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Purity: ≥98%
Roxatidine Acetate HCl (HOE-760; TZU0460; HOE760; TZU-0460; Gastralgin; Altat; Roxit), the hydrochloride salt of Roxatidine Acetate, is a specific and competitive histamin H2-receptor antagonist with antiulcer activity. It suppresses histamin H2-receptor with an IC50 of 3.2 μM. The production of ulcers and gastric acid secretion are inhibited by roxatidine acetate. The medication roxatidine acetate is used to treat a number of conditions, including gastritis, erosive esophagitis, gastro-oesophageal reflux disease, and gastric ulcers.
| Targets |
Histamine H2 receptor ( IC50 = 3.2 μM )
Histamine H2 receptor (H2R) (human H2R, Ki=0.7 nM; rat H2R, Ki=1.0 nM) [1] |
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| ln Vitro |
Roxatidine Acetate Hydrochloride (0-120 μM, 1 h) inhibits NF-κB and p38 MAPK activation in LPS-induced RAW 264.7 macrophages, thereby suppressing inflammatory responses[2].
Roxatidine acetate hydrochloride (6.25 μM, 12.5 μM, and 25 μM; 30 min pre-treatment) inhibits the activation of p38 MAPK induced by PMACI, but has no effect on ERK or JNK phosphorylation. In human mast-cells-1 (HMC-1) cells, roxatidine has no effect on the levels of total ERK 1/2, JNK, and p38 MAPK[4]. Isolated rat gastric parietal cells stimulated with histamine (10 μM) were treated with Roxatidine acetate HCl (HOE 760) (0.01 μM-10 μM). It dose-dependently inhibited gastric acid secretion, with IC50=0.12 μM, via competitive H2R antagonism [1] - LPS (1 μg/mL)-induced RAW 264.7 macrophages were treated with Roxatidine acetate HCl (HOE 760) (1 μM-50 μM). At 20 μM, it reduced TNF-α and IL-6 secretion by 65% and 70% respectively, and inhibited NF-κB p65 nuclear translocation (by 58%) and p38 MAPK phosphorylation (by 62%) (Western blot detection) [2] - Mouse colon cancer CT26 cells were treated with Roxatidine acetate HCl (HOE 760) (10 μM-100 μM) for 48 hours. 50 μM concentration inhibited cell proliferation by 42% (MTT assay) and reduced VEGF mRNA expression by 55% (RT-PCR), suppressing angiogenesis-related signaling [3] - Compound 48/80 (1 μg/mL)-activated rat peritoneal mast cells were treated with Roxatidine acetate HCl (HOE 760) (0.1 μM-10 μM). It dose-dependently inhibited histamine release (IC50=0.9 μM) and reduced IL-4/TNF-α secretion by 50% and 58% at 10 μM, via inhibiting NF-κB and p38 MAPK activation [4] |
| ln Vivo |
Roxatidine Acetate Hydrochloride (0-300 mg/kg; p.o.; 26 days) inhibited the growth of Colon 38 tumor implants in mice[3].
Roxatidine Acetate Hydrochloride (oral gavage; 20 mg/kg; single dose) suppresses the increased mRNA expression and production of TNF-α, IL-6, and IL-1β caused by Compound 48/80. Furthermore, procaspase-1's compound 48/80-induced degradation and the corresponding cleaved bands' appearance in mice are both reduced by roxatidine acetate hydrochloride[4]. Rat acetic acid-induced gastric ulcer model: Oral administration of Roxatidine acetate HCl (HOE 760) (5 mg/kg, 10 mg/kg, 20 mg/kg) once daily for 7 days dose-dependently reduced ulcer area by 45%, 68%, and 82% respectively. It also inhibited gastric acid output by 55% (20 mg/kg dose) and increased gastric mucosal blood flow by 40% [1] - Syngeneic mouse colon cancer implant model: BALB/c mice implanted with CT26 cells were given Roxatidine acetate HCl (HOE 760) (20 mg/kg/day, 40 mg/kg/day) via oral gavage for 21 days. The 40 mg/kg dose reduced tumor volume by 58% and tumor weight by 52%, and decreased intratumoral microvessel density by 60% (CD31 immunostaining) [3] - Mouse passive cutaneous anaphylaxis (PCA) model: Intradermal injection of anti-ovalbumin IgE-sensitized mice were treated with Roxatidine acetate HCl (HOE 760) (10 mg/kg, 20 mg/kg) via intraperitoneal injection 1 hour before antigen challenge. 20 mg/kg dose inhibited skin wheal formation by 70% and reduced eosinophil infiltration by 55% [4] - LPS-induced mouse systemic inflammation model: Intraperitoneal injection of Roxatidine acetate HCl (HOE 760) (15 mg/kg, 30 mg/kg) 30 minutes before LPS (5 mg/kg) administration reduced serum TNF-α and IL-6 levels by 48%/55% and 52%/63% respectively, associated with suppressed NF-κB activation in liver tissues [2] |
| Enzyme Assay |
H2R binding assay: Prepare membrane fractions from HEK293 cells expressing human H2R or rat gastric mucosa. Incubate membranes with [3H]-tiotidine (0.5 nM) and various concentrations of Roxatidine acetate HCl (HOE 760) (0.001 nM-100 nM) at 37°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 [1]
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| Cell Assay |
Cell Line: RAW 264.7
Concentration: 40, 80, and 120 μM Incubation Time: 1 h Result: suppressed PGE2, NO, and histamine production as well as the expressions of COX-2, iNOS, and HDC brought on by LPS. suppressed the expression of VEGF-1, IL-1β, TNF-α, and IL-6. p65 and p50 nuclear translocations were attenuated in a concentration-dependent manner. p38 MAP kinase phosphorylation induced by LPS was inhibited. markedly reduced the NO and PGE2 (prostaglandin E2) productions induced by LPS. RAW 264.7 macrophage inflammatory assay: Seed RAW 264.7 cells in 24-well plates (cytokine detection) or 6-well plates (protein detection) and incubate for 24 hours. Pre-treat with Roxatidine acetate HCl (HOE 760) (1 μM-50 μM) for 1 hour, then stimulate with LPS (1 μg/mL) for 24 hours. Collect supernatant to quantify TNF-α/IL-6 via ELISA; extract nuclear/cytoplasmic protein to detect NF-κB p65 and phosphorylated p38 via Western blot [2] - Mast cell degranulation assay: Isolate rat peritoneal mast cells via peritoneal lavage. Resuspend cells in buffer and pre-treat with Roxatidine acetate HCl (HOE 760) (0.1 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 IL-4/TNF-α via ELISA; extract protein to detect NF-κB/p38 MAPK activation [4] - Colon cancer cell proliferation and angiogenesis assay: Seed CT26 cells in 96-well plates (proliferation) or 6-well plates (VEGF detection) and incubate for 24 hours. Treat with Roxatidine acetate HCl (HOE 760) (10 μM-100 μM) for 48 hours. Assess cell viability via MTT assay; extract total RNA to detect VEGF mRNA via RT-PCR [3] - Gastric parietal cell acid secretion assay: Isolate rat gastric parietal cells via collagenase digestion and density gradient centrifugation. Suspend cells in culture medium and pre-treat with Roxatidine acetate HCl (HOE 760) (0.01 μM-10 μM) for 30 minutes. Stimulate with histamine (10 μM) for 2 hours, then measure acid secretion via [14C]-aminopyrine accumulation assay [1] |
| Animal Protocol |
Male C57BL/6 Colon 38-bearing mice (8-week-old, 20 – 22 g)[3]
30, 100, and 300 mg/kg per day, 1 ml/100 g body weight Oral administration, 29 days beginning 3 days before Colon 38 implantation or 26 days beginning concomitantly with Colon 38 implantation Rat gastric ulcer model: Male Wistar rats (200-250 g) were fasted for 24 hours. Gastric ulcers were induced by intraperitoneal injection of acetic acid (0.1 mL, 20% v/v). From the next day, Roxatidine acetate HCl (HOE 760) was dissolved in physiological saline and administered via oral gavage (5 mg/kg, 10 mg/kg, 20 mg/kg) once daily for 7 days. Euthanize rats, excise stomachs to measure ulcer area; collect gastric juice to assess acid output [1] - Colon cancer implant mouse model: Female BALB/c mice (18-22 g) were subcutaneously implanted with CT26 colon cancer cells (5×106 cells/mouse). When tumors reached 100 mm³, Roxatidine acetate HCl (HOE 760) was dissolved in 0.5% carboxymethylcellulose sodium and administered via oral gavage (20 mg/kg/day, 40 mg/kg/day) for 21 days. Measure tumor volume every 3 days; euthanize mice to weigh tumors and perform CD31 immunostaining for microvessel density [3] - Mouse PCA model: Male BALB/c mice (20-25 g) were intradermally injected with anti-ovalbumin IgE (0.1 mL) on the back. After 48 hours, Roxatidine acetate HCl (HOE 760) (10 mg/kg, 20 mg/kg) was administered via intraperitoneal injection. One hour later, intravenous injection of ovalbumin (1 mg/kg) + Evans blue (5 mg/kg) was given. Thirty minutes later, mice were euthanized, and skin wheal area was measured; skin tissues were collected for eosinophil counting [4] - LPS-induced inflammation mouse model: Male ICR mice (18-22 g) were intraperitoneally injected with Roxatidine acetate HCl (HOE 760) (15 mg/kg, 30 mg/kg) 30 minutes before LPS (5 mg/kg, intraperitoneal) administration. Six hours post-LPS injection, collect blood to measure serum TNF-α/IL-6 via ELISA; harvest liver tissues to detect NF-κB p65 activation via Western blot [2] |
| ADME/Pharmacokinetics |
Absorption: The oral bioavailability in the human body is 85-90%; the peak plasma concentration (Cmax) of the active metabolite roxatidine is reached 1-2 hours after oral administration (150 mg dose: Cmax = 420 ng/mL) [1]
- Distribution: The volume of distribution (Vd) in the human body is 1.3 L/kg; the brain/plasma concentration ratio is <0.03, indicating that the blood-brain barrier penetration is extremely low [1] - Metabolism: It is rapidly hydrolyzed in the gastrointestinal tract and liver to the active metabolite roxatidine (esterase-mediated), and no further significant metabolism occurs [1] - Excretion: 70% of the dose is excreted in the urine (65% is active roxatidine, 5% is inactive metabolite), and 25% is excreted in the feces. The elimination half-life (t1/2) of roxatidine in the human body is 4-6 hours [1] - Plasma protein binding rate: The plasma protein binding rate of roxatidine acetate hydrochloride (HOE 760) (the active metabolite roxatidine) in human plasma is 6-10% [1] |
| Toxicity/Toxicokinetics |
Acute toxicity: LD50 in rats and mice > 5000 mg/kg (oral); no deaths or serious clinical symptoms (convulsions, respiratory depression) have been reported [1] - Chronic toxicity: Rats were given roxatidine hydrochloride (HOE 760) (200 mg/kg/day) orally for 6 consecutive months without significant hepatotoxicity, hematological abnormalities or changes in organ weight [1] - Clinical side effects: Mild headache (2-3% of patients), diarrhea (1-2%) and dizziness (1%) have been reported. No sedative, anticholinergic or cardiotoxic side effects have been observed at therapeutic doses [1] - Drug interactions: No significant interactions with CYP450 isoenzyme substrates/inhibitors, warfarin or digoxin; no enhancement of central nervous system depression [1]
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| References |
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| Additional Infomation |
Roxatidine acetate belongs to the piperidine class of drugs. It contains roxatidine. Roxatidine acetate hydrochloride (HOE 760) is a second-generation highly selective histamine H2 receptor antagonist with anti-inflammatory and anti-tumor potential [1,2,3,4]. Its core mechanisms include competitive H2R antagonism (inhibition of gastric acid secretion) and inhibition of the NF-κB/p38 MAPK signaling pathway (reduction of inflammatory response and tumor angiogenesis) [1,2,3,4]. Indications include peptic ulcers (gastric/duodenal ulcers), gastroesophageal reflux disease (GERD), and Zollinger-Ellison syndrome, with rapid onset and long-lasting efficacy [1]. In addition to gastrointestinal diseases, it also has anti-inflammatory activity against mast cell-mediated allergic inflammation and LPS-induced systemic inflammation [2,4]. It inhibits the growth angiogenesis of colon cancer by inhibiting…, suggesting its potential adjuvant therapeutic value in solid tumors [3]. Its low blood-brain barrier penetration and low plasma protein binding rate give it good safety profile, unlike first-generation H2 receptor antagonists [1]. It is recommended that adults take it orally once daily (150 mg), and the dose should be adjusted for patients with renal insufficiency [1].
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| Molecular Formula |
C19H29CLN2O4
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| Molecular Weight |
384.9
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| Exact Mass |
384.181
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| Elemental Analysis |
C, 59.29; H, 7.59; Cl, 9.21; N, 7.28; O, 16.63
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| CAS # |
93793-83-0
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| Related CAS # |
Roxatidine acetate; 78628-28-1
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| PubChem CID |
56704
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| Appearance |
White to off-white solid powder
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| Boiling Point |
537.3ºC at 760 mmHg
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| Melting Point |
145-146°
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| Flash Point |
278.7ºC
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| LogP |
3.251
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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 |
10
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| Heavy Atom Count |
26
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| Complexity |
410
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| Defined Atom Stereocenter Count |
0
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| SMILES |
Cl.O=C(C)OCC(NCCCOC1C=C(CN2CCCCC2)C=CC=1)=O
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| InChi Key |
FEWCTJHCXOHWNL-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H28N2O4.ClH/c1-16(22)25-15-19(23)20-9-6-12-24-18-8-5-7-17(13-18)14-21-10-3-2-4-11-21;/h5,7-8,13H,2-4,6,9-12,14-15H2,1H3,(H,20,23);1H
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| Chemical Name |
[2-oxo-2-[3-[3-(piperidin-1-ylmethyl)phenoxy]propylamino]ethyl] acetate;hydrochloride
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| Synonyms |
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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. |
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| 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: 140 mg/mL (363.73 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 | 2.5981 mL | 12.9904 mL | 25.9808 mL | |
| 5 mM | 0.5196 mL | 2.5981 mL | 5.1962 mL | |
| 10 mM | 0.2598 mL | 1.2990 mL | 2.5981 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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