141758-74-9 Usage
Description
Exendin-4, also known as exenatide, is an incretin mimetic peptide composed of 39 amino acids. It is an analog of glucagon-like peptide 1 (GLP-1) and functions as an insulinotropic agent with a long half-life. Historically, Exendin-4 was isolated from the venom of the Gila monster lizard, Heloderma suspectum. It is a high-affinity GLP-1 receptor agonist, potently inducing cAMP formation without stimulating amylase release in pancreatic acini. Exendin-4 also protects against glutamate-induced neurotoxicity and has been used in various applications due to its unique properties.
Uses
Used in Pharmaceutical Industry:
Exendin-4 is used as an incretin mimetic for the treatment of type 2 diabetes. It acts as an adjunctive therapy to improve glycemic control in patients who are taking metformin, a sulfonylurea, or both, but have not achieved adequate glycemic control. Exendin-4 potentiates glucose-stimulated insulin secretion and moderates peak serum glucagon levels during hyperglycemic periods following meals, without interfering with glucagon release in response to hypoglycemia.
Used in Research Applications:
Exendin-4 is used as a research tool in HepG2 cells to study its effects on the GLP-1 receptor and to exclude the influence of auxiliary material. It has also been used as an r(GLP-1R) agonist to investigate its role in various biological processes and to understand its potential applications in different fields.
Used in Anticancer Applications:
Although not explicitly mentioned in the provided materials, Exendin-4 has shown potential in cancer research due to its ability to modulate several oncological signaling pathways. It may be used as an anticancer agent in the future, particularly against solid malignancies, by enhancing chemo-sensitivity and efficacy in resistant cases.
Used in Drug Delivery Systems:
Exendin-4 can be incorporated into novel drug delivery systems to enhance its applications and efficacy against various diseases, including diabetes and potentially cancer. These systems may involve the use of organic and metallic nanoparticles as carriers for Exendin-4 delivery, aiming to improve its delivery, bioavailability, and therapeutic outcomes.
Brand Name:
Exendin-4 is commercially available under the brand name Byetta, which is administered as a subcutaneous injection within an hour before morning and evening meals. The dosing regimen for exenatide is 5 or 10 mg twice daily. The most common adverse events reported with exenatide include nausea, vomiting, diarrhea, feeling jittery, dizziness, headache, and dyspepsia.
New diabetes drugs
Diabetes is a metabolic disorder characterized by chronic hyperglycemia caused by a variety of causes , high blood sugar is caused by insulin secretion or its effect defect. Diabetes can be divided into type 1 diabetes, type 2 diabetes, other specific types of diabetes, and gestational diabetes, among which type 2 diabetes account for more than 90%.
Exendin-4 is a new diabetes drug successfully developed by American Eli Lilly Company it belongs to incretin analogues, it is the first member of the incretin analogues family , it is the synthetic peptide compound, which can simulate physiological behavior of the natural state secretion of GLP-1 in vivo ,it is similar to human pancreatic glucagon-like peptide effect-1 (GLP-1),it can promote glucose-dependent insulin secretion, it has inhibition effect of inappropriate glucose-dependent glucagon secretion, slowing gastric emptying, it improves the sensitivity of peripheral tissues to insulin, and it makes blood sugar adequately controlled. Clinically it is used for the treatment of type Ⅱ diabetes patients whose blood sugar is unbale to be controlled by metformin, sulfonylurea, or combination of metformin and sulfonylurea.
From April 28, 2005 to October 29, 2008, the US Food and Drug Administration (abbreviation: FDA) Adverse Event Reporting System had received reports of 78 cases of patients with renal exenatide change. In the meantime, the United States had made a total of more than 6.6 million Exendin-4 prescription, therefore, FDA thought the received 78 cases was in a small proportion of the proportion of all patients reporting use of the drug. Currently FDA has completed an assessment of these reported cases, including 62 cases of acute renal failure cases and 16 cases of renal insufficiency cases. Acute renal failure or renal dysfunction occurs three days to two years after treatment. The age span is 23 years to 83 years, mean age is 60 years.
The above information is edited by the lookchem of Tian Ye.
Originator
Amylin (US)
Biochem/physiol Actions
Activates GLP-1 (glucagon-like peptide-1) receptors to increase intracellular cAMP in pancreatic acinar cells; has no effect on VIP receptors.
in vitro
exendin-4 showed a pronounced effect on intracellular camp generation. treatment of glp-1 in combination with exendin-4 showed additive action on the generation of camp. in isolated rat islets and in mouse insulinoma beta tc-1 cells, exendin-4 stimulated the glucose-induced insulin secretion in a dose dependent manner [2]. in basal forebrain cholinergic neurons, exendin-4 greatly reduced ibotenic acid-induced depletion of choline acetyltransferase immunoreactivity [3].
in vivo
in ob/ob mice, administration of exendin-4 (10 μg/kg or 20 μg/kg) improved insulin sensitivity and significantly reduced serum glucose and hepatic steatosis. exendin-4 appeared to effectively reverse hepatic steatosis in ob/ob mice by improving insulin sensitivity [1]. in athymic mice, 63% of exendin-4-treated mice achieved graft function compared with 21% of untreated mice (p = 0.033) in the short-term study. 88% of treated mice had functioning grafts compared with 22% of controls (p = 0.015) in the long-term study. exendin-4-treated mice gained significantly more weight than the untreated counterparts [4].
references
ding x, saxena n k, lin s, et al. exendin‐4, a glucagon‐like protein‐1 (glp‐1) receptor agonist, reverses hepatic steatosis in ob/ob mice[j]. hepatology, 2006, 43(1): 173-181.gke r, fehmann h c, linn t, et al. exendin-4 is a high potency agonist and truncated exendin-(9-39)-amide an antagonist at the glucagon-like peptide 1-(7-36)-amide receptor of insulin-secreting beta-cells[j]. journal of biological chemistry, 1993, 268(26): 19650-19655.perry t a, haughey n j, mattson m p, et al. protection and reversal of excitotoxic neuronal damage by glucagon-like peptide-1 and exendin-4[j]. journal of pharmacology and experimental therapeutics, 2002, 302(3): 881-888.sharma a, srenby a, wernerson a, et al. exendin-4 treatment improves metabolic control after rat islet transplantation to athymic mice with streptozotocin-induced diabetes[j]. diabetologia, 2006, 49(6): 1247-1253.
Check Digit Verification of cas no
The CAS Registry Mumber 141758-74-9 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,4,1,7,5 and 8 respectively; the second part has 2 digits, 7 and 4 respectively.
Calculate Digit Verification of CAS Registry Number 141758-74:
(8*1)+(7*4)+(6*1)+(5*7)+(4*5)+(3*8)+(2*7)+(1*4)=139
139 % 10 = 9
So 141758-74-9 is a valid CAS Registry Number.
InChI:InChI=1S/C184H282N50O60S/c1-16-94(10)147(178(289)213-114(52-58-144(257)258)163(274)218-121(73-101-77-195-105-39-24-23-38-103(101)105)168(279)215-116(68-90(2)3)165(276)205-107(41-26-28-61-186)158(269)219-122(75-134(189)243)154(265)198-79-135(244)196-83-139(248)231-63-30-43-129(231)175(286)225-127(87-238)174(285)223-125(85-236)155(266)200-80-136(245)202-96(12)181(292)233-65-32-45-131(233)183(294)234-66-33-46-132(234)182(293)232-64-31-44-130(232)176(287)222-124(84-235)150(190)261)229-170(281)119(71-99-34-19-17-20-35-99)217-166(277)117(69-91(4)5)214-159(270)108(42-29-62-194-184(191)192)212-177(288)146(93(8)9)228-151(262)95(11)203-156(267)111(49-55-141(251)252)208-161(272)112(50-56-142(253)254)209-162(273)113(51-57-143(255)256)210-164(275)115(59-67-295-15)211-160(271)110(47-53-133(188)242)207-157(268)106(40-25-27-60-185)206-172(283)126(86-237)224-167(278)118(70-92(6)7)216-169(280)123(76-145(259)260)220-173(284)128(88-239)226-180(291)149(98(14)241)230-171(282)120(72-100-36-21-18-22-37-100)221-179(290)148(97(13)240)
