| Identification | Back Directory | [Name]
5H-Thiazolo[3,2-a]pyrimidin-5-one, 6-[2-[4-[(4-fluorophenyl)phenylmethylene]-1-piperidinyl]ethyl]-7-methyl-, hydrochloride (1:1) | [CAS]
93076-98-3 | [Synonyms]
R 59-022 hydrochloride
5H-Thiazolo[3,2-a]pyrimidin-5-one, 6-[2-[4-[(4-fluorophenyl)phenylmethylene]-1-piperidinyl]ethyl]-7-methyl-, hydrochloride (1:1) | [Molecular Formula]
C27H27ClFN3OS | [MOL File]
93076-98-3.mol | [Molecular Weight]
496.04 |
| Hazard Information | Back Directory | [Uses]
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]. | [in vivo]
R 59-022 (2 mg/kg, i.p., 12 days) hydrochloride significantly increases median survival in SCID mice implanted with U87 GBM cells[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. |
| [IC 50]
PKC; serotonin; DGK: 2.8 μM (IC50) | [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). PMID:2999135
[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. DOI:10.1042/bj2430809
[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. DOI:10.1111/j.1476-5381.1990.tb14114.x
[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. DOI:10.1016/j.bcp.2016.10.011
[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. DOI:10.3390/v11030206
[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. DOI:10.1158/2159-8290.CD-12-0215 |
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