Glycerol phenylbutyrate
(Synonyms: 苯丁酸甘油酯,HPN-100) 目录号 : GC36161
Glycerol phenylbutyrate (GT4P, HPN-100M, Ravicti) is a nitrogen-binding agent and acts as a sigma-2 (σ2) receptor ligand with a pKi of 8.02. Glycerol phenylbutyrate is a prodrug in which phenylbutyrate (PBA) is released from the glycerol backbone by lipases in the gastrointestinal tract.
Cas No.:611168-24-2
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Glycerol phenylbutyrate (GT4P, HPN-100M, Ravicti) is a nitrogen-binding agent and acts as a sigma-2 (σ2) receptor ligand with a pKi of 8.02. Glycerol phenylbutyrate is a prodrug in which phenylbutyrate (PBA) is released from the glycerol backbone by lipases in the gastrointestinal tract.
[1] Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2017 Apr. [2] Antonio Rescifina, et al.Eur J Pharm Sci. 2017 Aug 30;106:94-101.
| Cas No. | 611168-24-2 | SDF | |
| 别名 | 苯丁酸甘油酯,HPN-100 | ||
| Canonical SMILES | O=C(CCCC1=CC=CC=C1)OC(COC(CCCC2=CC=CC=C2)=O)COC(CCCC3=CC=CC=C3)=O | ||
| 分子式 | C33H38O6 | 分子量 | 530.65 |
| 溶解度 | DMSO: ≥ 150 mg/mL (282.67 mM); Ethanol: 50 mg/mL (94.22 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.8845 mL | 9.4224 mL | 18.8448 mL |
| 5 mM | 0.3769 mL | 1.8845 mL | 3.769 mL |
| 10 mM | 0.1884 mL | 0.9422 mL | 1.8845 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Suggested guidelines for the diagnosis and management of urea cycle disorders: First revision
J Inherit Metab Dis 2019 Nov;42(6):1192-1230.PMID:30982989DOI:10.1002/jimd.12100.
In 2012, we published guidelines summarizing and evaluating late 2011 evidence for diagnosis and therapy of urea cycle disorders (UCDs). With 1:35 000 estimated incidence, UCDs cause hyperammonemia of neonatal (~50%) or late onset that can lead to intellectual disability or death, even while effective therapies do exist. In the 7 years that have elapsed since the first guideline was published, abundant novel information has accumulated, experience on newborn screening for some UCDs has widened, a novel hyperammonemia-causing genetic disorder has been reported, Glycerol phenylbutyrate has been introduced as a treatment, and novel promising therapeutic avenues (including gene therapy) have been opened. Several factors including the impact of the first edition of these guidelines (frequently read and quoted) may have increased awareness among health professionals and patient families. However, under-recognition and delayed diagnosis of UCDs still appear widespread. It was therefore necessary to revise the original guidelines to ensure an up-to-date frame of reference for professionals and patients as well as for awareness campaigns. This was accomplished by keeping the original spirit of providing a trans-European consensus based on robust evidence (scored with GRADE methodology), involving professionals on UCDs from nine countries in preparing this consensus. We believe this revised guideline, which has been reviewed by several societies that are involved in the management of UCDs, will have a positive impact on the outcomes of patients by establishing common standards, and spreading and harmonizing good practices. It may also promote the identification of knowledge voids to be filled by future research.
Covert and Overt Hepatic Encephalopathy: Diagnosis and Management
Clin Gastroenterol Hepatol 2015 Nov;13(12):2048-61.PMID:26164219DOI:10.1016/j.cgh.2015.06.039.
Hepatic encephalopathy (HE) is part of a spectrum of neurocognitive changes in cirrhosis. HE is divided into 2 broad categories based on severity: covert hepatic encephalopathy (CHE) and overt hepatic encephalopathy (OHE). CHE has a significant impact on a patient's quality of life, driving performance, and recently has been associated with increased hospitalizations and death. Likewise, OHE is associated with increased rates of hospitalizations and mortality, and poor quality of life. Given its significant burden on patients, care takers, and the health care system, early diagnosis and management are imperative. In addition, focus also should be directed on patient and family member education on the disease progression and adherence to medications. Treatment strategies include the use of nonabsorbable disaccharides, antibiotics (ie, rifaximin), and, potentially, probiotics. Other therapies currently under further investigation include L-ornithine-L-aspartate, ornithine phenylacetate, Glycerol phenylbutyrate, molecular adsorbent recirculating system, and albumin infusion.
Switching to Glycerol phenylbutyrate in 48 Patients with Urea Cycle Disorders: Clinical Experience in Spain
J Clin Med 2022 Aug 28;11(17):5045.PMID:36078975DOI:10.3390/jcm11175045.
Background and objectives: Glycerol phenylbutyrate (GPB) has demonstrated safety and efficacy in patients with urea cycle disorders (UCDs) by means of its clinical trial program, but there are limited data in clinical practice. In order to analyze the efficacy and safety of GPB in clinical practice, here we present a national Spanish experience after direct switching from another nitrogen scavenger to GPB. Methods: This observational, retrospective, multicenter study was performed in 48 UCD patients (age 11.7 ± 8.2 years) switching to GPB in 13 centers from nine Spanish regions. Clinical, biochemical, and nutritional data were collected at three different times: prior to GPB introduction, at first follow-up assessment, and after one year of GPB treatment. Number of related adverse effects and hyperammonemic crisis 12 months before and after GPB introduction were recorded. Results: GPB was administered at a 247.8 ± 102.1 mg/kg/day dose, compared to 262.6 ± 126.1 mg/kg/day of previous scavenger (46/48 Na-phenylbutyrate). At first follow-up (79 ± 59 days), a statistically significant reduction in ammonia (from 40.2 ± 17.3 to 32.6 ± 13.9 μmol/L, p < 0.001) and glutamine levels (from 791.4 ± 289.8 to 648.6 ± 247.41 μmol/L, p < 0.001) was observed. After one year of GPB treatment (411 ± 92 days), we observed an improved metabolic control (maintenance of ammonia and glutamine reduction, with improved branched chain amino acids profile), and a reduction in hyperammonemic crisis rate (from 0.3 ± 0.7 to less than 0.1 ± 0.3 crisis/patients/year, p = 0.02) and related adverse effects (RAE, from 0.5 to less than 0.1 RAEs/patients/year p < 0.001). Conclusions: This study demonstrates the safety of direct switching from other nitrogen scavengers to GPB in clinical practice, which improves efficacy, metabolic control, and RAE compared to previous treatments.
Glycerol phenylbutyrate efficacy and safety from an open label study in pediatric patients under 2 months of age with urea cycle disorders
Mol Genet Metab 2021 Jan;132(1):19-26.PMID:33388234DOI:10.1016/j.ymgme.2020.12.002.
Background/aims: Neonatal onset Urea cycle disorders (UCDs) can be life threatening with severe hyperammonemia and poor neurological outcomes. Glycerol phenylbutyrate (GPB) is safe and effective in reducing ammonia levels in patients with UCD above 2 months of age. This study assesses safety, ammonia control and pharmacokinetics (PK) of GPB in UCD patients below 2 months of age. Methods: This was an open-label study in UCD patients aged 0 - 2 months, consisting of an initiation/transition period (1 - 4 days) to GPB, followed by a safety extension period (6 months to 2 years). Patients presenting with a hyperammonemic crisis (HAC) did not initiate GPB until blood ammonia levels decreased to below 100 µmol/L while receiving sodium phenylacetate/sodium benzoate and/or hemodialysis. Ammonia levels, PK analytes and safety were evaluated during transition and monthly during the safety extension for 6 months and every 3 months thereafter. Results: All 16 patients with UCD (median age 0.48 months, range 0.1 to 2.0 months) successfully transitioned to GPB within 3 days. Average plasma ammonia level excluding HAC was 94.3 µmol/L at baseline and 50.4 µmol/L at the end of the transition period (p = 0.21). No patient had a HAC during the transition period. During the safety extension, the majority of patients had controlled ammonia levels, with mean plasma ammonia levels lower during GPB treatment than baseline. Mean glutamine levels remained within normal limits throughout the study. PK analyses indicate that UCD patients <2 months are able to hydrolyze GPB with subsequent absorption of phenylbutyric acid (PBA), metabolism to phenylacetic acid (PAA) and conjugation with glutamine. Plasma concentrations of PBA, PAA, and phenylacetylglutamine (PAGN) were stable during the safety extension phase and mean plasma phenylacetic acid: phenylacetylglutamine ratio remained below 2.5 suggesting no accumulation of GPB. All patients reported at least 1 treatment emergent adverse event with gastroesophageal reflux disease, vomiting, hyperammonemia, diaper dermatitis (37.5% each), diarrhea, upper respiratory tract infection and rash (31.3% each) being the most frequently reported. Conclusions: This study supports safety and efficacy of GPB in UCD patients aged 0 -2 months who cannot be managed by dietary protein restriction and/or amino acid supplementation alone. GPB undergoes intestinal hydrolysis with no accumulation in this population.
Glycerol phenylbutyrate for the chronic management of urea cycle disorders
Expert Rev Endocrinol Metab 2014 Sep;9(5):427-434.PMID:30736206DOI:10.1586/17446651.2014.945908.
Glycerol phenylbutyrate (GPB) is a new generation ammonia scavenger drug that was recently approved by the US FDA for chronic management in patients with urea cycle defect disorders after multicenter clinical trials. GPB is composed of three molecules of phenylbutyrate (PB) that are esterified to a glycerol backbone. The active agent, phenylacetate, is generated through multiple metabolic steps including hydrolysis in the small intestine by pancreatic triglyceride lipases. Its pharmacokinetic pattern is characterized by a slower release of the active metabolite than unconjugated PB, which contributes to superior ammonia control and fewer episodes of hyperammonemia. GPB is well tolerated with fewer gastrointestinal complications compared with sodium benzoate or PB. These unique features suggest that it may enhance adherence and, potentially, in improved outcomes in urea cycle disorder patients. GPB may have therapeutic potential in additional conditions such as chronic hepatic encephalopathy or other inherited metabolic disorders.