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| Targets |
(R)-L 888607 exhibits no measurable affinity for the human CRTH2 receptor, in stark contrast to the active (S)-enantiomer L-888607 which binds with subnanomolar affinity (Ki = 0.8-4 nM) and acts as a potent and selective synthetic agonist. The racemate (L 888607 Racemate) shows modest binding affinity for DP1 (prostaglandin D2 receptor subtype 1, Ki = 132 nM) and thromboxane A2 receptor (TP, Ki = 17 nM). However, the (R)-isomer is designed to be completely inert at CRTH2, eliminating confounding agonism in controlled experiments.
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| ln Vitro |
In vitro, (R)-L 888607 shows no agonist activity at the CRTH2 receptor in functional assays such as [35S]GTPgammaS binding, calcium flux, or eosinophil shape change assays. Its complete lack of activity makes it an ideal negative control for distinguishing CRTH2-specific effects from non-specific scaffold effects. When substituted for the racemate or active enantiomer, CRTH2 pathway investigations become uninterpretable because the active stereoisomer produces confounding agonism. The (R)-isomer allows definitive attribution of observed effects to CRTH2 agonism by the test compound.
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| ln Vivo |
In vivo, (R)-L 888607 provides an inactive comparator for controlling non-CRTH2 scaffold effects in animal models. It is used in pharmacological studies as a matched inactive control to ensure that observed effects in response to CRTH2 agonists or antagonists are truly mediated through CRTH2 receptor engagement rather than off-target interactions. The (R)-isomer is administered via intravenous (i.v.) or oral (p.o.) routes at doses matched to the active enantiomer, and the absence of CRTH2-mediated responses confirms specificity.
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| Enzyme Assay |
Cell-free receptor binding protocol for CRTH2: Membrane preparations from CHO cells expressing human recombinant CRTH2 are incubated with varying concentrations of test compound (including (R)-L 888607 as a negative control) and [3H]-PGD2 or other radiolabeled ligand in binding buffer at 25degC for 60-120 minutes. Bound and free radioligand are separated by filtration through GF/B filters presoaked in 0.3% polyethyleneimine. Radioactivity is counted by scintillation, and Ki values are calculated using Cheng-Prusoff equation. (R)-L 888607 shows no measurable displacement in this assay.
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| Cell Assay |
Cell-based functional assay protocol for CRTH2 agonism: CHO-K1 cells stably expressing human CRTH2 are seeded in 96-well plates. Cells are loaded with calcium-sensitive dye (e.g., Fluo-4) and treated with (R)-L 888607 or active L-888607 (0.01-1000 nM) using a fluorescence plate reader. Calcium flux is measured as change in fluorescence over time. For [35S]GTPgammaS binding assays, cell membranes are incubated with GDP, [35S]GTPgammaS, and test compounds, and bound radioactivity is counted. (R)-L 888607 produces no significant signal in these assays.
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| Animal Protocol |
In vivo animal protocol for CRTH2 pharmacological studies: Mice (C57BL/6 or CRTH2 knockout mice for specificity controls) are administered (R)-L 888607 via intravenous (i.v.) injection or oral (p.o.) gavage at matched doses (e.g., 0.1-10 mg/kg) as a negative control alongside the active (S)-enantiomer or other CRTH2 agonists. Pharmacodynamic endpoints may include eosinophil shape change, plasma cytokine levels (IL-4, IL-5, IL-13), or airway hyperresponsiveness in asthma models. (R)-L 888607-treated animals should show no response compared to vehicle.
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| ADME/Pharmacokinetics |
Limited pharmacokinetic data are available for the racemate L 888607. The active (S)-enantiomer L-888607 is orally bioavailable and shows relative stability in vivo, with pharmacokinetic profile characterized over 8 hours following intravenous or oral administration in mice. The (R)-isomer likely exhibits similar absorption and distribution properties, though it is used exclusively as a control and not for therapeutic or PK-focused studies. Its primary value is in controlled experiments rather than PK characterization.
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| Toxicity/Toxicokinetics |
No toxicity studies have been conducted on (R)-L 888607, as it is an experimental control compound for in vitro and in vivo pharmacological research and is not intended for therapeutic use. It is used at low concentrations in receptor binding and functional assays. Standard laboratory safety precautions for handling organic compounds are recommended. The compound should be stored as supplied at -20degC and protected from light and moisture.
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| References |
[1]. Gervais FG, Identification of a potent and selective synthetic agonist at the CRTH2 receptor. Mol Pharmacol. 2005 Jun;67(6):1834-9.
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| Additional Infomation |
(R)-L 888607 is not a drug and has no clinical applications or regulatory approval. It is a research-grade compound used exclusively as an inactive negative control for CRTH2 receptor pharmacology studies. The active (S)-enantiomer L-888607 is a potent and selective synthetic agonist at CRTH2 with applications in studying Th2-mediated inflammatory conditions including asthma, atopic dermatitis, and allergic rhinitis. (R)-L 888607 serves as an essential stereochemically matched control to validate the specificity of CRTH2-mediated effects in both in vitro and in vivo experiments, ensuring that observed activities are attributable to target engagement rather than non-specific interactions.
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| Molecular Formula |
C19H15CLFNO2S
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|---|---|
| Molecular Weight |
375.84
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| Exact Mass |
375.049
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| CAS # |
2446042-90-4
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| Related CAS # |
L 888607;860033-06-3;L 888607 Racemate;1030017-51-6
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| PubChem CID |
86312208
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| Appearance |
Light yellow to yellow solid powder
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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 |
C1CN2C3=C(C=CC(=C3)F)C(=C2[C@H]1CC(=O)O)SC4=CC=C(C=C4)Cl
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| InChi Key |
GSBAVONRPNJJOH-LLVKDONJSA-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-/m1/s1
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| Chemical Name |
2-[(3R)-4-(4-chlorophenyl)sulfanyl-7-fluoro-2,3-dihydro-1H-pyrrolo[1,2-a]indol-3-yl]acetic acid
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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 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)
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| Solubility (In Vitro) |
DMSO: ≥ 100 mg/mL (266.07 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (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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