| Size | Price | Stock | Qty |
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| Targets |
L-888607's primary and most well-supported target is the CRTH2 receptor, where it acts as a potent agonist. It has a very high affinity for the human CRTH2 receptor, with reported Ki values of 0.8 nM and 4 nM. It shows significantly lower affinity for other prostanoid receptors, including the DP1 receptor, TP receptor, EP2 receptor, EP4 receptor, and IP receptor. This high selectivity makes it a valuable tool for studying CRTH2-mediated signaling pathways.
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| ln Vitro |
L 888607, with a Ki value of 4 nM, exhibits strong affinity for the human CRTH2 receptor[1]. A certain affinity, with a Ki value of 211 nM, is exhibited by L 888607 for the human DP receptor(1). When it comes to CRTH2 receptors, L 888607 shows a comparatively strong selectivity[1]. A 0.4 nM EC50 value for L 888607 indicates that it has agonistic activity on both endogenously expressed and recombinant CRTH2 receptors[1]. The eosinophil chemotaxis is stimulated by L 888607 (100 nM, 20 minutes) [1].
In vitro, L-888607 demonstrates potent and selective agonism at the CRTH2 receptor. Its activity is characterized by its high binding affinity, with a Ki value of 0.8 nM. It effectively activates CRTH2-mediated signaling pathways, making it a useful probe for studying the receptor's function in various cell types, particularly those involved in the allergic and inflammatory response. |
| ln Vivo |
L-888607 (5 mg/kg intravenously as a single dose or 20 mg/kg orally as a single dose) has demonstrated a fair degree of stability in vivo [1].
In vivo, L-888607 has been reported to be orally active. Its pharmacokinetic profile has been studied in mice, where it has been administered both intravenously and orally. Due to its potent and selective CRTH2 agonism, it is a key compound for investigating the therapeutic potential of modulating the CRTH2 pathway in disease models. |
| Enzyme Assay |
The non-cellular assay for L-888607 primarily involves measuring its binding affinity for the CRTH2 receptor using radioligand binding assays. Membrane preparations from cells expressing the human CRTH2 receptor are incubated with a radiolabeled ligand and varying concentrations of L-888607. The inhibition of radioligand binding is measured, and the Ki value is determined from competition curves. This assay confirms its high affinity and selectivity for CRTH2 over other related receptors.
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| Cell Assay |
Immunofluorescence[1]
Cell Types: Human Eosinophils Tested Concentrations: 100 nM Incubation Duration: 20 minutes Experimental Results: Significant stimulation of eosinophil migration towards the bottom chamber. The cellular assay for L-888607 involves treating cells expressing the CRTH2 receptor and measuring its effects on receptor-mediated signaling. As an agonist, its activity can be assessed by measuring the mobilization of intracellular calcium or the inhibition of forskolin-stimulated cAMP accumulation. The EC50 for receptor activation is determined from concentration-response curves. These assays confirm its potent agonistic activity at the CRTH2 receptor. |
| Animal Protocol |
Animal/Disease Models: Male (ICR) BR mouse [1]
Doses: 5 mg/kg, 20 mg/kg Route of Administration: intravenous (iv) (iv)injection, 5 mg/kg, single dose or oral administration, 20 mg/kg, single dose Experimental Results: No obvious side effects were seen. In the in vivo efficacy study, L-888607 is typically administered orally to animal models of allergic inflammation or other diseases where the CRTH2 pathway is implicated. The compound's effects are assessed by measuring relevant biomarkers, such as inflammatory cell infiltration or cytokine levels. Its pharmacokinetic profile is also evaluated to determine its absorption, distribution, metabolism, and excretion. |
| ADME/Pharmacokinetics |
L-888607 has a molecular weight of 375.84 g/mol and a molecular formula of C19H15ClFNO2S. The compound is soluble in DMSO. It should be stored as a powder at -20°C for up to 3 years or in solvent at -80°C for up to 1 year. L-888607 is noted to be stable and orally active.
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| Toxicity/Toxicokinetics |
The toxicological profile of L-888607 has not been extensively characterized in the published literature. As a potent CRTH2 agonist, its effects would be primarily related to the modulation of the CRTH2 pathway. Comprehensive toxicology data are limited, and the compound is not approved for clinical use. It should be handled with appropriate laboratory safety precautions.
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| References | |
| Additional Infomation |
L-888607 is a potent and selective CRTH2 agonist that serves as a key research tool for studying the role of the CRTH2 receptor in allergic and inflammatory diseases. Its primary application is in target validation and pathway elucidation, rather than as a therapeutic candidate. It is important to note that its mechanism of action is clearly defined as CRTH2 agonism, differentiating it from the previously described, inaccurate profile. L-888607 is not approved for clinical use and is strictly a research compound.
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| Molecular Formula |
C19H15CLFNO2S
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|---|---|
| Molecular Weight |
375.844306230545
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| Exact Mass |
375.049
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| CAS # |
860033-06-3
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| Related CAS # |
L 888607 Racemate;1030017-51-6;(R)-L 888607;2446042-90-4
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| PubChem CID |
44403763
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
583.8±50.0 °C at 760 mmHg
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| Flash Point |
306.9±30.1 °C
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| Vapour Pressure |
0.0±1.7 mmHg at 25°C
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| Index of Refraction |
1.689
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| LogP |
4.4
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
25
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| Complexity |
502
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C1(=CC=C2C(=C1)N1CC[C@@H](CC(=O)O)C1=C2SC1=CC=C(Cl)C=C1)F
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| InChi Key |
GSBAVONRPNJJOH-NSHDSACASA-N
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| InChi Code |
InChI=1S/C19H15ClFNO2S/c20-12-1-4-14(5-2-12)25-19-15-6-3-13(21)10-16(15)22-8-7-11(18(19)22)9-17(23)24/h1-6,10-11H,7-9H2,(H,23,24)/t11-/m0/s1
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| Chemical Name |
2-[(3S)-4-(4-chlorophenyl)sulfanyl-7-fluoro-2,3-dihydro-1H-pyrrolo[1,2-a]indol-3-yl]acetic acid
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| Synonyms |
L 888,607; L888,607; L-888,607
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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 : ≥ 150 mg/mL (~399.11 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.65 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 (6.65 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 | 2.6607 mL | 13.3035 mL | 26.6071 mL | |
| 5 mM | 0.5321 mL | 2.6607 mL | 5.3214 mL | |
| 10 mM | 0.2661 mL | 1.3304 mL | 2.6607 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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