R 59949 | CAS#120166-69-0 | DGK inhibitor

MedKoo Cat#: 461069 | Name: R 59949

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Description:

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

R 59949 is a Diacylglycerol kinase (DGK) inhibitor.

Chemical Structure

R 59949

CAS#120166-69-0

Theoretical Analysis

MedKoo Cat#: 461069

Name: R 59949

CAS#: 120166-69-0

Chemical Formula: C28H25F2N3OS

Exact Mass: 489.1686

Molecular Weight: 489.58

Elemental Analysis: C, 68.69; H, 5.15; F, 7.76; N, 8.58; O, 3.27; S, 6.55

Price and Availability

Size	Price	Availability
5mg	USD 450.00	2 weeks
10mg	USD 700.00	2 Weeks
25mg	USD 1,100.00	2 Weeks

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Related CAS #

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Synonym

R 59949; R-59949; R59949;

IUPAC/Chemical Name

3-(2-(4-(bis(4-fluorophenyl)methylene)piperidin-1-yl)ethyl)-2-thioxo-2,3-dihydroquinazolin-4(1H)-one

InChi Key

ZCNBZFRECRPCKU-UHFFFAOYSA-N

InChi Code

InChI=1S/C28H25F2N3OS/c29-22-9-5-19(6-10-22)26(20-7-11-23(30)12-8-20)21-13-15-32(16-14-21)17-18-33-27(34)24-3-1-2-4-25(24)31-28(33)35/h1-12H,13-18H2,(H,31,35)

SMILES Code

O=C1N(CCN2CC/C(CC2)=C(C3=CC=C(F)C=C3)\C4=CC=C(F)C=C4)C(NC5=C1C=CC=C5)=S

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

>3 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:

R59949, with an IC50 of 300 nM, inhibits inducible nitric oxide production through decreasing transplasmalemmal L-arginine uptake in vascular smooth muscle cells. R59949 strongly inhibits type I DGK a and γ, and moderately attenuates type II DGK θ and κ.

In vitro activity:

Depression of lipid metabolism in β-cells has been indicated to be one of the causes of impaired insulin secretion in type 2 diabetes. In the pancreatic β-cell line MIN6, 1 μM R59949 enhanced glucose-induced [Ca2+]i oscillation in a PKC-dependent manner, while 10 μM R59949 suppressed [Ca2+]i oscillation and voltage-dependent Ca2+ channel activity in a PKC-independent manner. Reference: Yakugaku Zasshi. 2022;142(5):457-463. https://pubmed.ncbi.nlm.nih.gov/35491149/

In vivo activity:

This study examined the effect of R59949 on retinal neovascularization and its potential mechanism in an oxygen-induced retinopathy model. The findings suggest the possibility that R59949 suppressed retinal neovascular pathophysiology via PHD2/HIF-1α/VEGF pathway. Reference: J Mol Neurosci. 2015 May;56(1):78-88. https://pubmed.ncbi.nlm.nih.gov/25451596/

	Solvent	mg/mL	mM
Solubility
	DMF	33.0	67.40
	DMSO	33.0	67.40
	Ethanol	1.0	2.04

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 489.58 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. Kaneko YK, Sawatani T, Ishikawa T. [Involvement of Diacylglycerol Kinase on the Regulation of Insulin Secretion in Pancreatic β-Cells during Type 2 Diabetes]. Yakugaku Zasshi. 2022;142(5):457-463. Japanese. doi: 10.1248/yakushi.21-00176-2. PMID: 35491149. 2. Li J, Lu X, Wei L, Ye D, Lin J, Tang X, Cui K, Yu S, Xu Y, Liang X. PHD2 attenuates high-glucose-induced blood retinal barrier breakdown in human retinal microvascular endothelial cells by regulating the Hif-1α/VEGF pathway. Inflamm Res. 2022 Jan;71(1):69-79. doi: 10.1007/s00011-021-01518-2. Epub 2021 Nov 13. PMID: 34773469. 3. Yang L, Xu Y, Li W, Yang B, Yu S, Zhou H, Yang C, Xu F, Wang J, Gao Y, Huang Y, Lu L, Liang X. Diacylglycerol kinase (DGK) inhibitor II (R59949) could suppress retinal neovascularization and protect retinal astrocytes in an oxygen-induced retinopathy model. J Mol Neurosci. 2015 May;56(1):78-88. doi: 10.1007/s12031-014-0469-2. Epub 2014 Dec 2. PMID: 25451596. 4. Shimomura T, Nakano T, Goto K, Wakabayashi I. R59949, a diacylglycerol kinase inhibitor, inhibits inducible nitric oxide production through decreasing transplasmalemmal L-arginine uptake in vascular smooth muscle cells. Naunyn Schmiedebergs Arch Pharmacol. 2017 Feb;390(2):207-214. doi: 10.1007/s00210-016-1316-5. Epub 2016 Dec 1. PMID: 27909743.

In vitro protocol:

In vivo protocol:

1. Yang L, Xu Y, Li W, Yang B, Yu S, Zhou H, Yang C, Xu F, Wang J, Gao Y, Huang Y, Lu L, Liang X. Diacylglycerol kinase (DGK) inhibitor II (R59949) could suppress retinal neovascularization and protect retinal astrocytes in an oxygen-induced retinopathy model. J Mol Neurosci. 2015 May;56(1):78-88. doi: 10.1007/s12031-014-0469-2. Epub 2014 Dec 2. PMID: 25451596. 2. Shimomura T, Nakano T, Goto K, Wakabayashi I. R59949, a diacylglycerol kinase inhibitor, inhibits inducible nitric oxide production through decreasing transplasmalemmal L-arginine uptake in vascular smooth muscle cells. Naunyn Schmiedebergs Arch Pharmacol. 2017 Feb;390(2):207-214. doi: 10.1007/s00210-016-1316-5. Epub 2016 Dec 1. PMID: 27909743.

1: Singh BK, Lu W, Schmidt Paustian AM, Ge MQ, Koziol-White CJ, Flayer CH, Killingbeck SS, Wang N, Dong X, Riese MJ, Deshpande DA, Panettieri RA Jr, Haczku A, Kambayashi T. Diacylglycerol kinase ζ promotes allergic airway inflammation and airway hyperresponsiveness through distinct mechanisms. Sci Signal. 2019 Sep 3;12(597):eaax3332. doi: 10.1126/scisignal.aax3332. PMID: 31481522; PMCID: PMC6996596. 2: 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. 3: 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. 4: Noh MR, Jang HS, Song DK, Lee SR, Lipschutz JH, Park KM, Kim JI. Downregulation of exocyst Sec10 accelerates kidney tubule cell recovery through enhanced cell migration. Biochem Biophys Res Commun. 2018 Feb 5;496(2):309-315. doi: 10.1016/j.bbrc.2018.01.013. Epub 2018 Jan 8. PMID: 29326040. 5: Shimomura T, Nakano T, Goto K, Wakabayashi I. R59949, a diacylglycerol kinase inhibitor, inhibits inducible nitric oxide production through decreasing transplasmalemmal L-arginine uptake in vascular smooth muscle cells. Naunyn Schmiedebergs Arch Pharmacol. 2017 Feb;390(2):207-214. doi: 10.1007/s00210-016-1316-5. Epub 2016 Dec 1. PMID: 27909743. 6: Nakamura T, Kamishikiryo J, Morita T. Prazosin-stimulated release of hepatic triacylglyceride lipase from primary cultured rat hepatocytes is involved in the regulation of cAMP-dependent protein kinase through activation of the Ca(2+)/calmodulin-dependent protein kinase-II. Pharmacol Rep. 2016 Jun;68(3):649-53. doi: 10.1016/j.pharep.2016.02.001. Epub 2016 Feb 22. PMID: 27031052. 7: Yang L, Xu Y, Li W, Yang B, Yu S, Zhou H, Yang C, Xu F, Wang J, Gao Y, Huang Y, Lu L, Liang X. Diacylglycerol kinase (DGK) inhibitor II (R59949) could suppress retinal neovascularization and protect retinal astrocytes in an oxygen- induced retinopathy model. J Mol Neurosci. 2015 May;56(1):78-88. doi: 10.1007/s12031-014-0469-2. Epub 2014 Dec 2. PMID: 25451596. 8: Torres-Ayuso P, Daza-Martín M, Martín-Pérez J, Ávila-Flores A, Mérida I. Diacylglycerol kinase α promotes 3D cancer cell growth and limits drug sensitivity through functional interaction with Src. Oncotarget. 2014 Oct 30;5(20):9710-26. doi: 10.18632/oncotarget.2344. PMID: 25339152; PMCID: PMC4259432. 9: Massart J, Zierath JR, Chibalin AV. A simple and rapid method to characterize lipid fate in skeletal muscle. BMC Res Notes. 2014 Jun 24;7:391. doi: 10.1186/1756-0500-7-391. PMID: 24962347; PMCID: PMC4089939. 10: Kurohane Kaneko Y, Kobayashi Y, Motoki K, Nakata K, Miyagawa S, Yamamoto M, Hayashi D, Shirai Y, Sakane F, Ishikawa T. Depression of type I diacylglycerol kinases in pancreatic β-cells from male mice results in impaired insulin secretion. Endocrinology. 2013 Nov;154(11):4089-98. doi: 10.1210/en.2013-1356. Epub 2013 Sep 13. PMID: 24035999. 11: 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. 12: 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. 13: Kawaguchi M, Valencia JC, Namiki T, Suzuki T, Hearing VJ. Diacylglycerol kinase regulates tyrosinase expression and function in human melanocytes. J Invest Dermatol. 2012 Dec;132(12):2791-9. doi: 10.1038/jid.2012.261. Epub 2012 Aug 16. PMID: 22895365; PMCID: PMC3502659. 14: Nakano T, Hozumi Y, Goto K, Wakabayashi I. Involvement of diacylglycerol kinase γ in modulation of iNOS synthesis in Golgi apparatus of vascular endothelial cells. Naunyn Schmiedebergs Arch Pharmacol. 2012 Aug;385(8):787-95. doi: 10.1007/s00210-012-0760-0. Epub 2012 May 25. PMID: 22627682. 15: Marumo M, Nakano T, Takeda Y, Goto K, Wakabayashi I. Inhibition of thrombin- induced Ca²⁺ influx in platelets by R59949, an inhibitor of diacylglycerol kinase. J Pharm Pharmacol. 2012 Jun;64(6):855-61. doi: 10.1111/j.2042-7158.2012.01485.x. Epub 2012 Mar 12. PMID: 22571264. 16: Saadeh M, Ferrante TC, Kane A, Shirihai O, Corkey BE, Deeney JT. Reactive oxygen species stimulate insulin secretion in rat pancreatic islets: studies using mono-oleoyl-glycerol. PLoS One. 2012;7(1):e30200. doi: 10.1371/journal.pone.0030200. Epub 2012 Jan 17. PMID: 22272304; PMCID: PMC3260220. 17: Filigheddu N, Sampietro S, Chianale F, Porporato PE, Gaggianesi M, Gregnanin I, Rainero E, Ferrara M, Perego B, Riboni F, Baldanzi G, Graziani A, Surico N. Diacylglycerol kinase α mediates 17-β-estradiol-induced proliferation, motility, and anchorage-independent growth of Hec-1A endometrial cancer cell line through the G protein-coupled estrogen receptor GPR30. Cell Signal. 2011 Dec;23(12):1988-96. doi: 10.1016/j.cellsig.2011.07.009. Epub 2011 Jul 22. PMID: 21802511. 18: Baldanzi G, Pietronave S, Locarno D, Merlin S, Porporato P, Chianale F, Filigheddu N, Cantelmo AR, Albini A, Graziani A, Prat M. Diacylglycerol kinases are essential for hepatocyte growth factor-dependent proliferation and motility of Kaposi's sarcoma cells. Cancer Sci. 2011 Jul;102(7):1329-36. doi: 10.1111/j.1349-7006.2011.01953.x. Epub 2011 May 18. PMID: 21477072. 19: Shibata Y, Kawada-Matsuo M, Shirai Y, Saito N, Li D, Yamashita Y. Streptococcus mutans diacylglycerol kinase homologue: a potential target for anti-caries chemotherapy. J Med Microbiol. 2011 May;60(Pt 5):625-630. doi: 10.1099/jmm.0.026070-0. Epub 2011 Feb 11. PMID: 21317193. 20: Fuchs B, Rupp M, Ghofrani HA, Schermuly RT, Seeger W, Grimminger F, Gudermann T, Dietrich A, Weissmann N. Diacylglycerol regulates acute hypoxic pulmonary vasoconstriction via TRPC6. Respir Res. 2011 Feb 4;12(1):20. doi: 10.1186/1465-9921-12-20. PMID: 21294865; PMCID: PMC3042943.