<Suppliers Price>

R 59-022 hydrochloride

Names

[ CAS No. ]:
93076-98-3

[ Name ]:
R 59-022 hydrochloride

Biological Activity

[Description]:

R 59-022 (DKGI-I) hydrochloride is a DGK inhibitor (IC50: 2.8 µM). R 59-022 hydrochloride inhibits the phosphorylation of OAG to OAPA. R 59-022 hydrochloride is a 5-HT Receptor antagonist, and activates protein kinase C (PKC). R 59-022 hydrochloride potentiates thrombin-induced diacylglycerol production in platelets and inhibits phosphatidic acid production in neutrophils[1][2][3][4].

[Related Catalog]:

Signaling Pathways >> Epigenetics >> PKC
Research Areas >> Cancer
Research Areas >> Infection
Research Areas >> Inflammation/Immunology
Signaling Pathways >> TGF-beta/Smad >> PKC
Signaling Pathways >> GPCR/G Protein >> 5-HT Receptor
Signaling Pathways >> Neuronal Signaling >> 5-HT Receptor

[Target]

PKC

serotonin

DGK:2.8 μM (IC50)


[In Vitro]

R 59-022 (10 μM，1 分钟) hydrochloride 增强血小板聚集[2]。 R 59-022 (30 μM，0-60 分钟) hydrochloride 增加嗜铬细胞中去甲肾上腺素的释放[3]。 R 59-022 (40 μM，30 分钟) hydrochloride 激活 HeLa 和 U87 细胞中的 PKC[4]。 R 59-022 (0-10 μM，4 小时) hydrochloride 阻断 EBOV GP 进入 Vero 细胞[5]。 Western Blot Analysis[4] Cell Line: HeLa cells Concentration: 40 uM Incubation Time: 30 min Result: Increased the phosphorylation of PKC downstream targets by about 2.5-fold.

[In Vivo]

R 59-022 (2 mg/kg，腹腔注射，12 天) hydrochloride 显着增加植入 U87 GBM 细胞的 SCID 小鼠的中位生存期[6]。 Animal Model: SCID mice implanted with U87 GBM cells[6] Dosage: 10 mg/kg Administration: Intraperitoneal injection (i.p.) Result: Increased median survival and decreased tumor volume.

[References]

[1]. de Chaffoy de Courcelles, D.C., et al. R 59 022, a diacylglycerol kinase inhibitor. Its effect on diacylglycerol and thrombin-induced C kinase activation in the intact platelet. J. Biol. Chem. 260(29), 15762-15770 (1985).  

[2]. Nunn DL, et al. A diacylglycerol kinase inhibitor, R59022, potentiates secretion by and aggregation of thrombin-stimulated human platelets. Biochem J. 1987 May 1;243(3):809-13.  

[3]. Jones JA, et al. Influence of phorbol esters, and diacylglycerol kinase and lipase inhibitors on noradrenalinerelease and phosphoinositide hydrolysis in chromaffin cells. Br J Pharmacol. 1990 Nov;101(3):521-6.  

[4]. Boroda S, et al. Dual activities of ritanserin and R59022 as DGKα inhibitors and serotonin receptor antagonists. Biochem Pharmacol. 2017 Jan 1;123:29-39.  

[5]. Stewart CM, et al. A Diacylglycerol Kinase Inhibitor, R-59-022, Blocks Filovirus Internalization in Host Cells. Viruses. 2019 Mar 1;11(3). pii: E206.  

[6]. Dominguez CL, et al. Diacylglycerol kinase α is a critical signaling node and novel therapeutic target in glioblastoma and other cancers. Cancer Discov. 2013 Jul;3(7):782-97.  

Chemical & Physical Properties

[ Molecular Formula ]:
C27H27ClFN3OS

[ Molecular Weight ]:
496.04

Related Compounds