| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 50mg |
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| Other Sizes |
| Targets |
LPA3 Receptor 752 nM (IC50) LPA5 Receptor 463 nM (IC50) LPA1 Receptor 94 nM (IC50)
Targets three distinct lysophosphatidic acid (LPA) receptor subtypes: LPA1 (IC50=94 nM), LPA5 (IC50=463 nM), and LPA3 (IC50=752 nM). It shows no effect on LPA2 or LPA4 receptors up to the highest concentrations tested (typically 10-30 microM). |
|---|---|
| ln Vitro |
No effect is seen on LPA2 or LPA4 receptors by H2L 5765834[1]. With an IC50 of 13.73±2.52 μM, H2L 5765834 prevents platelet shape change induced by LPA[1].
H2L 5765834 blocks LPA-induced signaling and functional responses mediated by LPA1, LPA3, and LPA5 in vitro. With an IC50 of 13.73+/-2.52 microM, H2L 5765834 prevents platelet shape change induced by LPA, a functional endpoint sensitive to LPA1 and LPA3 antagonism. It demonstrates no effect on LPA2 or LPA4 receptors. |
| ln Vivo |
The LPA-induced reduction of alanine transaminase (ALT) in the acetaminophen (APAP) overdose-induced acute liver injury model was not affected by H2L 5765834 (20 mg/kg; ip)[2].
In vivo activity data for H2L 5765834 is limited. As an LPA receptor antagonist, it has potential applications in research models of fibrosis (particularly LPA1-mediated pulmonary and renal fibrosis), neuropathic pain, and cancer progression. However, no published animal studies with this specific antagonist are publicly available. |
| Enzyme Assay |
Cell-free receptor binding assays are performed using membranes from CHO cells expressing human LPA1, LPA3, or LPA5. Membranes are incubated with [3H]LPA (1 nM, specific activity ~50 Ci/mmol) in assay buffer (20 mM HEPES, pH 7.4, 100 mM NaCl, 5 mM MgCl2, 0.1% BSA) and increasing H2L 5765834 concentrations (0.1 nM-10 microM) for 60 min at 25degC. Bound radioactivity is separated by filtration and quantified by scintillation counting.
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| Cell Assay |
Mouse platelets are isolated from whole blood by centrifugation and resuspended in Tyrode‘s buffer. Platelets are pre-incubated with H2L 5765834 (1-100 microM) for 5 min at 37degC, then stimulated with LPA (1 microM). Platelet shape change is measured by light transmission aggregometry or by quantifying the percentage of discoid vs. spiked/balloon-shaped platelets using phase-contrast microscopy. The IC50 for inhibition of shape change is 13.73+/-2.52 microM.
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| Animal Protocol |
No specific animal studies have been reported for H2L 5765834. For an LPA1 antagonist, potential in vivo models would include bleomycin-induced pulmonary fibrosis in mice (10-30 mg/kg daily, oral or i.p.), spinal nerve ligation for neuropathic pain, and cancer xenograft studies. Standard endpoints include tissue collagen content (hydroxyproline), histopathology, pain behavior, and tumor volume.
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| ADME/Pharmacokinetics |
Detailed PK data for H2L 5765834 is not available. As a small molecule antagonist (MW 404.33, C21H12N2O₇), it is expected to have moderate oral bioavailability and reasonable plasma exposure in preclinical species. Solubility: DMSO (<40.43 mg/mL). Storage: Powder at -20degC for 3 years, in solvent at -80degC for 1 year.
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| Toxicity/Toxicokinetics |
No toxicity data is publicly available for H2L 5765834. Based on its selectivity for LPA1, LPA3, and LPA5 but not LPA2/LPA4, it is expected to have an improved safety profile compared to pan-LPA receptor antagonists. Potential LPA1-related toxicities in development would include effects on the cardiovascular system and fetal development (LPA1 is involved in embryonic development).
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| References | |
| Additional Infomation |
H2L 5765834 is a research chemical not approved for clinical use. It is a valuable tool for dissecting LPA receptor subtype-specific biology. The selectivity profile (LPA1 >> LPA5 > LPA3; no LPA2/LPA4 activity) makes it useful for identifying which LPA-mediated responses are driven by LPA1 vs. other LPA receptor subtypes in various cell types and tissue contexts.
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| Molecular Formula |
C21H12N2O7
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|---|---|
| Molecular Weight |
404.33
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| Exact Mass |
404.064
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| CAS # |
420841-84-5
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| PubChem CID |
1365686
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
4.474
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
30
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| Complexity |
713
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC(=CC(=C1)OC2=CC=C(C=C2)[N+](=O)[O-])N3C(=O)C4=C(C3=O)C=C(C=C4)C(=O)O
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| InChi Key |
HFYPTENHTPNXGP-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H12N2O7/c24-19-17-9-4-12(21(26)27)10-18(17)20(25)22(19)14-2-1-3-16(11-14)30-15-7-5-13(6-8-15)23(28)29/h1-11H,(H,26,27)
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| Chemical Name |
2-[3-(4-nitrophenoxy)phenyl]-1,3-dioxoisoindole-5-carboxylic 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 |
| 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: 250 mg/mL (618.31 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 | 2.4732 mL | 12.3661 mL | 24.7323 mL | |
| 5 mM | 0.4946 mL | 2.4732 mL | 4.9465 mL | |
| 10 mM | 0.2473 mL | 1.2366 mL | 2.4732 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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