R 59-022 hydrochloride  (Synonyms: DKGI-I hydrochloride; Diacylglycerol kinase inhibitor I hydrochloride)

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].

R 59-022 (10 μM, 1 min) hydrochloride potentiates aggregation, but not shape change induced by sub-maximal concentrations of thrombin^[2].
R 59-022 (30 μM, 0-60 min) hydrochloride increases release of Noradrenaline in chromaffin cells^[3].
R 59-022 (40 μM, 30 min) hydrochloride activates PKC in HeLa and U87 cells^[4].
R 59-022 (0-10 μM, 4 h) hydrochloride blocks EBOV GP-mediated entry into Vero cells^[5].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

R 59-022 (2 mg/kg, i.p., 12 days) hydrochloride significantly increases median survival in SCID mice implanted with U87 GBM cells^[6].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

496.04

Solid

C₂₇H₂₇ClFN₃OS

93076-98-3

O=C1C(CCN(CC/2)CCC2=C(C3=CC=CC=C3)/C4=CC=C(F)C=C4)=C(C)N=C5N1C=CS5.[H]Cl

Room temperature in continental US; may vary elsewhere.

• [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).  [Content Brief]

  [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.  [Content Brief]

  [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.  [Content Brief]

  [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.  [Content Brief]

  [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.  [Content Brief]

  [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.  [Content Brief]