| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg | |||
| Other Sizes |
| Targets |
GLP-1 receptor (GLP-1R) and glucagon receptor (GCGR). Dapiglutide is a balanced dual agonist of both receptors. This balanced activation is hypothesized to produce greater weight loss than selective GLP-1 agonism by both reducing food intake (GLP-1) and increasing energy expenditure (glucagon).
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|---|---|
| ln Vitro |
Dapiglutide is a potent and balanced dual agonist of the GLP-1 and glucagon receptors. The optimal ratio of GLP-1 to glucagon activity is considered key to maximizing weight loss while minimizing the potential hyperglycemic and other side effects associated with pure glucagon agonism. A cell-free binding assay is performed using membranes from cells overexpressing human GLP-1R or GCGR. Membranes are incubated with a radiolabeled ligand ([125I]GLP-1 or [125I]glucagon) and varying concentrations of dapiglutide. After filtration, bound radioactivity is counted to calculate Ki values.
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| Cell Assay |
A functional cellular assay is performed using HEK293 cells stably expressing human GLP-1R or GCGR. Cells are seeded in 96-well plates, treated with varying concentrations of dapiglutide, and intracellular cAMP accumulation is measured using an HTRF or chemiluminescence-based kit to calculate the EC50 for activation of each receptor.
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| Animal Protocol |
In vivo efficacy is typically evaluated in diet-induced obese (DIO) mouse models. Dapiglutide is administered subcutaneously (SC) once weekly for 4-6 weeks. Endpoints include body weight, food intake, glucose tolerance (via OGTT or IPGTT), insulin sensitivity, and histological analysis of liver for fat content and fibrosis to assess NASH.
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| ADME/Pharmacokinetics |
Dapiglutide is a once-weekly peptide, which is achieved through chemical modifications (e.g., acylation with a fatty acid) to bind to serum albumin, thereby prolonging its half-life in circulation. This is a similar strategy to that used for liraglutide and semaglutide. In animals, the half-life is extended to several days, supporting weekly dosing.
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| Toxicity/Toxicokinetics |
In a Phase 1b/2a clinical trial (NCT04707300) in patients with obesity, dapiglutide was generally well-tolerated at the doses tested. The most common side effects were gastrointestinal (nausea, diarrhea), which is typical of GLP-1 receptor agonists. No significant safety signals regarding liver toxicity were reported, supporting its further development.
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| References |
[1]. Zealand Pharma doses first subject in Phase 1 clinical trial with potential next generation dual-acting peptide therapeutic for short bowel syndrome. 26 June 2019.
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| Additional Infomation |
Dapiglutide is being studied in the clinical trial NCT05788601 (dapiroglutide for the treatment of obesity).
Dapiglutide is being developed by Zealand Pharma (now in partnership with Boehringer Ingelheim). This compound is part of a new wave of "unimolecular" dual and triple agonists for metabolic diseases. The concept is that by simultaneously targeting multiple pathways involved in energy balance, greater therapeutic efficacy can be achieved than with single-target drugs. Dapiglutide had positive Phase 2a results for obesity and has been advanced into later-stage trials. |
| Molecular Formula |
C192H302N46O57
|
|---|---|
| Molecular Weight |
4166.79
|
| Exact Mass |
4166.221
|
| CAS # |
2296814-85-0
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| PubChem CID |
171934788
|
| Appearance |
Typically exists as solid at room temperature
|
| Hydrogen Bond Donor Count |
57
|
| Hydrogen Bond Acceptor Count |
62
|
| Rotatable Bond Count |
148
|
| Heavy Atom Count |
295
|
| Complexity |
9920
|
| Defined Atom Stereocenter Count |
40
|
| 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](CC1=CNC=N1)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](CC2=CNC3=CC=CC=C32)NC(=O)[C@H](C)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CC4=CC=CC=C4)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](CCC(=O)N)NC(=O)[C@](C)(CCCCNC(=O)CC[C@@H](C(=O)O)NC(=O)CCCCCCCCCCCCCCCCC(=O)O)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](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC5=CC=CC=C5)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](CC6=CNC=N6)N
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| InChi Key |
ZFSPELIJRGIIEX-HLQWLALHSA-N
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| InChi Code |
InChI=1S/C192H302N46O57/c1-24-101(11)151(181(284)211-108(18)161(264)219-133(84-115-90-203-120-60-49-48-59-118(115)120)172(275)221-130(81-100(9)10)175(278)233-152(102(12)25-2)182(285)218-124(65-70-140(195)244)167(270)224-134(86-117-92-200-97-206-117)173(276)216-121(61-50-52-76-193)169(272)231-154(104(14)27-4)184(287)237-156(111(21)242)185(288)228-137(189(293)294)89-150(259)260)232-176(279)131(82-113-55-42-40-43-56-113)222-174(277)135(87-148(255)256)225-166(269)122(62-54-78-202-191(197)198)214-159(262)106(16)207-158(261)105(15)209-165(268)126(66-71-141(196)245)230-190(295)192(23,75-51-53-77-201-142(246)72-67-127(188(291)292)212-143(247)63-46-38-36-34-32-30-28-29-31-33-35-37-39-47-64-145(249)250)238-180(283)136(88-149(257)258)226-171(274)129(80-99(7)8)227-183(286)153(103(13)26-3)234-187(290)157(112(22)243)235-162(265)109(19)210-170(273)128(79-98(5)6)220-168(271)125(69-74-147(253)254)217-179(282)139(95-240)229-186(289)155(110(20)241)236-177(280)132(83-114-57-44-41-45-58-114)223-178(281)138(94-239)213-144(248)93-204-164(267)123(68-73-146(251)252)215-160(263)107(17)208-163(266)119(194)85-116-91-199-96-205-116/h40-45,48-49,55-60,90-92,96-112,119,121-139,151-157,203,239-243H,24-39,46-47,50-54,61-89,93-95,193-194H2,1-23H3,(H2,195,244)(H2,196,245)(H,199,205)(H,200,206)(H,201,246)(H,204,267)(H,207,261)(H,208,266)(H,209,268)(H,210,273)(H,211,284)(H,212,247)(H,213,248)(H,214,262)(H,215,263)(H,216,276)(H,217,282)(H,218,285)(H,219,264)(H,220,271)(H,221,275)(H,222,277)(H,223,281)(H,224,270)(H,225,269)(H,226,274)(H,227,286)(H,228,288)(H,229,289)(H,230,295)(H,231,272)(H,232,279)(H,233,278)(H,234,290)(H,235,265)(H,236,280)(H,237,287)(H,238,283)(H,249,250)(H,251,252)(H,253,254)(H,255,256)(H,257,258)(H,259,260)(H,291,292)(H,293,294)(H4,197,198,202)/t101-,102-,103-,104-,105-,106-,107-,108-,109-,110+,111+,112+,119-,121-,122-,123-,124-,125-,126-,127-,128-,129-,130-,131-,132-,133-,134-,135-,136-,137-,138-,139-,151-,152-,153-,154-,155-,156-,157-,192-/m0/s1
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| Chemical Name |
(2S)-2-[[(2S,3R)-2-[[(2S,3S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-(1H-imidazol-4-yl)propanoyl]amino]propanoyl]amino]-4-carboxybutanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-4-carboxybutanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-3-hydroxybutanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoyl]amino]-3-carboxypropanoyl]amino]-6-[[(4S)-4-carboxy-4-(17-carboxyheptadecanoylamino)butanoyl]amino]-2-methylhexanoyl]amino]-5-oxopentanoyl]amino]propanoyl]amino]propanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-carboxypropanoyl]amino]-3-phenylpropanoyl]amino]-3-methylpentanoyl]amino]propanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-4-methylpentanoyl]amino]-3-methylpentanoyl]amino]-5-oxopentanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]hexanoyl]amino]-3-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]butanedioic acid
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| HS Tariff Code |
2934.99.9001
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| 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 (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 50 mg/mL (12.00 mM)
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|---|---|
| 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 | 0.2400 mL | 1.2000 mL | 2.3999 mL | |
| 5 mM | 0.0480 mL | 0.2400 mL | 0.4800 mL | |
| 10 mM | 0.0240 mL | 0.1200 mL | 0.2400 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.
Link: https://clinicaltrials.gov/ct2/show/NCT06758583
Conditions:Overweight and ObesityLink: https://clinicaltrials.gov/ct2/show/NCT06000891
Conditions:Safety and TolerabilityLink: https://clinicaltrials.gov/ct2/show/NCT05788601
Conditions:Obesity|Inflammation
Title:A Multiple Ascending Dose Trial Assessing Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ZP7570
Status:Completed
updateDate:2021-09-02
Ctid:NCT04612517
Link: https://clinicaltrials.gov/ct2/show/NCT04612517
Conditions:HealthyProducts are for research use only; We do not sell to patients
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