Diabetes Panel
Eurofins Discovery의 Diabetes 분석 서비스는 인슐린 분비 및 감수성과
관련된 다양한 대사 표적에 대한 약물의 기능적 활성을 평가할 수 있는 서비스를 제공하고 있습니다.
서비스를 소개합니다
Diabetes Panel
Eurofins Discovery는 Diabetes 관련하여 인슐린 분비와 연관된 Insulin Release Panel (PP277), 인슐린
감수성과 연관된 Insulin Sensitivity Panel (PP278) 두가지 Panel 서비스를 제공하고 있습니다. 두 Panel에는 인슐린 분비및 저항성과의 연관성이 알려진 17개의 치료
타깃이 포함되어 있으며, 약물 후보물질의 작용 메커니즘(MOA)과
다중 표적 효과를 이해하는 데 도움을 줍니다.
Insulin Release Panel: GLP1R, GCK, IBAT, SGLT1 등 10개의 Target-based assay와 1개의 Phenotypic insulin release assay가 포함되어, 후보 약물의 인슐린 분비를 자극 관련 활성을 평가합니다.
Class | Target | Item# | Biological Relevance |
|---|---|---|---|
GPCR | GLP1R | 231710 | GLP1R activation increases insulin secretion in a glucose-dependent manner and reduces glycaemia by inhibiting glucagon secretion. |
GIPR | 312970-0 | The combination of GLP1 and GIP analogues improves glycaemic control and weight loss. Chimeric peptides that mimic GIP and GLP1 have been developed for diabetes treatment. | |
GPR40 | 311810-0 | PR40 activation stimulates intestinal secretion of GLP1 and GIP with pancreatic secretion of insulin in a glucose-dependent manner. | |
NPY1R | 257010 | NPY1R activation may particularly contribute to insulin secretion after weight loss surgery for T2D. The analogues of PYY(1-36), a selective NPY1R agonist, have been designed for diabetes treatment. | |
GCGR | 231680 | GCGR antagonists that inhibit glucagon actions can counter high glycaemia in diabetes. Several GLP1R/GCGR dual agonists and GLP1R/GCGR/GIPR tri-agonists have been developed for diabetes treatment. | |
Kinase | GCK | 199101-0 | GCK activation promotes hepatic glucose uptake, glycogen synthesis, and enhances glucose-stimulated insulin secretion from the pancreas. |
Peptidase | DPP4 | 199007 | DPP4 plays a key role in the clearance of GLP1. DPP4 inhibition has been well-established for glycaemic control improvement in T2D patients. |
Ion Channel | KATP | 265600 | Inhibition of pancreatic KATP channels leads to depolarization and increases intracellular calcium levels, resulting in insulin release. |
Transporter | IBAT | 314100-1 | IBAT inhibition prevents bile acid reabsorption, which leads to GLP1 secretion and GLP1R activation. |
SGLT1 | 355710-1 | SGLT1 inhibition delays glucose absorption in the small intestine and colon, resulting in glucose reduction, insulin secretion, and glycaemic control improvement. | |
Phenotypic | Insulin Release | 331500-0 | Pancreatic islet beta cell line HIT-T15 is used to assess the ability to stimulate insulin release by test compounds. |
Insulin Sensitivity Panel: AMPK, 11β-HSD1, SIRT1, PPARγ 등 7개의 Target-based assay를 통하여 약물의 인슐린 저항성 관련 활성을 평가합니다.
Class | Target | Item# | Biological Relevance |
|---|---|---|---|
Kinase | AMPK | 199100-0 | AMPK is the center of energy metabolism that regulates glucose uptake, glucose, and lipid metabolism. The first line antidiabetic drug metformin, which is an indirect AMPK activator, is widely prescribed for T2D patients. |
INSR | 243000 | INSR activation causes the translocation of GLUT4 to the cellular membrane. This enhances glucose uptake and metabolism. Abnormally expressed INSR is highly associated with insulin resistance. | |
GSK3β | 176500 | GSK3β inhibition enhances glycogenesis and glucose metabolism. GSK3β signaling pathway is highly correlated with diabetes complications such as diabetic neuropathy. | |
NHR | PPARγ | 267500 | PPARγ activation improves insulin sensitivity by increasing glucose uptake through GLUT4 in muscle and reducing free fatty acid by lipogenesis. This enhances the utilization of glucose. |
Phosphatase | PTP1B | 192010 | PTP1B Inhibition suppresses activated INSR and Leptin receptors, leading to insulin sensitivity improvement. |
Deacetylase | SIRT1 | 199102-0 | SIRT1 activation inhibits PTP1B activity and thus increases insulin sensitivity. SIRT1 activation also enhances insulin secretion. |
Dehydrogenase | 11β-HSD1 | 125710 | Abnormal high cortisol level is highly associated with insulin resistance and diabetes. 11β-HSD1 catalyzes the conversion of cortisone to cortisol. 11β-HSD1 inhibition reduces cortisol level and results in insulin sensitivity improvement. |
이런 서비스 유형을 제공합니다
서비스 유형 | Insulin Release LeadHunter Panel | Insulin Sensitivity LeadHunter Panel |
|---|---|---|
Assay 수 | 11 | 7 |
실험농도 | 선택 가능 | |
(Top Concentration) | 선택 가능 | |
농도 개수 | 선택 가능 | |
반복실험횟수 | Duplicate | |
Sample Volume | 350 μL of a 10 mM stock or 2 mg pre-weighed powder (assuming FW≦500 and purity 100%) | 50 μL of 10 mM stock or 1 mg (pre-weighed) powder (assuming FW≦500 and purity 100%) |
TAT | 20 Business Days | 15 Business Days |
서비스 장소 | Panlabs, Taiwan | |
데이터 자료를 살펴보세요
Figure 1. Pathology of T2D. Insulin is a hormone synthesized by β-cells of pancreatic islets, playing a key role in glucose homeostasis by reducing blood glucose levels. Insulin activates insulin receptors (INSR) in the liver, skeletal muscle, and adipose tissue to stimulate glucose transporter (GLUT4) translocating from the intracellular site to the cell membrane, making the cells efficiently uptake glucose. β-cell dysfunction follows damage from elevated free fatty acid (FFA) levels, obesity, insulin resistance, and inflammation. β-cells can compensate by promoting insulin release initially; however, as time passes, the compensatory mechanism declines, and β-cell mass decreases. The loss of β-cell mass is due to cell degranulation, causing increased α-cell glucagon and decreased β-cell insulin. Meanwhile, skeletal muscle and adipocytes are incapable of modulating the increased glucose levels. In addition, overloaded adipocytes increase lipolysis and cytokine release of inflammatory mediators such as TNF-α. Released FFAs also stimulate glycogenolysis in the liver. T2D is ultimately caused by a hyperglycaemia environment. Figure 1 is modified from Riddy DM, et al, 2018.
Figure 2. Demonstrated results for the Insulin Release Panel. A. Enzymatic GCK activation assay (#199101-0). GCK is a promising therapeutic target in which several clinical candidates are under clinical development for diabetes indication. The EC50 of the two reported GCK activators were validated via enzymatic GCK activation assay. PF-04991532 and Dorzagliatin are clinical candidates for T2D treatment in Phases 2 and 3, respectively.12,13 B. Cell-based SGLT1 inhibition assay (#355710-1). SGLT1 inhibition is an emerging antidiabetic strategy by reducing dietary glucose absorption in the intestine and increasing the release of gastrointestinal incretins like GLP-1.14 The IC50 of the approved antidiabetic agent was validated through the image-based SGLT1 uptake assay. Sotagliflozin (Zynquista™), the first-in-class dual inhibitor of SGLT1/2, was approved by EMA for T1D indication in 2019.15 Canagliflozin and Dapagliflozin, the selective SGLT2 inhibitors, are antidiabetic agents approved by FDA in 2013 and 2014, respectively.16 C. Representative images for SGLT1 inhibition assay. Uptake of the fluorescent substrate, 1-NBDG (160 µM), was performed by stably-expressed human SGLT1 cells (Control) and was significantly inhibited in the presence of Sotagliflozin (300 nM), Dapagliflozin (3 µM), or Canagliflozin (1 µM). The substrate uptake level was analyzed via high-content imaging
Figure 3. Demonstrative data of the Insulin Release Panel (A.) and the Insulin Sensitivity Panel (B.). A. Reported clinical candidates, PF-04991532 and dorzagliatin, were validated through the enzymatic GCK activation assay. B. Reported 11β-HSD1 inhibitors, PF-915275 and BVT-2733, were validated by the enzymatic 11β-HSD1 inhibition assay.
Figure 4. Therapeutic targets are included in the in vitro diabetes panels and in vitro NASH panels.
이런 분들에게 적극 추천합니다
타깃과 후보 약물의 상호작용을 이해하고 싶어요
이OO l A 연구기관
글로벌 CRO사와 긴밀한 Partnership과 오랜 경험과 축적된 노하우로 높은 품질의 결과를 제공해드립니다.
여러 Diabetes 타깃에 대한 패널 Assays가 필요해요
김OO l N제약회사
신뢰성과 전문성을 바탕으로 체계적이고 효율적으로 맞춤형 CRO 서비스를 제공해드립니다.
Diabetes 치료제로서의 가능성을 확인하고 싶어요
손OO l H대학교
Diabetes Panel은 비만 관련하여 주요 기전이 알려진 타깃들과 후보 약물의 상호작용을 확인하실 수 있습니다.
여러 Diabetes 타깃에 화합물 스크리닝을 빠르게 하고 싶어
손OO l B바이오테크
Diabetes Panel 두가지를 통하여 15 영업일 만에 17개의 실험 데이터 확보 했어요.
서비스는 이런 절차로 진행됩니다
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유선 및 방문상담
서비스상담
실험항목 및 조건 논의 -
최초 견적서 전달
계약
실험의뢰서(CSF) 작성
(필요시) 계약서 작성 -
실험 물질 전달
시료 준비
(택배 혹은 방문수령) -
매주 FedEx 발송
시료 발송
Tracking no. 안내
Report due date 안내 -
실험종료 안내
결과제공
최종 보고서 전달
결과 검토 및 상담
결제 진행
![[Flyer] Diabetes Drug Discovery](/upload/reference/cd98f00b2022812.jpg "[Flyer] Diabetes Drug Discovery")
![[White Paper] Diabetes Drug Discovery Utilizing in vitro panels and in vivo animal models to evaluate diabetes drug candidates](/upload/reference/cd98f00b2033911.jpg "[White Paper] Diabetes Drug Discovery Utilizing in vitro panels and in vivo animal models to evaluate diabetes drug candidates")