R59022 (R-59022; DKGI-I) is a novel and potent DGKalpha inhibitor and serotonin receptor antagonist. It inhibits diacylglycerol kinase with IC50 of 2.8 μM.
Physicochemical Properties
| Molecular Formula | C27H26FN3OS |
| Molecular Weight | 459.58 |
| Exact Mass | 459.178 |
| CAS # | 93076-89-2 |
| Related CAS # | R 59-022 hydrochloride;93076-98-3 |
| PubChem CID | 3012 |
| Appearance | White to off-white solid powder |
| Density | 1.26g/cm3 |
| Boiling Point | 619.8ºC at 760mmHg |
| Flash Point | 328.6ºC |
| Index of Refraction | 1.654 |
| LogP | 5.281 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 5 |
| Heavy Atom Count | 33 |
| Complexity | 868 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | O=C1N2C(SC=C2)=NC(C)=C1CCN1CC/C(=C(\C2C=CC(F)=CC=2)/C2C=CC=CC=2)/CC1 |
| InChi Key | MFVJXLPANKSLLD-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C27H26FN3OS/c1-19-24(26(32)31-17-18-33-27(31)29-19)13-16-30-14-11-22(12-15-30)25(20-5-3-2-4-6-20)21-7-9-23(28)10-8-21/h2-10,17-18H,11-16H2,1H3 |
| Chemical Name | 6-[2-[4-[(4-fluorophenyl)-phenylmethylidene]piperidin-1-yl]ethyl]-7-methyl-[1,3]thiazolo[3,2-a]pyrimidin-5-one |
| Synonyms | R59022 R 59022 R-59022 |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | 59-022 (1 minute, 10 μM) strengthens the aggregation [2]. R 59-022 (30 uM, 0–60 minutes) causes basophils to release more normetins [3]. In HeLa and U87 cells, R 59-022 (40 uM, 30 minutes) activates PKC [4]. In Vero cells, R 59-022 (0-10 uM, 4 hours) bursts EBOV [5]. |
| ln Vivo | The median survival of SCID mice transplanted with U87 GBM cells was significantly increased by R 59-022 (2 mg/kg, intraperitoneal injection, 12 days) [6]. |
| Cell Assay |
Western Blot Analysis [4] Cell Types: HeLa Cell Tested Concentrations: 40 uM Incubation Duration: 30 minutes Experimental Results: Phosphorylation of PKC downstream targets increased approximately 2.5-fold. |
| Animal Protocol |
Animal/Disease Models: SCID (severe combined immunodeficient) mouse implanted with U87 GBM cells [6] Doses: 10 mg/kg Route of Administration: intraperitoneal (ip) injection Experimental Results: Median survival increased and tumor volume diminished. |
| References |
[1]. R 59 022, a diacylglycerol kinase inhibitor. Its effect on diacylglycerol and thrombin-induced C kinase activation in the intact platelet. J Biol Chem. 1985 Dec 15;260(29):15762-70. [2]. 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]. 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]. Dual activities of ritanserin and R59022 as DGKα inhibitors and serotonin receptor antagonists. Biochem Pharmacol. 2017 Jan 1;123:29-39. [5]. A Diacylglycerol Kinase Inhibitor, R-59-022, Blocks Filovirus Internalization in Host Cells. Viruses. 2019 Mar 1;11(3). pii: E206. [6]. 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. |
| Additional Infomation | 6-[2-[4-[(4-fluorophenyl)-phenylmethylidene]-1-piperidinyl]ethyl]-7-methyl-5-thiazolo[3,2-a]pyrimidinone is a diarylmethane. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~62.5 mg/mL (~135.99 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.44 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.44 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (5.44 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1759 mL | 10.8795 mL | 21.7590 mL | |
| 5 mM | 0.4352 mL | 2.1759 mL | 4.3518 mL | |
| 10 mM | 0.2176 mL | 1.0879 mL | 2.1759 mL |