R59949 is a pan-diacylglycerol kinase (DGK) inhibitor (antagonist) with IC50 of 300 nM. R59949 strongly inhibits the activity of type I DGKα and γ, and moderately weakens the activity of type II DGKθ and κ. R59949 activates protein kinase C (PKC) by increasing levels of the endogenous ligand diacylglycerol.

Physicochemical Properties

Molecular Formula	C28H25F2N3OS
Molecular Weight	489.58
Exact Mass	489.169
CAS #	120166-69-0
PubChem CID	657356
Appearance	White to off-white solid powder
Density	1.36g/cm3
Boiling Point	637.1ºC at 760mmHg
Flash Point	339.1ºC
Vapour Pressure	3.94E-16mmHg at 25°C
Index of Refraction	1.688
LogP	5.873
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	5
Heavy Atom Count	35
Complexity	770
Defined Atom Stereocenter Count	0
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)
Chemical Name	3-(2-(4-(bis(4-fluorophenyl)methylene)piperidin-1-yl)ethyl)-2-thioxo-2,3-dihydroquinazolin-4(1H)-one
Synonyms	R-59949 R59949 R 59949
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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.
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	Vasopressin- and collagen-induced release response and aggregation are markedly enhanced in the presence of R59949, which is linked to the production of arachidonic acid metabolites [1]. R59949 restricts the import of CCL2 in THP-1 monocytes. By decreasing the concentration of L-arginine solution across the plasma membrane in vascular smooth muscle cells, R59949 adsorbs the generation of inducible nitric oxide [4]. Half maximal concentration of the Ca2+ signal is 8.6 μM[2].
References	[1]. The role of endogenously formed diacylglycerol in the propagation and termination of platelet activation. A biochemical and functional analysis using the novel diacylglycerol kinase inhibitor, R 59 949. J Biol Chem. 1989;264(6):3274-3285. [2]. Inhibitors of DAG metabolism suppress CCR2 signalling in human monocytes. Br J Pharmacol. 2019;176(15):2736-2749. [3]. Effect of novel modulators of protein kinase C activity upon chemotherapy-induced differentiation and apoptosis in myeloid leukemic cells. Anticancer Drugs. 2002;13(7):725-733. [4]. 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;390(2):207-214.
Additional Infomation	3-[2-[4-[bis(4-fluorophenyl)methylidene]-1-piperidinyl]ethyl]-2-sulfanylidene-1H-quinazolin-4-one is a diarylmethane.

Solubility Data

Solubility (In Vitro)

DMSO : ~100 mg/mL (~204.26 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.11 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	2.0426 mL	10.2128 mL	20.4257 mL
	5 mM	0.4085 mL	2.0426 mL	4.0851 mL
	10 mM	0.2043 mL	1.0213 mL	2.0426 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.