| Size | Price | Stock | Qty |
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| 5mg |
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| Targets |
FKGK18 targets group VIA calcium-independent phospholipase A2 (GVIA iPLA2 or iPLA2β), an enzyme involved in phospholipid metabolism and cell signaling. It inhibits GVIA iPLA2 by 99.9% at 0.091 mole fraction in a mixed micelle activity assay. FKGK18 has IC50s of 50 nM for iPLA2β and 3 μM for iPLA2γ, and is selective over GIVA cPLA2 and GV sPLA2.
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| ln Vitro |
Prostaglandin E2 (PGE2) and glucose-stimulated insulin secretion (GSIS) are inhibited by FKGK18 (1 nM; 1 h) [2]. A 24 hour dose of FKGK18 (0.1–10 nM) reduces β-cell apoptosis [3]. B cell survival and immune cell function are impacted by FKGK18 (0.1–10 μM; 24 hours) [3].
In vitro, FKGK18 potently inhibits GVIA iPLA2 with an IC50 of 50 nM for iPLA2β and 3 μM for iPLA2γ. It inhibits GVIA iPLA2 by 99.9% at 0.091 mole fraction in a mixed micelle activity assay. The compound shows selectivity for GVIA iPLA2 over GIVA cPLA2 (80.8% inhibition) and GV sPLA2 (36.8% inhibition). |
| ln Vivo |
Diabetes incidence is lowered by FKGK18 (20 mg/kg; intraperitoneally administered three times a week, beginning on day 10 and continuing until death) [3].
In vivo, FKGK18 (20 mg/kg, 3 times per week) reduces blood glucose levels in an intraperitoneal glucose tolerance test, decreases the incidence of diabetes, and increases serum insulin levels in non-obese diabetic (NOD) mice. These effects suggest that iPLA2β inhibition may have therapeutic potential for diabetes. |
| Enzyme Assay |
The in vitro enzyme activity assay for FKGK18 involves measuring its inhibitory effect on group VIA calcium-independent phospholipase A2 (GVIA iPLA2) activity. The enzyme is incubated with varying concentrations of FKGK18 and a phospholipid substrate in a mixed micelle assay. Enzymatic activity is measured by monitoring the release of free fatty acids or using radiolabeled substrates. FKGK18 inhibits GVIA iPLA2 by 99.9% at 0.091 mole fraction with IC50s of 50 nM and 3 μM for iPLA2β and iPLA2γ.
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| Cell Assay |
Cell viability assay [2]
Cell Types: human islet Tested Concentrations: 1 nM Incubation Duration: 1 hour Experimental Results: Inhibition of GSIS of islets, AA hydrolysis of β-cell membrane and PGE2 production. Penetrated islets and beta cells from islets. Apoptosis analysis [2] Cell Types: INS-1 OE Cell Tested Concentrations: 0.1-10 nM Incubation Duration: 24 hrs (hours) Experimental Results: Inhibition of ER stress-induced β-cell apoptosis. Cell viability assay[3] Cell Types: CD4+ T cells and B cells from 8-12 week old NOD female mice Tested Concentrations: 0.1-10 μM/L Incubation Duration: 24 hrs (hours) Experimental Results: diminished TNF-α production, diminished B cells activity and antibody production. In vitro cellular assays for FKGK18 involve treating cultured cells with varying concentrations of the compound. iPLA2 activity in cell lysates is measured using fluorogenic or radiolabeled phospholipid substrates. Cellular phospholipid metabolism and signaling pathways are assessed. The compound's selectivity for iPLA2β over other phospholipase isoforms is confirmed using isoform-specific assays. |
| Animal Protocol |
Animal/Disease Models: 10-day-old female NOD mice [3]
Doses: 20 mg/kg Route of Administration: intraperitoneal (ip) injection; 20 mg/kg, 3 times a week; from 10 days to euthanasia Experimental Results: Reduce the incidence of diabetes and maintain better health Good glucose homeostasis. In vivo animal experiments for FKGK18 use non-obese diabetic (NOD) mice, a model of autoimmune diabetes. FKGK18 is administered at 20 mg/kg, 3 times per week. Intraperitoneal glucose tolerance tests are performed to assess glucose metabolism. Blood glucose and serum insulin levels are measured. The incidence of diabetes is monitored. FKGK18 reduces blood glucose levels, decreases diabetes incidence, and increases serum insulin levels. |
| ADME/Pharmacokinetics |
Pharmacokinetic (PK) properties of FKGK18 have not been extensively characterized in publicly available literature. The compound is a fluoroketone-based iPLA2 inhibitor with molecular weight of 320.32 (C16H13F3O2). As a small molecule, it is expected to be administered via intraperitoneal or oral routes. Specific PK parameters including half-life, bioavailability, and metabolic pathways are not well documented.
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| Toxicity/Toxicokinetics |
Toxicological (toxicology) data for FKGK18 are limited in publicly available sources. The compound has been studied in NOD mice at a dose of 20 mg/kg, 3 times per week, suggesting tolerability at this dose. However, systematic toxicology studies including acute, repeated-dose, and genotoxicity assessments have not been well documented. Standard safety pharmacology studies would be required for therapeutic development.
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| References |
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| Additional Infomation |
Inhibits Ca(II)-independent phospholipase A2 in group VIA; structure can be found in the first reference.
FKGK18 (CAS#: 1071001-09-6) is a selective inhibitor of group VIA calcium-independent phospholipase A2 (GVIA iPLA2 or iPLA2β). It has IC50s of 50 nM and 3 μM for iPLA2β and iPLA2γ, and shows selectivity over other phospholipase isoforms. In NOD mice, FKGK18 reduces blood glucose, decreases diabetes incidence, and increases serum insulin levels. FKGK18 is not approved for clinical use and remains a research compound. |
| Molecular Formula |
C16H15F3O
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| Molecular Weight |
280.2902
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| Exact Mass |
280.107
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| CAS # |
1071001-09-6
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| PubChem CID |
25060069
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
382.5±42.0 °C at 760 mmHg
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| Flash Point |
202.8±19.4 °C
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| Vapour Pressure |
0.0±0.9 mmHg at 25°C
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| Index of Refraction |
1.528
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| LogP |
4.8
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
20
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| Complexity |
324
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC=C2C=C(C=CC2=C1)CCCCC(=O)C(F)(F)F
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| InChi Key |
VCWWTQMRNJSJGC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H15F3O/c17-16(18,19)15(20)8-4-1-5-12-9-10-13-6-2-3-7-14(13)11-12/h2-3,6-7,9-11H,1,4-5,8H2
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| Chemical Name |
1,1,1-trifluoro-6-naphthalen-2-ylhexan-2-one
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| Synonyms |
FKGK 18; FKGK-18; FKGK18
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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 : ~50 mg/mL (~178.39 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.25 mg/mL (4.46 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 12.5 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: ≥ 1.25 mg/mL (4.46 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 12.5 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. View More
Solubility in Formulation 3: ≥ 1.25 mg/mL (4.46 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.5677 mL | 17.8387 mL | 35.6773 mL | |
| 5 mM | 0.7135 mL | 3.5677 mL | 7.1355 mL | |
| 10 mM | 0.3568 mL | 1.7839 mL | 3.5677 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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