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Purity: ≥98%
Pemirolast potassium (formerly TWT 8152; BMY 26517; TWT-8152; BMY-26517; Alegysal and Alamast), the potassium salt of Pemirolast, is a poten and orally bioactive histamine H1 antagonist and mast cell stabilizer with potential antiallergic effects. For the treatment of asthma, a nonbronchodilator antiallergy medication candidate is being researched.
| Targets |
Histamine H1 receptor
Mast cell (inhibition of degranulation, IC50=0.3 μM) [2] Histamine H1 receptor (H1R) (human H1R, Ki=2.5 nM; rat H1R, Ki=3.2 nM) [3] |
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| ln Vitro |
In vitro activity: Pemirolast potassium (BMY 26517) is a brand-new oral nonbronchodilator antiallergy drug that's currently being tested for use in treating asthma. In addition to being shown to inhibit the release of peptides such as substance P, [2] neurokinin (NK) A, and calcitonin gene-related peptide (CGRP) from sensory nerves, pemirolast potassium (BMY 26517) also inhibits the release of chemical mediators from tissue mast cells.[3] In order to prevent pulmonary hypersensitivity reactions to medications like paclitaxel, pemirolast potassium is used as a treatment for allergic conjunctivitis.[4]
Compound 48/80 (1 μg/mL)-activated rat peritoneal mast cells were treated with Pemirolast potassium (TWT-8152; BMY 26517) (0.01 μM-10 μM). It dose-dependently inhibited histamine and TNF-α release, with 82% inhibition of histamine at 1 μM and IC50=0.3 μM [2] - Histamine (10 μM)-stimulated human conjunctival epithelial cells were treated with Pemirolast potassium (TWT-8152; BMY 26517) (0.1 μM-20 μM). At 5 μM, it reduced IL-8 and MCP-1 secretion by 65% and 58% respectively, and suppressed NF-κB activation by 45% (Western blot) [4] - Primary rat cortical neurons were treated with Pemirolast potassium (TWT-8152; BMY 26517) (1 μM-50 μM). It inhibited histamine-induced intracellular Ca²+ elevation, with EC50=4.8 μM, via blocking H1R-mediated signaling [3] |
| ln Vivo |
Pemirolast potassium (BMY 26517) inhibits the release of substance P in rats, thereby reducing their intake of kaolin. [2] Pemirolast inhibits the release of sensory neuropeptides in rats, thereby potently attenuating hypersensitivity reactions to paclitaxel. [3]
Clinical trial in allergic rhinitis patients: Oral administration of Pemirolast potassium (TWT-8152; BMY 26517) (10 mg twice daily) for 4 weeks reduced nasal symptom score (sneezing, rhinorrhea, pruritus) by 68% compared to placebo. No severe adverse events were reported [1] - Rat passive cutaneous anaphylaxis (PCA) model: Intradermal injection of anti-ovalbumin IgE-sensitized rats were given Pemirolast potassium (TWT-8152; BMY 26517) (5 mg/kg, 10 mg/kg) via oral gavage 1 hour before antigen challenge. The 10 mg/kg dose inhibited skin wheal area by 72% and Evans blue extravasation by 65% [2] - Rabbit allergic conjunctivitis model: Topical instillation of Pemirolast potassium (TWT-8152; BMY 26517) (0.1%, 0.5% w/v) into rabbit eyes twice daily for 7 days reduced histamine-induced conjunctival redness, itching, and edema by 55% (0.1%) and 70% (0.5%) [4] |
| Enzyme Assay |
H1R binding assay: Prepare membrane fractions from HEK293 cells expressing human/rat H1R. Incubate membranes with [3H]-pyrilamine (0.5 nM) and various concentrations of Pemirolast potassium (TWT-8152; BMY 26517) (0.001 nM-100 nM) at 25°C for 60 minutes. Separate bound and free ligand by vacuum filtration through glass fiber filters. Measure radioactivity with a liquid scintillation counter and calculate Ki values using the Cheng-Prusoff equation [3]
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| Cell Assay |
Mast cell degranulation assay: Isolate rat peritoneal mast cells via peritoneal lavage. Resuspend cells in buffer and pre-treat with Pemirolast potassium (TWT-8152; BMY 26517) (0.01 μM-10 μM) for 30 minutes. Stimulate with compound 48/80 (1 μg/mL) for 60 minutes at 37°C. Centrifuge to collect supernatant, measure histamine via fluorometric assay and TNF-α via ELISA [2]
- Conjunctival epithelial cell cytokine secretion assay: Seed human conjunctival epithelial cells in 24-well plates and incubate for 24 hours. Pre-treat with Pemirolast potassium (TWT-8152; BMY 26517) (0.1 μM-20 μM) for 1 hour, then stimulate with histamine (10 μM) for 24 hours. Collect supernatant to quantify IL-8/MCP-1 via ELISA; extract nuclear protein to detect NF-κB activation via Western blot [4] - Neuronal Ca²+ elevation assay: Culture primary rat cortical neurons in 96-well plates for 7 days. Load cells with Ca²+ fluorescent probe, then treat with Pemirolast potassium (TWT-8152; BMY 26517) (1 μM-50 μM) for 30 minutes. Stimulate with histamine (10 μM) and monitor fluorescence intensity in real-time to calculate EC50 [3] |
| Animal Protocol |
Rats Rat PCA model: Male Wistar rats (180-220 g) were intradermally injected with anti-ovalbumin IgE (0.1 mL) on the back. After 48 hours, Pemirolast potassium (TWT-8152; BMY 26517) was dissolved in physiological saline and administered via oral gavage (5 mg/kg, 10 mg/kg). One hour later, intravenous injection of ovalbumin (1 mg/kg) + Evans blue (5 mg/kg) was given. Thirty minutes later, rats were euthanized, and skin wheal area and Evans blue extravasation were measured [2] - Rabbit allergic conjunctivitis model: Male New Zealand white rabbits (2.0-2.5 kg) were sensitized with ovalbumin (100 μg) + aluminum hydroxide via subcutaneous injection on days 0 and 7. On day 14, Pemirolast potassium (TWT-8152; BMY 26517) was prepared as 0.1% and 0.5% w/v aqueous solutions and instilled into both eyes (50 μL/eye) twice daily for 7 days. On day 21, conjunctival challenge with ovalbumin (1% solution) was performed, and ocular symptoms (redness, itching, edema) were scored at 30 minutes post-challenge [4] |
| ADME/Pharmacokinetics |
Absorption: Oral bioavailability in humans is 50-55%; peak plasma concentration (Cmax) is reached 2-3 hours after oral administration (10 mg dose: Cmax = 110 ng/mL) [1]
- Distribution: Volume of distribution (Vd) in humans is 1.8 L/kg; brain/plasma concentration ratio <0.02, indicating negligible blood-brain barrier penetration [3] - Metabolism: Very little metabolism in the liver; >80% of the dose is excreted unchanged [1] - Excretion: 75% of the dose is excreted in urine and 20% in feces. Elimination half-life (t1/2) in humans is 4-6 hours [1] - Plasma protein binding rate: The plasma protein binding rate of piperidone potassium (TWT-8152; BMY 26517) in human plasma is 25-30% [3] |
| Toxicity/Toxicokinetics |
Acute toxicity: LD50 in rats and mice > 2000 mg/kg (oral); no deaths or serious clinical symptoms were reported [2] - Chronic toxicity: No significant hepatotoxicity or hematologic abnormalities were observed in rats after oral administration of Pemirolast potassium (TWT-8152; BMY 26517) (100 mg/kg/day) for 6 consecutive months [2] - Clinical side effects: Mild headache (2-3% of patients), dry mouth (1-2%) and mild gastrointestinal discomfort (1%) have been reported. No sedative, anticholinergic or cardiotoxic side effects were observed at therapeutic doses [1,4] - Drug interactions: No significant interactions with antihistamines, corticosteroids or other commonly used drugs [1]
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| References | |
| Additional Infomation |
Pemirolast potassium is the potassium salt form of piperamifloxacin, a pyrimidinone derivative with anti-allergic properties. Piperamifloxacin potassium exerts its effects by blocking antigen-mediated calcium ion influx into mast cells. This prevents mast cell degranulation, thereby stabilizing mast cells and inhibiting the release of inflammatory mediators histamine and leukotrienes involved in the allergic process. Piperamifloxacin potassium also inhibits the release of inflammatory mediators from eosinophils. Piperamifloxacin potassium (TWT-8152; BMY 26517) is a nonsteroidal anti-allergic drug and mast cell stabilizer with selective H1R antagonistic activity [1,2,3,4]. Its core mechanisms include mast cell membrane stabilization (inhibition of histamine/TNF-α release), competitive H1R antagonism, and inhibition of NF-κB-mediated inflammatory cytokine secretion [2,3,4].
Indications include allergic rhinitis, allergic conjunctivitis and chronic urticaria, which can relieve sneezing, runny nose, itchy eyes and skin damage [1,4]. Its blood-brain barrier penetration is extremely low, so it does not have a sedative effect, which distinguishes it from the first-generation pyrosten potassium. Antihistamines [3] Available in both oral tablets and ophthalmic solutions, topical application (ophthalmic) has a rapid onset of action (15-30 minutes) and can relieve ocular allergy symptoms [4]. It has very low metabolism, low plasma protein binding rate, and good safety, making it suitable for long-term use in the treatment of allergic diseases [1,2]. |
| Molecular Formula |
C10H7KN6O
|
|---|---|
| Molecular Weight |
266.3
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| Exact Mass |
266.031
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| Elemental Analysis |
C, 45.10; H, 2.65; K, 14.68; N, 31.56; O, 6.01
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| CAS # |
100299-08-9
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| Related CAS # |
Pemirolast; 69372-19-6
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| PubChem CID |
443866
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| Appearance |
Light yellow to green yellow solid powder
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| Boiling Point |
454.8ºC at 760mmHg
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| Melting Point |
310-311ºC (dec.)
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| Flash Point |
228.9ºC
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| Vapour Pressure |
1.85E-08mmHg at 25°C
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
18
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| Complexity |
495
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C1C(C2=N[N-]N=N2)=CN=C3N1C=CC=C3C.[K+]
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| InChi Key |
NMMVKSMGBDRONO-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C10H7N6O.K/c1-6-3-2-4-16-9(6)11-5-7(10(16)17)8-12-14-15-13-8;/h2-5H,1H3;/q-1;+1
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| Chemical Name |
potassium;9-methyl-3-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)pyrido[1,2-a]pyrimidin-4-one
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| Synonyms |
TWT-8152; BMY 26517; TWT 8152; BMY 26517; TWT8152; BMY 26517; Pemirolast; Pemirolast potassium. trade name: Alegysal and Alamast.
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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: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 100 mg/mL (375.52 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.7552 mL | 18.7758 mL | 37.5516 mL | |
| 5 mM | 0.7510 mL | 3.7552 mL | 7.5103 mL | |
| 10 mM | 0.3755 mL | 1.8776 mL | 3.7552 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT02517372 | Completed | Drug: CRD007 | Healthy Volunteers | RSPR Pharma AB | October 2014 | Phase 1 |
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