Corin
目录号 : GC34165
Corin是组氨酸赖氨酸特异性去甲基化酶(LSD1)和组氨酸脱乙酰化酶(HDAC)的双重抑制剂，其对LSD1的Ki(inact)值为110nM，对HDAC1的IC50值为147nM。
Cas No.:1808113-09-8
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Corin is a dual inhibitor of histone lysine specific demethylase (LSD1) and histone deacetylase (HDAC), with a Ki(inact) of 110 nM for LSD1 and an IC50 of 147 nM for HDAC1.
Corin is able to inhibit the deacetylation of semisynthetic, reconstituted nucleosomes by the CoREST ternary complex. Corin shows irreversible inhibition of HDAC1 activity. In Comparison to MS-275, corin appears to more potently (Corin EC50 95 nM vs. MS-275 EC50 420 nM) and efficaciously induce cellular H3K9 acetylation. Interestingly, Corin (1 μM) is non-toxic to primary human melanocytes in contrast to MS-275 (1 μM)[1].
[1]. Kalin JH, et al. Targeting the CoREST complex with dual histone deacetylase and demethylase inhibitors. Nat Commun. 2018 Jan 4;9(1):53.
| Cas No. | 1808113-09-8 | SDF | |
| Canonical SMILES | O=C(NC1=CC=C([C@H]2[C@H](N)C2)C=C1)CCCC3=CC=C(C(NC4=CC=CC=C4N)=O)C=C3 | ||
| 分子式 | C26H28N4O2 | 分子量 | 428.53 |
| 溶解度 | DMSO : 100 mg/mL (233.36 mM);Water : < 0.1 mg/mL (insoluble) | 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。 |
||
| 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 2.3336 mL | 11.6678 mL | 23.3356 mL |
| 5 mM | 0.4667 mL | 2.3336 mL | 4.6671 mL |
| 10 mM | 0.2334 mL | 1.1668 mL | 2.3336 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。
Corin protects H2O2-induced apoptosis through PI3K/AKT and NF-κB pathway in cardiomyocytes
Biomed Pharmacother 2018 Jan;97:594-599.PMID:29101802DOI:10.1016/j.biopha.2017.10.090.
Background: The functional role of Corin in H2O2-induced apoptosis is largely unexplored. The present study investigated the protective role of Corin against cell injury by possible involvement of PI3K/AKT and NF-kB signaling pathways in cardiomyocytes. Method: Cardiomyocytes H9c2 and HL-1 cells were used in the study. Cell viability was measured using CCK-8 assay; cell apoptosis was analyzed by flow cytometry, TUNEL assay, and western blot; and cell migration was measured using wound healing assay. The fluorescent intensities of reactive oxygen species (ROS) were measured using a flow cytometer. Quantitative RT-PCR was used to measure the mRNA expression of Corin. Western blot was used to measure the protein expression of Corin, apoptosis-related proteins (Bax, cleaved-Caspase-3 and -9), and PI3K/AKT and NF-κB signaling pathway proteins. Results: Treatment with H2O2 (150μM, 6h) significantly decreased cell viability and relative migration, increased apoptosis, and decreased the expression of Corin in H9c2 and HL-1 cells. Overexpression of Corin alleviated the H2O2-induced cell injury by increasing cell viability and migration and decreasing apoptosis in the cardiomyocytes. Overexpression of Corin also decreased the ROS level in the cardiomyocytes likely through upregulating HIF-1α. These effects of Corin on the cell injury might be mediated via the corin-induced activations of PI3K/AKT and NF-κB signaling pathways. Conclusion: Overexpression of Corin protected cardiomyocytes from H2O2-induced injury by decreasing apoptosis and ROS level via activations of the PI3K/AKT and NF-κB signaling pathways and upregulating HIF-1α.
Function and regulation of Corin in physiology and disease
Biochem Soc Trans 2020 Oct 30;48(5):1905-1916.PMID:33125488DOI:10.1042/BST20190760.
Atrial natriuretic peptide (ANP) is of major importance in the maintenance of electrolyte balance and normal blood pressure. Reduced plasma ANP levels are associated with the increased risk of cardiovascular disease. Corin is a type II transmembrane serine protease that converts the ANP precursor to mature ANP. Corin deficiency prevents ANP generation and alters electrolyte and body fluid homeostasis. Corin is synthesized as a zymogen that is proteolytically activated on the cell surface. Factors that disrupt Corin folding, intracellular trafficking, cell surface expression, and zymogen activation are expected to impair Corin function. To date, Corin variants that reduce Corin activity have been identified in hypertensive patients. In addition to the heart, Corin expression has been detected in non-cardiac tissues, where Corin and ANP participate in diverse physiological processes. In this review, we summarize the current knowledge in Corin biosynthesis and post-translational modifications. We also discuss tissue-specific Corin expression and function in physiology and disease.
Corin: A Key Mediator in Sodium Homeostasis, Vascular Remodeling, and Heart Failure
Biology (Basel) 2022 May 7;11(5):717.PMID:35625445DOI:10.3390/biology11050717.
Atrial natriuretic peptide (ANP) is a crucial element of the cardiac endocrine function that promotes natriuresis, diuresis, and vasodilation, thereby protecting normal blood pressure and cardiac function. Corin is a type II transmembrane serine protease that is highly expressed in the heart, where it converts the ANP precursor to mature ANP. Corin deficiency prevents ANP activation and causes hypertension and heart disease. In addition to the heart, Corin is expressed in other tissues, including those of the kidney, skin, and uterus, where corin-mediated ANP production and signaling act locally to promote sodium excretion and vascular remodeling. These results indicate that Corin and ANP function in many tissues via endocrine and autocrine mechanisms. In heart failure patients, impaired natriuretic peptide processing is a common pathological mechanism that contributes to sodium and body fluid retention. In this review, we discuss most recent findings regarding the role of Corin in non-cardiac tissues, including the kidney and skin, in regulating sodium homeostasis and body fluid excretion. Moreover, we describe the molecular mechanisms underlying Corin and ANP function in supporting orderly cellular events in uterine spiral artery remodeling. Finally, we assess the potential of corin-based approaches to enhance natriuretic peptide production and activity as a treatment of heart failure.
Role of Corin in the regulation of blood pressure
Curr Opin Nephrol Hypertens 2017 Mar;26(2):67-73.PMID:27898523DOI:10.1097/MNH.0000000000000297.
Purpose of review: Corin is a transmembrane protease that activates atrial natriuretic peptide (ANP), an important hormone in regulating salt-water balance and blood pressure. This review focuses on the regulation of Corin function and potential roles of Corin defects in hypertensive, heart, and renal diseases. Recent findings: Proprotein convertase subtilisin/kexin-6 has been identified as a primary enzyme that converts zymogen Corin to an active protease. Genetic variants that impair Corin intracellular trafficking, cell surface expression, and zymogen activation have been found in patients with hypertension, cardiac hypertrophy, and pre-eclampsia. Reduced Corin expression has been detected in animal models of cardiomyopathies and in human failing hearts. Low levels of circulating soluble Corin have been reported in patients with heart disease and stroke. Corin, ANP and natriuretic peptide receptor-A mRNAs, and proteins have been colocalized in human renal segments, suggesting a corin-ANP autocrine function in the kidney. Summary: Corin is a key enzyme in the natriuretic peptide system. The latest findings indicate that corin-mediated ANP production may act in a tissue-specific manner to regulate cardiovascular and renal function. Corin defects may contribute to major diseases such as hypertension, heart failure, pre-eclampsia, and kidney disease.
Corin in clinical laboratory diagnostics
Clin Chim Acta 2012 Feb 18;413(3-4):378-83.PMID:22093942DOI:10.1016/j.cca.2011.10.032.
Corin is a transmembrane serine protease identified in the heart, where it converts natriuretic peptides from inactive precursors to mature active forms. Studies in animal models and patients with hypertension and heart disease demonstrate that Corin is critical in maintaining normal blood pressure and cardiac function. Like many proteolytic enzymes, Corin expression and activity are regulated. Cell biology experiments indicate that transcriptional control, intracellular protein trafficking, cell surface targeting, zymogen activation and ectodomain shedding are important mechanisms in regulating Corin expression and activity in the heart. More recently, soluble Corin was detected in human blood and its levels were found to be reduced in patients with heart failure (HF). These findings indicate that Corin deficiency may be involved in the pathogenesis of HF and suggest that soluble Corin may be used as a biomarker for the disease. In this review, we describe the function and regulation of Corin and discuss recent studies of soluble Corin in human blood and its potential use as a biomarker for HF.