| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg | |||
| Other Sizes |
| Targets |
IC50: 32 nM (LPA5)[1]
LPA5 antagonist 1 targets the lysophosphatidic acid receptor 5 (LPA5, also known as LPAR5 or GPR92), a G protein-coupled receptor (GPCR) that is activated by the bioactive lipid lysophosphatidic acid (LPA). LPA5 is involved in several pathological processes, including pain transmission, neuropathic pain, cancer, and fibrosis. By blocking LPA5 with this antagonist (IC50 = 32 nM), the compound reduces LPA-mediated signaling, which contributes to its anti-nociceptive (pain-reducing) effects. It can be used in inflammatory and neuropathic pain research. |
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| ln Vitro |
hLPA5 calcium mobilization is inhibited by LPA5 antagonist 2 (0-10 μM), with an IC50 value of 32 nM[1]. Good target selectivity for LPA5 is demonstrated by LPA5 antagonist 2 (0-10 μM)[1].
In vitro, LPA5 antagonist 1 (Compound 66) potently and selectively inhibits human LPA5-mediated calcium mobilization with an IC50 of 32 nM. It shows high selectivity for LPA5 over other LPA receptors (LPA1-4) and other GPCRs. The compound is used to study the role of LPA5 in LPA-induced signaling, such as calcium flux, cAMP modulation, and cell migration. It is a click chemistry reagent, containing an Alkyne group that can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups. This feature allows it to be used in chemical biology experiments, such as target engagement studies and the creation of fluorescent probes. |
| ln Vivo |
In vivo brain exposure is demonstrated by LPA5 antagonist 1 therapy (17.8 mg/kg; once intraperitoneal injection)[1]. In an inflammatory pain paradigm, administration of LPA5 antagonist 1 (intraperitoneal injection; 5.6, 10, and 17.8 mg/kg; once) decreases mechanical allodynia[1].
In vivo, LPA5 antagonist 1 shows high brain permeability and anti-nociceptive activity. This makes it suitable for studying pain pathways in the central nervous system. It can be used in animal models of inflammatory pain (e.g., complete Freund's adjuvant (CFA)-induced pain, carrageenan-induced paw edema) and neuropathic pain (e.g., chronic constriction injury (CCI) of the sciatic nerve, streptozotocin-induced diabetic neuropathy). By blocking LPA5, the compound reduces pain behaviors, such as mechanical allodynia and thermal hyperalgesia. It can be used for the research of inflammatory and neuropathic pain. |
| Enzyme Assay |
An in vitro biochemical assay for LPA5 is a calcium mobilization assay using cells that express human LPA5. CHO-K1 or HEK293 cells stably expressing human LPA5 are seeded in a 96-well plate. They are loaded with a calcium-sensitive fluorescent dye (e.g., Fluo-4 or Cal-520). Varying concentrations of LPA5 antagonist 1 (0-10 microM) are added to the cells, followed by the addition of a submaximal concentration of LPA (e.g., 100 nM) to activate the receptor. The change in fluorescence is measured by a fluorometric imaging plate reader (FLIPR). The half-maximal inhibitory concentration (IC50) is calculated from the dose-response curve. Reported IC50 = 32 nM. This assay is used to assess the antagonist activity.
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| Cell Assay |
A cellular assay for LPA5 antagonist 1 is a cell migration assay using cancer cell lines that express LPA5 (e.g., certain breast cancer or pancreatic cancer cell lines). Cells are seeded in the upper chamber of a transwell migration plate (8-microm pore size). Serum-free media containing LPA (0.1-1 microM) is placed in the lower chamber as a chemoattractant. The test compound (LPA5 antagonist 1) is added to both chambers at varying concentrations (0-10 microM). After 16-24 hours of incubation, the number of migrated cells (attached to the lower side of the filter) is quantified by staining (e.g., crystal violet) and counting under a microscope or by fluorescence measurement. Alternatively, an invasion assay through Matrigel-coated filters can be performed. The compound reduces LPA-stimulated migration.
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| Animal Protocol |
Animal/Disease Models: CFA-induced inflammatory pain model in SD (Sprague-Dawley) rats[1]
Doses: 5.6, 10, and 17.8 mg/kg Route of Administration: intraperitoneal (ip) injection; 5.6, 10, and 17.8 mg/kg; once Experimental Results: decreased mechanical allodynia in a dose-dependent manner. Animal/Disease Models: Male SD (Sprague-Dawley) rats[1] Doses: 17.8 mg/kg Route of Administration: intraperitoneal (ip) injection; 17.8 mg/kg; once Experimental Results: demonstrated brain concentrations of 652 ng/mL , after treatment 30 minutes. In vivo studies for LPA5 antagonist 1 can be performed in a mouse model of neuropathic pain, such as the chronic constriction injury (CCI) model. Adult male C57BL/6 mice undergo surgery to expose the sciatic nerve, and four loose ligatures are placed around the nerve to induce neuropathic pain. Starting 7 days after surgery (when pain behavior is established), mice are treated with LPA5 antagonist 1 at doses of 1-30 mg/kg via intraperitoneal (IP) injection or oral gavage, once or twice daily for 5-7 days. Pain behaviors are assessed before and at various times after treatment: mechanical allodynia is measured using von Frey filaments, and thermal hyperalgesia is measured using a Hargreaves plantar test. At the end of the study, spinal cord and brain tissues are collected for analysis of LPA5 expression, glial markers (Iba-1, GFAP), and inflammatory cytokines (IL-1beta, IL-6, TNF-alpha) by qPCR and immunohistochemistry. |
| ADME/Pharmacokinetics |
LPA5 antagonist 1 has a molecular weight of 486.58 and a molecular formula of C28H26N2O4S. It is a solid powder with a purity of ≥98%. It is soluble in DMSO (100 mg/mL). For in vivo use, it can be formulated in vehicles such as 10% DMSO, 40% PEG300, 5% Tween-80, and 45% saline, or 10% DMSO, 90% corn oil, to achieve a clear solution at 2.5 mg/mL. The compound shows high brain permeability, indicating good penetration of the blood-brain barrier. The specific pharmacokinetic parameters (half-life, bioavailability, Cmax, AUC) have not been reported but are likely favorable for CNS-targeted studies.
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| Toxicity/Toxicokinetics |
Specific toxicity data for LPA5 antagonist 1 is not available. As a potent and selective LPA5 antagonist, on-target toxicity is expected to be limited due to the specific role of LPA5 in pain signaling. The compound has been reported to show high brain permeability and anti-nociceptive activity without apparent adverse effects in animal studies at the doses tested. Standard safety precautions for handling small molecule inhibitors should be followed, including the use of personal protective equipment (gloves, lab coat, safety goggles) and working in a well-ventilated area. The compound is not for human use.
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| References |
[1]. Zhang DH, et al. Isoquinolone derivatives as lysophosphatidic acid receptor 5 (LPA5) antagonists: Investigation of structure-activity relationships, ADME properties and analgesic effects. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. Volume 243, 5 December 2022, 114741.
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| Additional Infomation |
LPA5 antagonist 1 (Compound 66; CAS 2839471-45-1) is a potent and selective antagonist of lysophosphatidic acid receptor 5 (LPA5), a member of the GPCR family. LPA5 is expressed in the brain (particularly in the cortex, hippocampus, and thalamus) and in sensory neurons. It is involved in the regulation of pain, neuroinflammation, and cancer progression. By blocking LPA5, the compound shows high brain permeability and anti-nociceptive activity, making it a valuable tool for studying inflammatory and neuropathic pain. The compound also contains an alkyne group, making it a click chemistry reagent for bioconjugation and target identification studies. It is strictly a research chemical and is not approved for any clinical indication.
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| Exact Mass |
486.161
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|---|---|
| CAS # |
2839471-45-1
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| PubChem CID |
165412765
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| Appearance |
Off-white to light yellow solid powder
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
35
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| Complexity |
904
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=CSC2=C1C=C(C=C2)N3C=C(C4=CC(=C(C=C4C3=O)OC)OC)C(=O)N5CCC(CC5)C#C
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| InChi Key |
KNTSYYKDKFNRKN-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C28H26N2O4S/c1-5-18-8-10-29(11-9-18)27(31)23-15-30(19-6-7-26-20(12-19)17(2)16-35-26)28(32)22-14-25(34-4)24(33-3)13-21(22)23/h1,6-7,12-16,18H,8-11H2,2-4H3
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| Chemical Name |
4-(4-ethynylpiperidine-1-carbonyl)-6,7-dimethoxy-2-(3-methyl-1-benzothiophen-5-yl)isoquinolin-1-one
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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.) |
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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