R59022 | CAS#93076-89-2 | DGKalpha inhibitor

MedKoo Cat#: 561705 | Name: R59022

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Description:

WARNING: This product is for research use only, not for human or veterinary use.

R59022 is a DGKalpha inhibitor and serotonin receptor antagonist. Treatment of rice seedlings with the R59022 increases the level of DAG and decreases PA, which also restores the root phenotype of OsDGK1-overexpressing seedlings close to that of the WT.

Chemical Structure

R59022

CAS#93076-89-2

Theoretical Analysis

MedKoo Cat#: 561705

Name: R59022

CAS#: 93076-89-2

Chemical Formula: C27H26FN3OS

Exact Mass: 459.1781

Molecular Weight: 459.58

Elemental Analysis: C, 70.56; H, 5.70; F, 4.13; N, 9.14; O, 3.48; S, 6.98

Price and Availability

Size	Price	Availability
5mg	USD 375.00	2 weeks
10mg	USD 600.00	2 weeks
50mg	USD 1,350.00	2 weeks

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Related CAS #

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Synonym

R59022; R-59022; R 59022;

IUPAC/Chemical Name

6-[2-[4-[(4-Fluorophenyl)-phenylmethylidene]piperidin-1-yl]ethyl]-7-methyl-[1,3]thiazolo[3,2-a]pyrimidin-5-one

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

SMILES Code

O=C1C(CCN2CC/C(CC2)=C(C3=CC=C(F)C=C3)\C4=CC=CC=C4)=C(C)N=C5N1C=CS5

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

R59022 is a DGK inhibitor (IC50 = 2.8 µM), which results in increased DAG-dependent PKC activity and potentiates aggregation of thrombin-stimulated platelets. R59022 also blocks vascular contraction induced by the thromboxane analog U-46619. At 10 µM, R-59-022 induces apoptosis in glioblastoma cells without being toxic to non-cancerous cells.

In vitro activity:

This study reports that R59022 blocks Ebola virus glycoprotein -mediated entry into Vero cells and bone marrow-derived macrophages. This suggests that R59022 could be used to investigate macropinocytic uptake of filoviruses and could be a starting point for the development of pan-filoviral therapeutics. Reference: Viruses. 2019 Mar 1;11(3):206. https://pubmed.ncbi.nlm.nih.gov/30832223/

In vivo activity:

R59022 stimulated meiotic maturation of Xenopus laevis oocytes when applied extracellularly. Treatment of isolated membranes with R59022 resulted in inhibition of membrane-associated adenyl cyclas e activity that was not mimicked by DAG analogs. Thus, in addition to elevating oocyte levels of DAG, R59022 also has steroid-like actions. Reference: J Exp Zool. 1996 Apr 1;274(5):317-25. https://pubmed.ncbi.nlm.nih.gov/8618105/

	Solvent	mg/mL	mM
Solubility
	DMF	20.0	43.52
	Ethanol	5.0	10.88
	DMSO	5.0	10.88

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 459.58 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Stewart CM, Dorion SS, Ottenbrite MAF, LeBlond ND, Smith TKT, Qiu S, Fullerton MD, Kobasa D, Côté M. A Diacylglycerol Kinase Inhibitor, R-59-022, Blocks Filovirus Internalization in Host Cells. Viruses. 2019 Mar 1;11(3):206. doi: 10.3390/v11030206. PMID: 30832223; PMCID: PMC6466206. 2. Takita T, Konuma T, Hanazato M, Inoue H. Diacylglycerol kinase inhibitor R59022-induced autophagy and apoptosis in the neuronal cell line NG108-15. Arch Biochem Biophys. 2011 May 15;509(2):197-201. doi: 10.1016/j.abb.2011.02.007. Epub 2011 Feb 19. PMID: 21338572. 3. Sharma P, Yadav SK, Shah SD, Javed E, Lim JM, Pan S, Nayak AP, Panettieri RA Jr, Penn RB, Kambayashi T, Deshpande DA. Diacylglycerol Kinase Inhibition Reduces Airway Contraction by Negative Feedback Regulation of Gq-Signaling. Am J Respir Cell Mol Biol. 2021 Dec;65(6):658-671. doi: 10.1165/rcmb.2021-0106OC. PMID: 34293268; PMCID: PMC8641804. 4. Sadler SE, Frith T, Wasserman WJ. Analysis of R59022 actions in Xenopus laevis oocytes. J Exp Zool. 1996 Apr 1;274(5):317-25. doi: 10.1002/(SICI)1097-010X(19960401)274:5<317::AID-JEZ7>3.0.CO;2-S. PMID: 8618105.

In vitro protocol:

In vivo protocol:

1. Sharma P, Yadav SK, Shah SD, Javed E, Lim JM, Pan S, Nayak AP, Panettieri RA Jr, Penn RB, Kambayashi T, Deshpande DA. Diacylglycerol Kinase Inhibition Reduces Airway Contraction by Negative Feedback Regulation of Gq-Signaling. Am J Respir Cell Mol Biol. 2021 Dec;65(6):658-671. doi: 10.1165/rcmb.2021-0106OC. PMID: 34293268; PMCID: PMC8641804. 2. Sadler SE, Frith T, Wasserman WJ. Analysis of R59022 actions in Xenopus laevis oocytes. J Exp Zool. 1996 Apr 1;274(5):317-25. doi: 10.1002/(SICI)1097-010X(19960401)274:5<317::AID-JEZ7>3.0.CO;2-S. PMID: 8618105.

1: Gravina T, Boggio CMT, Gorla E, Racca L, Polidoro S, Centonze S, Ferrante D, Lunghi M, Graziani A, Corà D, Baldanzi G. Role of Diacylglycerol Kinases in Acute Myeloid Leukemia. Biomedicines. 2023 Jul 1;11(7):1877. doi: 10.3390/biomedicines11071877. PMID: 37509516; PMCID: PMC10377028. 2: Sharma P, Yadav SK, Shah SD, Javed E, Lim JM, Pan S, Nayak AP, Panettieri RA Jr, Penn RB, Kambayashi T, Deshpande DA. Diacylglycerol Kinase Inhibition Reduces Airway Contraction by Negative Feedback Regulation of Gq-Signaling. Am J Respir Cell Mol Biol. 2021 Dec;65(6):658-671. doi: 10.1165/rcmb.2021-0106OC. PMID: 34293268; PMCID: PMC8641804. 3: Lingelem ABD, Kavaliauskiene S, Halsne R, Klokk TI, Surma MA, Klose C, Skotland T, Sandvig K. Diacylglycerol kinase and phospholipase D inhibitors alter the cellular lipidome and endosomal sorting towards the Golgi apparatus. Cell Mol Life Sci. 2021 Feb;78(3):985-1009. doi: 10.1007/s00018-020-03551-6. Epub 2020 May 23. PMID: 32447426; PMCID: PMC7897626. 4: Sawatani T, Kaneko YK, Ishikawa T. Dual effect of reduced type I diacylglycerol kinase activity on insulin secretion from MIN6 β-cells. J Pharmacol Sci. 2019 Jun;140(2):178-186. doi: 10.1016/j.jphs.2019.06.001. Epub 2019 Jun 15. PMID: 31279581. 5: Derevyanchuk M, Kretynin S, Kolesnikov Y, Litvinovskaya R, Martinec J, Khripach V, Kravets V. Seed germination, respiratory processes and phosphatidic acid accumulation in Arabidopsis diacylglycerol kinase knockouts - The effect of brassinosteroid, brassinazole and salinity. Steroids. 2019 Jul;147:28-36. doi: 10.1016/j.steroids.2019.04.002. Epub 2019 Apr 11. PMID: 30981682. 6: Yuan S, Kim SC, Deng X, Hong Y, Wang X. Diacylglycerol kinase and associated lipid mediators modulate rice root architecture. New Phytol. 2019 Jul;223(1):261-276. doi: 10.1111/nph.15801. Epub 2019 Apr 20. PMID: 30887532. 7: Stewart CM, Dorion SS, Ottenbrite MAF, LeBlond ND, Smith TKT, Qiu S, Fullerton MD, Kobasa D, Côté M. A Diacylglycerol Kinase Inhibitor, R-59-022, Blocks Filovirus Internalization in Host Cells. Viruses. 2019 Mar 1;11(3):206. doi: 10.3390/v11030206. PMID: 30832223; PMCID: PMC6466206. 8: Velnati S, Ruffo E, Massarotti A, Talmon M, Varma KSS, Gesu A, Fresu LG, Snow AL, Bertoni A, Capello D, Tron GC, Graziani A, Baldanzi G. Identification of a novel DGKα inhibitor for XLP-1 therapy by virtual screening. Eur J Med Chem. 2019 Feb 15;164:378-390. doi: 10.1016/j.ejmech.2018.12.061. Epub 2018 Dec 26. PMID: 30611057; PMCID: PMC6599760. 9: McCloud RL, Franks CE, Campbell ST, Purow BW, Harris TE, Hsu KL. Deconstructing Lipid Kinase Inhibitors by Chemical Proteomics. Biochemistry. 2018 Jan 16;57(2):231-236. doi: 10.1021/acs.biochem.7b00962. Epub 2017 Nov 22. PMID: 29155586; PMCID: PMC5771882. 10: Boroda S, Niccum M, Raje V, Purow BW, Harris TE. 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. Epub 2016 Oct 28. PMID: 27974147; PMCID: PMC5164959. 11: Ruffo E, Malacarne V, Larsen SE, Das R, Patrussi L, Wülfing C, Biskup C, Kapnick SM, Verbist K, Tedrick P, Schwartzberg PL, Baldari CT, Rubio I, Nichols KE, Snow AL, Baldanzi G, Graziani A. Inhibition of diacylglycerol kinase α restores restimulation-induced cell death and reduces immunopathology in XLP-1. Sci Transl Med. 2016 Jan 13;8(321):321ra7. doi: 10.1126/scitranslmed.aad1565. PMID: 26764158; PMCID: PMC4918505. 12: Sovadinova I, Babica P, Böke H, Kumar E, Wilke A, Park JS, Trosko JE, Upham BL. Phosphatidylcholine Specific PLC-Induced Dysregulation of Gap Junctions, a Robust Cellular Response to Environmental Toxicants, and Prevention by Resveratrol in a Rat Liver Cell Model. PLoS One. 2015 May 29;10(5):e0124454. doi: 10.1371/journal.pone.0124454. Erratum in: PLoS One. 2015 Sep 01;10(9):e0137599. doi: 10.1371/journal.pone.0137599. PMID: 26023933; PMCID: PMC4449167. 13: Natalini PM, Mateos MV, Ilincheta de Boschero MG, Giusto NM. A novel light- dependent activation of DAGK and PKC in bovine photoreceptor nuclei. Exp Eye Res. 2014 Aug;125:142-55. doi: 10.1016/j.exer.2014.06.007. Epub 2014 Jun 17. PMID: 24950064. 14: Catacuzzeno L, Michelucci A, Sforna L, Aiello F, Sciaccaluga M, Fioretti B, Castigli E, Franciolini F. Identification of key signaling molecules involved in the activation of the swelling-activated chloride current in human glioblastoma cells. J Membr Biol. 2014 Jan;247(1):45-55. doi: 10.1007/s00232-013-9609-9. Epub 2013 Nov 16. PMID: 24240542. 15: Djafi N, Vergnolle C, Cantrel C, Wietrzyñski W, Delage E, Cochet F, Puyaubert J, Soubigou-Taconnat L, Gey D, Collin S, Balzergue S, Zachowski A, Ruelland E. The Arabidopsis DREB2 genetic pathway is constitutively repressed by basal phosphoinositide-dependent phospholipase C coupled to diacylglycerol kinase. Front Plant Sci. 2013 Aug 8;4:307. doi: 10.3389/fpls.2013.00307. PMID: 23964284; PMCID: PMC3737466. 16: Sato M, Liu K, Sasaki S, Kunii N, Sakai H, Mizuno H, Saga H, Sakane F. Evaluations of the selectivities of the diacylglycerol kinase inhibitors R59022 and R59949 among diacylglycerol kinase isozymes using a new non-radioactive assay method. Pharmacology. 2013;92(1-2):99-107. doi: 10.1159/000351849. Epub 2013 Aug 16. PMID: 23949095. 17: Natalini PM, Zulian SE, Ilincheta de Boschero MG, Giusto NM. Diacylglycerol kinase epsilon in bovine and rat photoreceptor cells. Light-dependent distribution in photoreceptor cells. Exp Eye Res. 2013 Jul;112:139-50. doi: 10.1016/j.exer.2013.04.012. Epub 2013 Apr 19. PMID: 23608524. 18: Dominguez CL, Floyd DH, Xiao A, Mullins GR, Kefas BA, Xin W, Yacur MN, Abounader R, Lee JK, Wilson GM, Harris TE, Purow BW. 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. Epub 2013 Apr 4. PMID: 23558954; PMCID: PMC3710531. 19: Tu-Sekine B, Goldschmidt H, Petro E, Raben DM. Diacylglycerol kinase θ: regulation and stability. Adv Biol Regul. 2013 Jan;53(1):118-26. doi: 10.1016/j.jbior.2012.09.007. Epub 2012 Sep 20. PMID: 23266086; PMCID: PMC3992713. 20: Martinez K, Shyamasundar S, Kennedy A, Chuang CC, Marsh A, Kincaid J, Reid T, McIntosh M. Diacylglycerol kinase inhibitor R59022 attenuates conjugated linoleic acid-mediated inflammation in human adipocytes. J Lipid Res. 2013 Mar;54(3):662-670. doi: 10.1194/jlr.M031211. Epub 2012 Dec 22. PMID: 23264678; PMCID: PMC3617941.