC)
6-Chloro-5-(2'-hydroxy-3'-methoxy-[1,1'-biphenyl]-4-yl)-3-(3-methoxyphenyl)-1H-pyrrolo[3,2-d]pyrimidine-2,4(3H,5H)-dione
1H-Pyrrolo[3,2-d]pyrimidine-2,4(3H,5H)-dione, 6-chloro-5-(2'-hydroxy-3'-methoxy[1,1'-biphenyl]-4-yl)-3-(3-methoxyphenyl)-
所屬類別
醫(yī)藥中間體：雜環(huán)化合物物理化學(xué)性質(zhì)
密度1.41±0.1 g/cm3(Predicted)
儲(chǔ)存條件Sealed in dry,2-8°C
溶解度insoluble in H2O; insoluble in EtOH; ≥28.5 mg/mL in DMSO
酸度系數(shù)(pKa)9.01±0.40(Predicted)
形態(tài)結(jié)晶固體
顏色Off-white to light yellow
常見(jiàn)問(wèn)題列表
生物活性
GSK621 是特異性的 AMPK 激動(dòng)劑，其對(duì) AML 細(xì)胞系的IC50 值為13-30 μM。GSK621 可誘導(dǎo)自噬和凋亡。GSK621 可誘導(dǎo)eiF2α 磷酸化 (UPR 激活的一個(gè)標(biāo)志)。體外研究
GSK621 (30 μM) induces AMPKα T172, ACC (S79) and ULK1 (S555) phosphorylation.
GSK621 (30 μM) induces autophagy and apoptosis.
GSK621 treatment also induces PERK phosphorylation, a marker of ER stress, in AML cells.
Cell Proliferation Assay
| Cell Line: | MV4-11, OCI-AML3, OCI-AML2, HL-60, Kasumi, HEL, UT7, NB4, TF-1, KG1A, Nomo p28, SKM-1, U937, YHP1, MOLM-14, Mo7e, K562, MOLM-13, EOL-1, SET-2 AML cell lines. 0-30 μM. |
| Concentration: | 0-30 μM. |
| Incubation Time: | 4 d. |
| Result: |
IC
50
values ranged from 13 to 30 μM.
Reduced the proliferation of all 20 lines and increased apoptosis in 17 (85%) lines. |
Cell Autophagy Assay.
| Cell Line: | AML cell lines and primary AML samples. |
| Concentration: | 30 μM. |
| Incubation Time: | 24 h. |
| Result: | Induced the formation of numerous intracytoplasmic vacuoles including autophagosomes. |
體內(nèi)研究
GSK621 (30 mg/kg, ip twice daily) exhibits significant anti-tumor activity in MOLM-14 cells xenograft.
| Animal Model: | MOLM-14 cells xenografted into nude mice. |
| Dosage: | 30 mg/kg. |
| Administration: | IP twice daily. |
| Result: | Reduced leukemia growth and significantly extended survival compared to vehicle-treated animals or those treated with 10 mg/kg twice daily. |