| Identification | Back Directory | [Name]
GSK547 | [CAS]
2226735-55-1 | [Synonyms]
RIP1I GSK547 CPD3508 RIP1 inhibitor 547 RIP1 inhibitor GSK547 (S)-6-(4-(5-(3,5-Difluorophenyl)-4,5-dihydro-1H-pyrazole-1-carbonyl)piperidin-1-yl)pyrimidine-4-carbonitrile 4-Pyrimidinecarbonitrile, 6-[4-[[(5S)-5-(3,5-difluorophenyl)-4,5-dihydro-1H-pyrazol-1-yl]carbonyl]-1-piperidinyl]- | [Molecular Formula]
C20H18F2N6O | [MDL Number]
MFCD32062767 | [MOL File]
2226735-55-1.mol | [Molecular Weight]
396.39 |
| Chemical Properties | Back Directory | [Boiling point ]
578.3±60.0 °C(Predicted) | [density ]
1.43±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO:65.0(Max Conc. mg/mL);163.98(Max Conc. mM) | [form ]
Solid | [pka]
1.93±0.28(Predicted) | [color ]
White to off-white | [InChI]
InChI=1S/C20H18F2N6O/c21-15-7-14(8-16(22)9-15)18-1-4-26-28(18)20(29)13-2-5-27(6-3-13)19-10-17(11-23)24-12-25-19/h4,7-10,12-13,18H,1-3,5-6H2/t18-/m0/s1 | [InChIKey]
SJVGFKBLUYAEOK-SFHVURJKSA-N | [SMILES]
C1=NC(N2CCC(C(N3[C@H](C4=CC(F)=CC(F)=C4)CC=N3)=O)CC2)=CC(C#N)=N1 |
| Hazard Information | Back Directory | [Uses]
GSK547 (GSK'547) is a highly selective and potent inhibitor of receptor-interacting serine/threonine protein kinase 1 (RIPK1), inhibits macrophage-mediated adaptive immune tolerance in pancreatic cancer[1]. | [Biological Activity]
GSK'547 is a highly selective and potent inhibitor of RIP1 (RIPK1) with a 400-fold increase in oral exposure compared to GSK'963 in mouse pharmacokinetic studies. | [in vitro]
In vitro, treatment with GSK'547 directed bone marrow-derived macrophages to develop an immunogenic phenotype, with up-regulation of MHC-II, TNFa and IFNg expression, and decreased CD206, IL- 10 and TGFb expression. In addition, it also up-regulated STAT1 signaling and decreased STAT3, STAT5 and STAT6 signaling in bone marrow-derived macrophages. Macrophages treated with GSK'547 had stronger ability to capture antigens. | [in vivo]
Mice were given GSK'547 through food, the concentration of GSK'547 in vivo was stable within 24 hours, which was higher than the IC50 value in L929 cells. GSK'547 maintained high concentrations in vivo during the 6-week administration. GSK'547 was well tolerated with no obvious pathological features. In mice with in situ pancreatic ductal adenocarcinoma, It reduced tumor burden and prolonged survival compared to control and Nec-1s-treated groups. GSK'547 prevents established tumors and liver metastases. | [target]
| Target | Value | RIP1 () | table>[References]
[1] Wang W, et al. RIP1 Kinase Drives Macrophage-Mediated Adaptive Immune Tolerance in Pancreatic Cancer. Cancer Cell. 2018 Nov 12;34(5):757-774.e7. DOI:10.1016/j.ccell.2018.10.006 |
|
| Company Name: |
BOC Sciences
|
| Tel: |
16314854226 |
| Website: |
www.bocsci.com |
|
|
Tags:2226735-55-1
Related Product Information
|
|
1627856-64-7
1346572-63-1
1652591-81-5
1346547-00-9
1010411-21-8
929095-18-1
1628332-52-4
1622849-58-4
1616392-22-3
188591-46-0
1362154-70-8
|
安溪县|
革吉县|
临武县|
册亨县|
宁津县|
陆良县|
平乡县|
辽宁省|
新民市|
同心县|
米泉市|
西安市|
内江市|
县级市|
泾川县|
嫩江县|
南充市|
灵石县|
清流县|
三门峡市|
德庆县|
桐乡市|
星子县|
额敏县|
阿图什市|
竹溪县|
泗水县|
团风县|
潍坊市|
大安市|
怀安县|
夏河县|
贵州省|
武宣县|
石家庄市|
武功县|
青田县|
阿克陶县|
旺苍县|
阿拉善盟|
梁河县|
|