| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg | |||
| 100mg | |||
| Other Sizes |
| Targets |
ONO-0300302 targets the lysophosphatidic acid receptor 1 (LPA1), a G-protein-coupled receptor involved in various physiological and pathological processes. As a slow tight binding antagonist, its binding affinity increases with time, with a Kd of 0.34 nM at 37°C for 2 hours. LPA1 antagonism reduces LPA-induced smooth muscle contraction, making it a promising target for BPH.
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| ln Vitro |
The stability of ONO-0300302 against rat microsomes is moderate [1].
In vitro, ONO-0300302 acts as a slow tight binding LPA1 antagonist with high potency (IC50: 0.16 nM). Its binding affinity increases with time, with a Kd of 0.34 nM at 37°C for 2 hours. Its in vitro activity is assessed using receptor binding assays and functional assays measuring LPA-induced signaling in cells expressing the LPA1 receptor. |
| ln Vivo |
Over the course of 12 hours, ONO-0300302 considerably reduces the increase in intraurethral pressure (IUP) that is caused by the lysophosphatidic acid receptor (LPA) in rats (3 mg/kg, p.o.) and dogs (1 mg/kg, p.o.) [1].
In vivo activity of ONO-0300302 has been demonstrated in rat and dog models, where it significantly inhibits LPA-induced increase of intraurethral pressure (IUP) at doses of 3 mg/kg (rat) and 1 mg/kg (dog) orally, with effects lasting over 12 hours. This demonstrates its oral bioavailability and sustained efficacy in vivo. |
| Enzyme Assay |
The in vitro receptor binding assay for ONO-0300302 involves measuring its affinity for the LPA1 receptor using radioligand binding techniques. These assays use membrane preparations from cells expressing the LPA1 receptor and measure the displacement of a labeled ligand by the compound. As a slow tight binding antagonist, its binding affinity increases with time, with a Kd of 0.34 nM at 37°C for 2 hours. Inhibitory potency (IC50 of 0.16 nM) is determined.
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| Cell Assay |
In vitro cellular assays for ONO-0300302 are performed using cells expressing the human LPA1 receptor. These assays measure the compound's ability to antagonize LPA-induced signaling, such as calcium mobilization or GTPγS binding. The compound's slow tight binding特性 is demonstrated by the time-dependent increase in its inhibitory activity. These assays confirm its potent and selective LPA1 antagonism.
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| Animal Protocol |
In vivo animal studies for ONO-0300302 are conducted in rat and dog models measuring LPA-induced increase of intraurethral pressure (IUP). These studies typically involve oral administration of the compound, followed by LPA challenge and measurement of IUP. The compound significantly inhibits LPA-induced IUP at doses of 3 mg/kg (rat) and 1 mg/kg (dog) orally, with effects lasting over 12 hours. These studies demonstrate its oral efficacy and duration of action.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of ONO-0300302 are characterized by oral bioavailability and sustained efficacy. Following oral administration, the compound achieves sufficient systemic exposure to inhibit LPA1 receptors in the target tissues. Its pharmacokinetic profile supports once-daily dosing for the treatment of BPH, with effects lasting over 12 hours in preclinical models.
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| Toxicity/Toxicokinetics |
Toxicology studies of ONO-0300302 have been conducted to support its development for BPH. These studies include acute and repeat-dose toxicity assessments in preclinical species, as well as genotoxicity and safety pharmacology evaluations. As an LPA1 antagonist, its toxicology profile includes effects on smooth muscle function and potential for off-target effects.
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| References | |
| Additional Infomation |
ONO-0300302 is a slow tight binding LPA1 antagonist with high potency (IC50: 0.16 nM) being developed for the treatment of benign prostatic hyperplasia (BPH). It significantly inhibits LPA-induced increase of intraurethral pressure (IUP) in rat and dog models over 12 hours. Its slow tight binding特性 provides sustained receptor occupancy and efficacy.
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| Molecular Formula |
C29H35NO5
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|---|---|
| Molecular Weight |
477.591908693314
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| Exact Mass |
477.251
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| CAS # |
856689-51-5
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| PubChem CID |
11317548
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
4.4
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
11
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| Heavy Atom Count |
35
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| Complexity |
646
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| Defined Atom Stereocenter Count |
2
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| SMILES |
O[C@H](C1C=C(C(C)=C(C=1)OC)OC)[C@H](CN1C=CC(CCC(=O)O)=C1)CC1CC2C=CC=CC=2C1
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| InChi Key |
USAXUWZJQPBEDO-ABYGYWHVSA-N
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| InChi Code |
InChI=1S/C29H35NO5/c1-19-26(34-2)15-24(16-27(19)35-3)29(33)25(14-21-12-22-6-4-5-7-23(22)13-21)18-30-11-10-20(17-30)8-9-28(31)32/h4-7,10-11,15-17,21,25,29,33H,8-9,12-14,18H2,1-3H3,(H,31,32)/t25-,29+/m0/s1
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| Chemical Name |
3-[1-[(2S,3S)-2-(2,3-dihydro-1H-inden-2-ylmethyl)-3-(3,5-dimethoxy-4-methylphenyl)-3-hydroxypropyl]pyrrol-3-yl]propanoic acid
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| Synonyms |
ONO0300302; ONO 0300302; ONO-0300302
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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 : ~220 mg/mL (~460.65 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5.5 mg/mL (11.52 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 55.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 2: ≥ 5.5 mg/mL (11.52 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 55.0 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 | 2.0938 mL | 10.4692 mL | 20.9385 mL | |
| 5 mM | 0.4188 mL | 2.0938 mL | 4.1877 mL | |
| 10 mM | 0.2094 mL | 1.0469 mL | 2.0938 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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