| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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Lu AF27139 a novel rodent-active and CNS-penetrant P2X7 receptor antagonist, which is highly selective and potent against rat, mouse, and human forms of the receptors.
| ln Vitro |
Lu AF27139 (compound 1) (10-200 nM) exhibits dose-responsive inhibition of 100 μM BzATP-induced currents in HEK293 cells transfected with rat P2X7R, with an IC50 of 66 nM [1]. In primary rat microglia, Lu AF27139 (compound 1) (100 nM) inhibits 300 μM BzATP-induced currents with an 80% inhibition rate at 100 nM dose [1]. Lu AF27139 (compound 1) has an IC50 of 38 ± 2.5 nM, which inhibits the release of IL-1β from THP-1 cells when they are primed with LPS and when BzATP is added [1]. Compound 1, Lu AF27139, has an IC50 of 38 ± 38 in rats and inhibits the release of IL-1β in primary cortical microglia of mice and rats that have been primed with LPS and stimulated with 1 mM BzATP in a concentration-dependent manner. 19 nM, and in mice, its IC50 was 26 ± 6 nM[1].
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| ln Vivo |
Compound 1, Lu AF27139, when taken orally at doses of 3, 10, and 100 mg/kg, decreases the release of IL-1β in the frontal cortex of rats and mice when LPS is administered intracerebroventricularly (icv) and when BzATP is triggered [1]. Assessing the pharmacokinetic (PK) properties of compound 1 (Lu AF27139) in rats [1]. Dose Cu, plasma (nM)a Cu, brain (nM)a Cu, spinal cord (nM)a (mg/kg, po) (1 h) (2 h) (1 h) (2 h) (1 h) 2 h) T1 22.4 ± 4.2 22.8 ± 10 5.4 ± 2.6 6.4 ± 2.0 5.20 ± 0.80 10.0 ± 2.0 a: The concentrations of Lu AF27139 in rats' free plasma, brain, and spinal cord were calculated using the formula (Ct*fu), where Ct is the total tissue (plasma, brain, or spinal cord) drug concentration, and fu is the unbound fraction of these tissues ascertained by ex vivo equilibrium dialysis. The values from n = 3 animals are expressed as mean ± SEM. Fu = 0.02 ± 0.00 for plasma, 0.07 ± 0.03 for spinal cord, and 0.09 ± 0.03 for brain. The results for experiments with n ≥ 3 are presented as mean ± SEM.
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| Animal Protocol |
Animal/Disease Models: Male SD (SD (Sprague-Dawley)) rat (280-350 g); Male C57BL mouse (18-25g) [1]
Doses: 3, 10 and 100 mg/kg Route of Administration: Oral Experimental Results: Rat frontal cortex LPS-triggered and BzATP-triggered intracerebroventricular (icv) release were diminished in mice. |
| References |
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| Molecular Formula |
C21H19CLF3N5O2S
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|---|---|
| Molecular Weight |
497.9211
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| Exact Mass |
497.09
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| Elemental Analysis |
C, 50.66; H, 3.85; Cl, 7.12; F, 11.45; N, 14.07; O, 6.43; S, 6.44
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| CAS # |
2097117-06-9
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| PubChem CID |
129099048
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| Appearance |
White to off-white solid powder
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| LogP |
3.3
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
33
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| Complexity |
644
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C1COCCN1[C@H](CNC(=O)C2=C(N=C(S2)C3=NC=CC=N3)C(F)(F)F)C4=CC=C(C=C4)Cl
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| InChi Key |
FGPQIEDRTXLBES-OAHLLOKOSA-N
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| InChi Code |
InChI=1S/C21H19ClF3N5O2S/c22-14-4-2-13(3-5-14)15(30-8-10-32-11-9-30)12-28-19(31)16-17(21(23,24)25)29-20(33-16)18-26-6-1-7-27-18/h1-7,15H,8-12H2,(H,28,31)/t15-/m1/s1
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| Chemical Name |
(S)-N-(2-(4-chlorophenyl)-2-morpholinoethyl)-2-(pyrimidin-2-yl)-4-(trifluoromethyl)thiazole-5-carboxamide
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| Synonyms |
Lu AF-27139Lu AF27139 Lu AF 27139LuAF-27139 LuAF27139 LuAF 27139
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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 : ~125 mg/mL (~251.04 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.18 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 20.8 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: ≥ 2.08 mg/mL (4.18 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 20.8 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: ≥ 2.08 mg/mL (4.18 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 | 2.0084 mL | 10.0418 mL | 20.0835 mL | |
| 5 mM | 0.4017 mL | 2.0084 mL | 4.0167 mL | |
| 10 mM | 0.2008 mL | 1.0042 mL | 2.0084 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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