| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
LPA1 Receptor 2.7 nM (IC50)
Targets lysophosphatidic acid receptor 1 (LPA1) as a highly potent and specific antagonist. ONO-9780307 binds to an orthosteric site within the LPA1 receptor, competitively blocking the binding of endogenous LPA and preventing LPA1-mediated Gi-coupled signaling activation. |
|---|---|
| ln Vitro |
The LPA1-B103 and Vector-B103 cells exhibit 0.1~10000 μM of VT107, which inhibits Ca2+ mobilization[1]. ONO-9780307 interacts to an orthosteric location in LPA1 and is employed to solve the crystal structure of that protein[1].
In vitro, ONO-9780307 effectively blocks LPA-induced calcium mobilization, ERK1/2 phosphorylation, and cell migration in LPA1-expressing cell lines with an IC50 of 2.7 nM. As a tool compound, it has been used to solve the LPA1 crystal structure, confirming its orthosteric binding mode and interactions with specific residues in the LPA1 binding pocket. |
| ln Vivo |
Detailed in vivo activity data for ONO-9780307 is not publicly available. As a potent LPA1 antagonist (IC50=2.7 nM), it has potential applications in research models of fibrosis, neuropathic pain, cancer, and inflammatory diseases, but no published animal efficacy studies with this specific compound are currently available.
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| Enzyme Assay |
Cell-free radioligand binding assays are performed using membranes from LPA1-expressing CHO or HEK293 cells. Membranes (10 microg/well) 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 ONO-9780307 concentrations (0.01 nM-10 microM) for 60 min at 25degC. Nonspecific binding is determined with 10 microM unlabeled LPA. Bound radioactivity is separated by filtration and counted.
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| Cell Assay |
CHO-K1 cells stably expressing human LPA1 are loaded with Fluo-4 AM calcium indicator (4 microM) in HBSS buffer with 20 mM HEPES and 2.5 mM probenecid for 30 min at 37degC. Cells are washed and pre-incubated with ONO-9780307 (0.01-1000 nM) for 15 min, then stimulated with LPA (3-10 nM, EC80). Fluorescence is measured using a FLIPR or plate reader. Antagonist IC50 is calculated from the inhibition curve (2.7 nM). Compounds are also tested in cell migration (Boyden chamber) and proliferation (MTT) assays.
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| Animal Protocol |
No specific animal studies have been reported for ONO-9780307. For an LPA1 antagonist with 2.7 nM potency, potential in vivo models would include bleomycin-induced pulmonary fibrosis (5-30 mg/kg daily i.p. or oral), spinal nerve ligation for neuropathic pain, and cancer xenograft models. Standard endpoints include lung collagen content (hydroxyproline), histopathology, pain behavior, and tumor volume.
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| ADME/Pharmacokinetics |
Detailed PK data for ONO-9780307 is not publicly available. ONO-9780307 has a molecular weight of 521.60, formula C30H3₅NO₇, and purity ≥98%. Solubility: DMSO 100-190 mg/mL. Storage: 4degC, protect from light. As a small molecule antagonist, it would be expected to have reasonable oral bioavailability and moderate clearance in preclinical species.
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| Toxicity/Toxicokinetics |
No toxicity data is publicly available for ONO-9780307. As a highly potent and specific LPA1 antagonist, potential safety concerns may relate to off-target interactions (unlikely given specificity) or on-target effects of LPA1 inhibition, which could affect embryonic development, CNS function, and cardiovascular homeostasis. Standard safety assessments would be required for therapeutic development.
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| References | |
| Additional Infomation |
ONO-9780307 is a research chemical not approved for clinical use. It is notable for having been used to solve the crystal structure of the LPA1 receptor (bound in the orthosteric site), making it an extremely valuable tool for structural biology studies of LPA1 and for rational drug design. It is also one of the most potent synthetic LPA1 antagonists reported to date.
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| Molecular Formula |
C31H37NO6
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|---|---|
| Molecular Weight |
519.63
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| Exact Mass |
521.241
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| CAS # |
856691-44-6
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| PubChem CID |
11785732
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| Appearance |
White to off-white solid powder
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| LogP |
3.9
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
12
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| Heavy Atom Count |
38
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| Complexity |
765
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| Defined Atom Stereocenter Count |
2
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| SMILES |
COC1=C(C)C(OC)=CC([C@H]([C@@](CN2C=C(C(OC)=O)C(=C2)CC(O)=O)([H])CC2CC3C(=CC=CC=3)C2)C)=C1
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| InChi Key |
PMPFDANPLYTSTM-PWUYWRBVSA-N
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| InChi Code |
InChI=1S/C30H35NO7/c1-18-26(36-2)12-22(13-27(18)37-3)29(34)24(11-19-9-20-7-5-6-8-21(20)10-19)16-31-15-23(14-28(32)33)25(17-31)30(35)38-4/h5-8,12-13,15,17,19,24,29,34H,9-11,14,16H2,1-4H3,(H,32,33)/t24-,29+/m0/s1
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| Chemical Name |
2-[1-[(2S,3S)-2-(2,3-dihydro-1H-inden-2-ylmethyl)-3-(3,5-dimethoxy-4-methylphenyl)-3-hydroxypropyl]-4-methoxycarbonylpyrrol-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: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 (191.72 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (9.59 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 50.0 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 | 1.9244 mL | 9.6222 mL | 19.2445 mL | |
| 5 mM | 0.3849 mL | 1.9244 mL | 3.8489 mL | |
| 10 mM | 0.1924 mL | 0.9622 mL | 1.9244 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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