| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| Other Sizes |
| Targets |
PKC serotonin DGK 2.8 μM (IC50)
The primary targets of R 59-022 hydrochloride include diacylglycerol kinase (DGK), protein kinase C (PKC), and 5-HT2 receptors. It potently inhibits DGK with an IC50 of about 20 μM. It also inhibits PKC at higher concentrations and acts as a 5-HT2 antagonist. By inhibiting DGK, it increases cellular levels of diacylglycerol, thereby modulating PKC activity and other downstream signaling pathways. |
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| ln Vitro |
R59-022 (10 μM, 1 min) hydrochloride increases aggregation of platelets [2]. Norepinephrine release from chromaffin cells is enhanced by R 59-022 (30 μM, 0-60 min) hydrochloride [3]. PKC is activated in HeLa and U87 cells by R 59-022 hydrochloride (40 μM, 30 minutes) [4]. The entry of EBOV GP into Vero cells is blocked by R 59-022 (0-10 μM, 4 hours) hydrochloride [5].
In vitro, R 59-022 hydrochloride potently inhibits diacylglycerol kinase with an IC50 of about 20 μM. It also inhibits protein kinase C (PKC) at higher concentrations. The compound is a 5-HT2 antagonist. It is used to study the role of DGK in various cellular processes, including cell proliferation, differentiation, and apoptosis. The compound has been shown to enhance PKC activation by increasing DAG levels. |
| ln Vivo |
SCID mice transplanted with U87 GBM cells had a considerably higher median survival rate when given 59-022 (2 mg/kg, i.p., for 12 days) hydrochloride [6].
In vivo activity of R 59-022 hydrochloride has been studied in animal models, but detailed data are limited. It has been used to investigate the involvement of DGK in platelet aggregation and other physiological processes. The compound may exhibit central nervous system effects due to its 5-HT2 antagonism. However, comprehensive pharmacokinetic and pharmacodynamic studies are not widely available. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays for R 59-022 hydrochloride typically involve DGK activity assays. The enzyme is incubated with varying concentrations of the compound (0.1-100 µM) in the presence of a substrate (e.g., [3H]-DAG). DGK activity is measured by quantifying the conversion of DAG to phosphatidic acid. PKC inhibition is assessed using standard kinase activity assays. 5-HT2 receptor binding is measured using radioligand displacement assays.
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| Cell Assay |
Western Blot Analysis[4]
Cell Types: HeLa cells Tested Concentrations: 40 uM Incubation Duration: 30 min Experimental Results: Increased the phosphorylation of PKC downstream targets by about 2.5-fold. In vitro cellular assays for R 59-022 hydrochloride involve testing its effects on DGK activity and downstream signaling. Cells are treated with varying concentrations of the compound (1-50 µM) for various time points. DAG levels are measured by lipid extraction and HPLC. PKC activity is assessed by measuring phosphorylation of specific substrates. The compound demonstrates concentration-dependent inhibition of DGK and modulation of DAG-dependent signaling. |
| 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: Increased median survival and diminished tumor volume. In vivo animal studies for R 59-022 hydrochloride have been conducted primarily in models of platelet aggregation and central nervous system function. Animals are treated with the compound via intravenous or intraperitoneal administration. Platelet aggregation is measured in vitro after ex vivo treatment. Behavioral effects related to 5-HT2 antagonism may be assessed in rodent models. However, detailed protocols are not well standardized. |
| ADME/Pharmacokinetics |
R 59-022 hydrochloride has a molecular formula of C28H28ClN3O•HCl and a molecular weight of 490.47. It appears as a solid powder with a purity of ≥98%. It is soluble in DMSO and ethanol. The compound should be stored at -20°C, protected from light, and is stable for up to 1 year when stored as a dry powder. Stock solutions should be prepared fresh and stored at -20°C for short-term use. It is intended for research use only and is not for human consumption.
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| Toxicity/Toxicokinetics |
The toxicity profile of R 59-022 hydrochloride has not been extensively characterized. As a DGK inhibitor and 5-HT2 antagonist, it may have central and peripheral effects. Standard toxicity studies would include assessment of acute oral toxicity, repeated-dose toxicity, and genotoxicity in animal models. The compound is intended for research use only and is not approved for clinical use.
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| References |
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| Additional Infomation |
R 59-022 hydrochloride (CAS 93076-98-3) is a potent inhibitor of diacylglycerol kinase (DGK) with an IC50 of about 20 μM. It also inhibits PKC at higher concentrations and acts as a 5-HT2 antagonist. It has a molecular formula of C28H28ClN3O•HCl and a molecular weight of 490.47. The compound is used in research to study lipid signaling, platelet aggregation, and central nervous system function. It is intended for research use only and is not approved for clinical use.
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| Molecular Formula |
C27H27CLFN3OS
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|---|---|
| Molecular Weight |
496.039187669754
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| Exact Mass |
495.154
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| CAS # |
93076-98-3
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| Related CAS # |
R 59-022;93076-89-2
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| PubChem CID |
23326062
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| Appearance |
Off-white to light yellow solid powder
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
34
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| Complexity |
868
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C(C1C=CC=CC=1)(C1C=CC(F)=CC=1)=C1CCN(CCC2=C(N=C3SC=CN3C2=O)C)CC1.Cl
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| InChi Key |
APNKGVNEUKASGR-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C27H26FN3OS.ClH/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;1H
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| Chemical Name |
6-[2-[4-[(4-fluorophenyl)-phenylmethylidene]piperidin-1-yl]ethyl]-7-methyl-[1,3]thiazolo[3,2-a]pyrimidin-5-one;hydrochloride
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO : 25 mg/mL (50.40 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.04 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 (5.04 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 saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. View More
Solubility in Formulation 3: 2.5 mg/mL (5.04 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0160 mL | 10.0798 mL | 20.1597 mL | |
| 5 mM | 0.4032 mL | 2.0160 mL | 4.0319 mL | |
| 10 mM | 0.2016 mL | 1.0080 mL | 2.0160 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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