| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg | |||
| Other Sizes |
| Targets |
GLP-2 receptor (GLP-2R). GLP-2(3-33) is a naturally occurring antagonist of the GLP-2 receptor, which is a class B GPCR primarily expressed in the gastrointestinal tract, as well as in the brain. It competitively blocks the action of the endogenous agonist, GLP-2.
|
|---|---|
| ln Vitro |
GLP-2 is secreted as a 33-amino acid peptide, but dipeptidylpeptidase IV (DPPIV) quickly breaks it down at an N-terminus site to GLP-2(3-33) in circulation. On the GLP-2 receptor, GLP-2 (3-33), functions as a partial agonist with possible competitive antagonistic qualities. The binding IC50 for GLP-21-33 in the GLP-2 receptor-binding assay was 41 nM, and it was 3.1 nM for GLP-2 1-33. Therefore, compared to GLP-2 1-33, GLP-2 3–33 had a 7.5% binding affinity[1].
GLP-2(3-33) is a potent and selective antagonist of the GLP-2 receptor. It is produced in vivo by the enzymatic cleavage of GLP-2 by DPP-4, making it a negative regulator of the GLP-2 system. The Kd for binding to the human GLP-2 receptor is approximately 8.4 nM, and the IC50 for blocking GLP-2-stimulated cAMP production is 10.3 nM. |
| ln Vivo |
In HFD-fed mice, GLP-2(3–33) (60 ng; once daily intraperitoneally for four weeks) causes dyslipidemia and hepatic lipid accumulation[2].
|
| Enzyme Assay |
A cell-free radioligand binding assay is performed using membranes from BHK (baby hamster kidney) cells transfected with the human GLP-2 receptor. The membranes are incubated with [125I]-GLP-2 and varying concentrations of unlabeled GLP-2(3-33). After incubation, bound and free ligands are separated by filtration to calculate the Kd.
|
| Cell Assay |
For a functional cellular assay, BHK cells stably expressing the human GLP-2 receptor are seeded in 96-well plates. Cells are pre-incubated with varying concentrations of GLP-2(3-33) and then stimulated with a fixed, submaximal concentration of GLP-2. After lysis, intracellular cAMP levels are measured using a HTRF or chemiluminescence-based immunoassay to determine the antagonist's IC50.
|
| Animal Protocol |
Animal/Disease Models: Male C57BL/6J (B6) mice (HFD)[2]
Doses: 60 ng Route of Administration: one time/day ip for 4 weeks Experimental Results: Dramatically affected plasma lipids; demonstrated increase of triglycerides and cholesterol and reduction of HDL; Dramatically increased plasma ALT and AST and intrahepatic lipid concentration. To study the effects of blocking endogenous GLP-2 signaling, GLP-2(3-33) can be administered in vivo. In rodent models, it is administered via intraperitoneal (i.p.) injection. For example, in studies of intestinal injury, the antagonist can be co-administered with GLP-2 to see if it blocks the beneficial trophic (growth-promoting) effects of GLP-2 on the intestinal mucosa. |
| ADME/Pharmacokinetics |
Not reported. As a naturally occurring peptide, it is produced in vivo by the action of the ubiquitous enzyme DPP-4. Exogenous GLP-2(3-33) is rapidly degraded in the circulation, limiting its utility as a therapeutic but making it a useful tool for acute studies.
|
| Toxicity/Toxicokinetics |
Not reported. As an endogenous peptide, GLP-2(3-33) is likely to be safe. Blocking the GLP-2R could lead to reduced intestinal growth and function. In some pathological contexts, such as cancer, GLP-2 is a growth factor, and its antagonist could theoretically have anti-proliferative effects.
|
| References |
[1]. Thulesen J, Knudsen LB, Hartmann B, Hastrup S, Kissow H, Jeppesen PB, Ørskov C, Holst JJ, Poulsen SS. The truncated metabolite GLP-2 (3-33) interacts with the GLP-2 receptor as a partial agonist. Regul Pept. 2002 Jan 15;103(1):9-15.
[2]. Baldassano S, et al. Influence of endogenous glucagon-like peptide-2 on lipid disorders in mice fed a high-fat diet. Endocr Res. 2016 Nov;41(4):317-324. |
| Additional Infomation |
GLP-2(3-33) is a key component of the natural regulatory biology of the GLP-2 system. The full-length GLP-2 peptide is a potent intestinotrophic hormone, promoting intestinal growth and repair, making it a valuable therapeutic for short bowel syndrome (e.g., teduglutide). The existence of its endogenous antagonist GLP-2(3-33) reveals a feedback mechanism that tightly controls GLP-2-mediated growth signals, preventing overgrowth. This compound is an essential tool for understanding this delicate balance.
|
| Molecular Formula |
C156H242N40O53S
|
|---|---|
| Molecular Weight |
3557.89191675186
|
| Exact Mass |
3556.722
|
| CAS # |
275801-62-2
|
| Related CAS # |
GLP-2(3-33) (Leu-13C6,15N);GLP-2(3-33) (Leu-13C6,15NN) (TFA)
|
| PubChem CID |
71455345
|
| Appearance |
Typically exists as solid at room temperature
|
| LogP |
-14.1
|
| Hydrogen Bond Donor Count |
52
|
| Hydrogen Bond Acceptor Count |
57
|
| Rotatable Bond Count |
120
|
| Heavy Atom Count |
250
|
| Complexity |
8480
|
| Defined Atom Stereocenter Count |
37
|
| SMILES |
CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CC3=CC=CC=C3)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC4=CC=CC=C4)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CC(=O)O)N
|
| InChi Key |
MYKFSDGCGNRIEA-KXTJMAPWSA-N
|
| InChi Code |
InChI=1S/C156H242N40O53S/c1-21-73(11)119(148(241)175-90(44-46-108(159)202)133(226)194-123(79(17)199)152(245)174-88(42-33-34-49-157)132(225)190-122(76(14)24-4)151(244)196-124(80(18)200)153(246)188-105(155(248)249)65-118(217)218)191-143(236)95(54-72(9)10)177-137(230)98(57-84-66-166-87-41-32-31-40-85(84)87)180-139(232)100(60-110(161)204)187-149(242)120(74(12)22-2)192-144(237)97(56-83-38-29-26-30-39-83)178-141(234)103(63-116(213)214)183-129(222)89(43-35-50-165-156(163)164)171-127(220)78(16)168-126(219)77(15)169-134(227)93(52-70(5)6)176-138(231)99(59-109(160)203)182-142(235)104(64-117(215)216)184-135(228)94(53-71(7)8)186-150(243)121(75(13)23-3)193-154(247)125(81(19)201)195-145(238)101(61-111(162)205)181-131(224)92(48-51-250-20)173-130(223)91(45-47-113(207)208)172-140(233)102(62-115(211)212)185-147(240)107(69-198)189-136(229)96(55-82-36-27-25-28-37-82)179-146(239)106(68-197)170-112(206)67-167-128(221)86(158)58-114(209)210/h25-32,36-41,66,70-81,86,88-107,119-125,166,197-201H,21-24,33-35,42-65,67-69,157-158H2,1-20H3,(H2,159,202)(H2,160,203)(H2,161,204)(H2,162,205)(H,167,221)(H,168,219)(H,169,227)(H,170,206)(H,171,220)(H,172,233)(H,173,223)(H,174,245)(H,175,241)(H,176,231)(H,177,230)(H,178,234)(H,179,239)(H,180,232)(H,181,224)(H,182,235)(H,183,222)(H,184,228)(H,185,240)(H,186,243)(H,187,242)(H,188,246)(H,189,229)(H,190,225)(H,191,236)(H,192,237)(H,193,247)(H,194,226)(H,195,238)(H,196,244)(H,207,208)(H,209,210)(H,211,212)(H,213,214)(H,215,216)(H,217,218)(H,248,249)(H4,163,164,165)/t73-,74-,75-,76-,77-,78-,79+,80+,81+,86-,88-,89-,90-,91-,92-,93-,94-,95-,96-,97-,98-,99-,100-,101-,102-,103-,104-,105-,106-,107-,119-,120-,121-,122-,123-,124-,125-/m0/s1
|
| Chemical Name |
(2S)-2-[[(2S,3R)-2-[[(2S,3S)-2-[[(2S)-6-amino-2-[[(2S,3R)-2-[[(2S)-5-amino-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,3S)-2-[[(2S,3R)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-amino-3-carboxypropanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]-3-phenylpropanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]-4-carboxybutanoyl]amino]-4-methylsulfanylbutanoyl]amino]-4-oxobutanoyl]amino]-3-hydroxybutanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoyl]amino]-3-carboxypropanoyl]amino]-4-oxobutanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]propanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-carboxypropanoyl]amino]-3-phenylpropanoyl]amino]-3-methylpentanoyl]amino]-4-oxobutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-4-methylpentanoyl]amino]-3-methylpentanoyl]amino]-5-oxopentanoyl]amino]-3-hydroxybutanoyl]amino]hexanoyl]amino]-3-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]butanedioic acid
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.2811 mL | 1.4053 mL | 2.8107 mL | |
| 5 mM | 0.0562 mL | 0.2811 mL | 0.5621 mL | |
| 10 mM | 0.0281 mL | 0.1405 mL | 0.2811 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
