| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
Linaprazan specifically targets the gastric H+,K+-ATPase (proton pump) located on the secretory membrane of parietal cells. It acts as a K+-competitive inhibitor with an IC50 of 1.0 +/- 0.2 uM. Unlike traditional PPIs which form covalent disulfide bonds with the pump, Linaprazan binds reversibly to the K+-binding site, causing rapid and pH-independent inhibition of acid secretion. It also modulates the KCNH2/KCNH6 potassium channel.
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| ln Vitro |
In cell-free enzyme assays, Linaprazan inhibits gastric H+,K+-ATPase with an IC50 of 1.0 +/- 0.2 uM via K+-competitive binding. In isolated rabbit gastric glands, it inhibits histamine- or dibutyryl-cAMP-induced acid production with IC50s of 0.28 and 0.26 uM, respectively. In vitro, Linaprazan has a Ki value of 46 nM and a pIC50 of 6.5. It reduces porcine renal Na+,K+-ATPase activity by only 9 +/- 2%, indicating selectivity for the gastric proton pump.
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| ln Vivo |
In vivo, Linaprazan exhibits potent and long-lasting acid suppression. Animal administration references recommend doses of 0.5-1.0 mg/kg. In clinical studies, the 75 mg dose of Linaprazan achieved an 89% healing rate of reflux esophagitis at 4 weeks, with a greater degree of acid suppression compared to esomeprazole 40 mg. It is an effective reversible inhibitor of gastric acid secretion for the treatment of acid-related diseases.
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| Enzyme Assay |
The in vitro H+,K+-ATPase inhibition assay uses porcine gastric vesicles or isolated gastric glands. Membranes (10 ug protein) are incubated in buffer containing 10 mM PIPES, 140 mM KCl, 1 mM MgCl2, and 1 mM ATP at pH 7.4. Linaprazan is serially diluted (0.01-100 uM) and added to the reaction. After 30 minutes at 37degC, the reaction is stopped, and inorganic phosphate (Pi) released is measured using the malachite green method. The IC50 is calculated from the concentration-inhibition curve. Alternatively, a [3H]-SCH 28080 competitive binding assay can be performed using rabbit gastric membrane preparations.
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| Cell Assay |
For in vitro cellular assays, rabbit gastric glands are isolated from New Zealand White rabbits via collagenase digestion. Isolated glands are suspended in Hanks‘ balanced salt solution and seeded in 24-well plates. Glands are pre-incubated with Linaprazan (0.01-10 uM) for 15 minutes, then stimulated with 100 uM histamine (or 1 mM dibutyryl-cAMP) for 60 minutes at 37degC. Acid production is assessed by measuring the accumulation of 14C-aminopyrine (AP) into the glands. The ratio of intracellular to extracellular AP is calculated, and IC50 values are determined from dose-response curves.
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| Animal Protocol |
An in vivo protocol for Linaprazan uses a pylorus-ligated rat model of gastric acid secretion. Male Sprague-Dawley rats (200-250 g) are fasted for 24 hours but allowed free access to water. Under isoflurane anesthesia, the pylorus is ligated. Linaprazan is administered intraduodenally at doses of 0.1-10 mg/kg immediately after ligation. After 4 hours, rats are euthanized, and gastric contents are collected. Gastric juice volume and pH are measured, and total acid output (mEq/4 h) is determined by titration with 0.1 N NaOH to pH 7.0. Percent inhibition of acid secretion is calculated relative to the vehicle control group.
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| ADME/Pharmacokinetics |
Detailed pharmacokinetic parameters for Linaprazan have not been published. As a reversible potassium-competitive acid blocker (P-CAB), it concentrates highly in the gastric parietal cell canaliculus. Linaprazan is expected to have moderate oral bioavailability and is rapidly absorbed following oral administration. The terminal half-life is likely short, consistent with reversible binding inhibitors. Metabolism is expected to occur via hepatic cytochrome P450 enzymes. For research purposes, the compound is formulated in DMSO for in vitro studies and in vehicle (e.g., 0.5% methylcellulose or 10% DMSO/40% PEG300/5% Tween 80/45% saline) for in vivo administration.
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| Toxicity/Toxicokinetics |
Specific toxicological data for Linaprazan is not available. As a potassium-competitive acid blocker, the most common adverse effects are expected to be gastrointestinal in nature, including diarrhea, nausea, and abdominal pain. Long-term acid suppression may be associated with an increased risk of gastrointestinal infections, vitamin B12 deficiency, and osteoporosis-related fractures. Standard preclinical toxicology studies would include 28-day repeat-dose oral toxicity studies in rats and dogs to evaluate target organ toxicity.
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| References |
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| Additional Infomation |
Linaprazan is a lipophilic weak base with potassium-competitive acid-blocking (P-CAB) activity. Linaprazan is highly concentrated in the parietal cell tubules of the stomach. Upon entering an acidic environment, it is immediately protonated and competitively and reversibly binds to the potassium-binding site of the proton pump H+/K+ ATPase, thereby inhibiting the pump's activity and the secretion of H+ ions from the parietal cells into the gastric lumen—the final step in gastric acid production.
Linaprazan is a research-grade chemical and is not approved for clinical use. Its molecular formula is C21H26N4O2 with a molecular weight of 366.46 and a purity of ≥98%. It is a potent and selective acid pump antagonist (potassium-competitive acid blocker) that reversibly inhibits gastric H+,K+-ATPase (IC50 = 1.0 uM). Linaprazan is an important tool for studying acid secretion mechanisms and for the development of novel therapies for gastroesophageal reflux disease (GERD) and other acid-related disorders. |
| Molecular Formula |
C21H26N4O2
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|---|---|
| Molecular Weight |
366.46
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| Exact Mass |
366.206
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| CAS # |
248919-64-4
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| PubChem CID |
9951066
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| Appearance |
White to off-white solid powder
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| LogP |
3.549
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
27
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| Complexity |
493
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=C(C(=CC=C1)C)CNC2=CC(=CN3C2=NC(=C3C)C)C(=O)NCCO
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| InChi Key |
GHVIMBCFLRTFHI-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H26N4O2/c1-13-6-5-7-14(2)18(13)11-23-19-10-17(21(27)22-8-9-26)12-25-16(4)15(3)24-20(19)25/h5-7,10,12,23,26H,8-9,11H2,1-4H3,(H,22,27)
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| Chemical Name |
8-[(2,6-dimethylphenyl)methylamino]-N-(2-hydroxyethyl)-2,3-dimethylimidazo[1,2-a]pyridine-6-carboxamide
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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: ≥ 35 mg/mL (95.51 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 | 2.7288 mL | 13.6441 mL | 27.2881 mL | |
| 5 mM | 0.5458 mL | 2.7288 mL | 5.4576 mL | |
| 10 mM | 0.2729 mL | 1.3644 mL | 2.7288 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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