Soraprazan (BYK61359)
(Synonyms: BYK61359) 目录号 : GC30130
Soraprazan (BYK61359) (BYK61359) 是一种选择性的、可逆的 K 竞争性 H,K-ATPase 抑制剂 (Ki=6.4 nM)，在胃腺中的 IC50 为 0.19 μM。
Cas No.:261944-46-1
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
Kinase experiment: | [3H]Soraprazan binding studies are carried out at 20°C. In saturation experiments to determine the Kd value, ion-leaky gastric vesicles (0.01-0.02 mg/mL) are resuspended in a buffer composed of 20 mM Tris-HCl, pH 7.0, 2 mM MgCl2, and 2 mM ATP (pH 7.0 by Tris) in the presence of increasing concentrations of [3H]soraprazan (0.1 nM-1 μM). Nonspecific binding is determined in the presence of a 100 fold excess of unlabeled soraprazan over the concentration range of [3H]soraprazan used. The enzyme suspension (1 mL) is incubated at 20°C for 30 min and rapidly filtered through a nitrocellulose membrane filter (0.45 μM) prewet with a solution composed of 20 mM Tris-HCl, pH 7.0, 10% polyethylene glycol 3350 that is placed on top of a glass fiber filter. The membrane is ished five times with 2.5 mL of a buffer composed of 20 mM Tris-HCl, pH 7.0, and 10% polyethylene glycol 3350 to remove unbound inhibitor. The membrane is put into a 20-mL scintillation vial, dimethylacetamide (0.5 mL) is added to dissolve the membrane, and 14 mL of scintillation solvent is added and counted. Binding of [3H]soraprazan is determined by subtracting the nonspecific binding of [3H]soraprazan, obtained in the presence of the 100-fold excess of nonradioactive soraprazan, from the amounts of [3H]soraprazan bound to the membrane in the absence of the cold inhibitor. |
References: [1]. Simon WA, et al. Soraprazan: setting new standards in inhibition of gastric acid secretion. J Pharmacol Exp Ther. 2007 Jun;321(3):866-74. Epub 2007 Mar 16. | |
Soraprazan is a reversible, and fast-acting inhibitor of gastric H+/K+ ATPase.
Soraprazan is a potent inhibitor of gastric H,K-ATPase, with an IC50 of 0.1 μM when measured in ion-leaky vesicles in the presence of 1 mM potassium. Soraprazan also effectively inhibits dibutyryl cAMP-stimulated [14C]AP accumulation in isolated gastric glands with an IC50 of 0.19 μM (0.09-0.40 μM geometric mean from n=6 with 95% confidence limits). In ion-leaky vesicles, soraprazan is a potent k-competitive inhibitor of the H,K-ATPase, with Ki of 6.4 nM. Soraprazan binds to the H,K-ATPase in ion-leaky vesicles with a Kd of 26.4 nM and a Bmax of 2.89 nmol/mg[1].
[1]. Simon WA, et al. Soraprazan: setting new standards in inhibition of gastric acid secretion. J Pharmacol Exp Ther. 2007 Jun;321(3):866-74. Epub 2007 Mar 16.
| Cas No. | 261944-46-1 | SDF | |
| 别名 | BYK61359 | ||
| Canonical SMILES | O[C@@H]1[C@@H](C2=CC=CC=C2)NC3=C(C=CN4C3=NC(C)=C4C)[C@H]1OCCOC | ||
| 分子式 | C21H25N3O3 | 分子量 | 367.44 |
| 溶解度 | DMSO : ≥ 150 mg/mL (408.23 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 | 2.7215 mL | 13.6077 mL | 27.2153 mL |
| 5 mM | 0.5443 mL | 2.7215 mL | 5.4431 mL |
| 10 mM | 0.2722 mL | 1.3608 mL | 2.7215 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。
Medicinal Attributes of Imidazo[1,2-a]pyridine Derivatives: An Update
Curr Top Med Chem 2016;16(26):2963-2994.27150367 10.2174/1568026616666160506145539
The imidazo[1,2-a]pyridine scaffold is recognized as a privileged structure as it represents a promising area for identification of lead structures towards the discovery of new synthetic drug molecules. Several commercial drugs such as Zolpidem, Olprinone, Soraprazan and many other compounds in biological testing and preclinical evaluation, illustrate the wide therapeutic spectrum in this class of drug scaffolds. The present manuscript represents the assimilation of literature pertaining to medicinal aspects of this pharmacophore including the structure-activity relationships.
Structural Basis for Binding of Potassium-Competitive Acid Blockers to the Gastric Proton Pump
J Med Chem 2022 Jun 9;65(11):7843-7853.35604136 10.1021/acs.jmedchem.2c00338
As specific inhibitors of the gastric proton pump, responsible for gastric acidification, K+-competitive acid blockers (P-CABs) have recently been utilized in the clinical treatment of gastric acid-related diseases in Asia. However, as these compounds have been developed based on phenotypic screening, their detailed binding poses are unknown. We show crystal and cryo-EM structures of the gastric proton pump in complex with four different P-CABs, tegoprazan, Soraprazan, PF-03716556 and revaprazan, at resolutions reaching 2.8 Å. The structures describe molecular details of their interactions and are supported by functional analyses of mutations and molecular dynamics simulations. We reveal that revaprazan has a novel binding mode in which its tetrahydroisoquinoline moiety binds deep in the cation transport conduit. The mechanism of action of these P-CABs can now be evaluated at the molecular level, which will facilitate the rational development and improvement of currently available P-CABs to provide better treatment of acid-related gastrointestinal diseases.
Soraprazan: setting new standards in inhibition of gastric acid secretion
J Pharmacol Exp Ther 2007 Jun;321(3):866-74.17369284 10.1124/jpet.107.120428
After treatment of millions of patients suffering from gastroesophageal reflux disease (GERD) and other acid-related ailments with proton pump inhibitors, there are still unmet medical needs such as rapid and reliable pain relief, especially for nocturnal acid breakthrough. In this work, we introduce and characterize the biochemistry and pharmacology of the potassium-competitive acid blocker (P-CAB) Soraprazan, a novel, reversible, and fast-acting inhibitor of gastric H,K-ATPase. Inhibitory and binding properties of Soraprazan were analyzed together with its mode of action, its selectivity, and its in vivo potency. This P-CAB has an IC(50) of 0.1 microM if measured with ion leaky vesicles and of 0.19 microM in isolated gastric glands. With a K(i) of 6.4 nM, a K(d) of 26.4 nM, and a B(max) of 2.89 nmol/mg, this compound is a highly potent and reversible inhibitor of the H,K-ATPase. Soraprazan shows immediate inhibition of acid secretion in various in vitro models and in vivo and was found to be more than 2000-fold selective for H,K-ATPase over Na,K- and Ca-ATPases. Soraprazan is superior to esomeprazole in terms of onset of action and the extent and duration of pH elevation in vivo in the dog. Rapid and consistent inhibition of acid secretion by Soraprazan renders the P-CABs a promising group of compounds for therapy of GERD.
Remofuscin induces xenobiotic detoxification via a lysosome-to-nucleus signaling pathway to extend the Caenorhabditis elegans lifespan
Sci Rep 2022 May 3;12(1):7161.35504961 PMC9064964
Lipofuscin is a representative biomarker of aging that is generated naturally over time. Remofuscin (Soraprazan) improves age-related eye diseases by removing lipofuscin from retinal pigment epithelium (RPE) cells. In this study, the effect of remofuscin on longevity in Caenorhabditis elegans and the underlying mechanism were investigated. The results showed that remofuscin significantly (p < 0.05) extended the lifespan of C. elegans (N2) compared with the negative control. Aging biomarkers were improved in remofuscin-treated worms. The expression levels of genes related to lysosomes (lipl-1 and lbp-8), a nuclear hormone receptor (nhr-234), fatty acid beta-oxidation (ech-9), and xenobiotic detoxification (cyp-34A1, cyp-35A1, cyp-35A2, cyp-35A3, cyp-35A4, cyp-35A5, cyp-35C1, gst-28, and gst-5) were increased in remofuscin-treated worms. Moreover, remofuscin failed to extend the lives of C. elegans with loss-of-function mutations (lipl-1, lbp-8, nhr-234, nhr-49, nhr-8, cyp-35A1, cyp-35A2, cyp-35A3, cyp-35A5, and gst-5), suggesting that these genes are associated with lifespan extension in remofuscin-treated C. elegans. In conclusion, remofuscin activates the lysosome-to-nucleus pathway in C. elegans, thereby increasing the expression levels of xenobiotic detoxification genes resulted in extending their lifespan.
Penetration, distribution, and elimination of remofuscin/Soraprazan in Stargardt mouse eyes following a single intravitreal injection using pharmacokinetics and transmission electron microscopic autoradiography: Implication for the local treatment of Stargardt's disease and dry age-related macular degeneration
Pharmacol Res Perspect 2020 Dec;8(6):e00683.33164337 PMC7649431
Age-related macular degeneration (AMD) is the leading cause of blindness in older people in the developed world while Stargardt's disease (SD) is a juvenile macular degeneration and an orphan disease. Both diseases are untreatable and are marked by accumulation of lipofuscin advancing to progressive deterioration of the retinal pigment epithelium (RPE) and retina and subsequent vision loss till blindness. We discovered that a small molecule belonging to the tetrahydropyridoether class of compounds, Soraprazan renamed remofuscin, is able to remove existing lipofuscin from the RPE. This study investigated the drug penetration, distribution, and elimination into the eyes of a mouse model for increased lipofuscinogenesis, following a single intravitreal injection. We measured the time course of concentrations of remofuscin in different eye tissues using high-performance liquid chromatography combined with mass spectroscopy (HPLC-MS). We also visualized the penetration and distribution of 3 H-remofuscin in eye sections up to 20 weeks post-injection using transmission electron microscopic (TEM) autoradiography. The distribution of silver grains revealed that remofuscin accumulated specifically in the RPE by binding to the RPE pigments (melanin, lipofuscin and melanolipofuscin) and that it was still detected after 20 weeks. Importantly, the melanosomes in choroidal melanocytes only rarely bind remofuscin emphasizing its potential to serve as an active ingredient in the RPE for the treatment of SD and dry AMD. In addition, our study highlights the importance of electron microscopic autoradiography as it is the only method able to show drug binding with a high intracellular resolution.