Beinaglutide is a novel recombinant human GLP-1 (rhGLP-1) with high homology (~100%) with human GLP-1 (7–36). It has the potential for the treatment of overweight/obesity and nonalcoholic steatohepatitis (NASH). Beinaglutide exhibits does-dependent effects in glycemic control, acting by inhibiting food intake and gastric empty and promoting weight loss.
Physicochemical Properties
| Molecular Formula | C149H225N39O46 |
| Molecular Weight | 3298.61453509331 |
| Exact Mass | 3297.649 |
| CAS # | 123475-27-4 |
| PubChem CID | 131801470 |
| Appearance | White to off-white solid powder |
| LogP | -13.6 |
| Hydrogen Bond Donor Count | 49 |
| Hydrogen Bond Acceptor Count | 51 |
| Rotatable Bond Count | 109 |
| Heavy Atom Count | 234 |
| Complexity | 7660 |
| Defined Atom Stereocenter Count | 30 |
| SMILES | CC[C@H](C)[C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)O)NC(=O)[C@H](CC3=CC=CC=C3)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(=O)N)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC4=CC=C(C=C4)O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(=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]([C@@H](C)O)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](CC6=CNC=N6)N |
| InChi Key | NGJOFQZEYQGZMB-KTKZVXAJSA-N |
| InChi Code | InChI=1S/C149H225N39O46/c1-17-76(10)119(145(230)166-80(14)125(210)174-104(60-86-63-158-91-36-25-24-35-89(86)91)135(220)176-100(56-73(4)5)136(221)185-117(74(6)7)143(228)173-92(37-26-28-52-150)127(212)159-66-111(197)168-98(148(233)234)39-30-54-157-149(154)155)187-137(222)102(57-83-31-20-18-21-32-83)177-132(217)97(47-51-115(203)204)172-131(216)93(38-27-29-53-151)169-123(208)78(12)163-122(207)77(11)165-130(215)96(44-48-109(153)195)167-110(196)65-160-129(214)95(46-50-114(201)202)171-133(218)99(55-72(2)3)175-134(219)101(59-85-40-42-88(194)43-41-85)178-140(225)106(68-189)181-142(227)108(70-191)182-144(229)118(75(8)9)186-139(224)105(62-116(205)206)179-141(226)107(69-190)183-147(232)121(82(16)193)188-138(223)103(58-84-33-22-19-23-34-84)180-146(231)120(81(15)192)184-112(198)67-161-128(213)94(45-49-113(199)200)170-124(209)79(13)164-126(211)90(152)61-87-64-156-71-162-87/h18-25,31-36,40-43,63-64,71-82,90,92-108,117-121,158,189-194H,17,26-30,37-39,44-62,65-70,150-152H2,1-16H3,(H2,153,195)(H,156,162)(H,159,212)(H,160,214)(H,161,213)(H,163,207)(H,164,211)(H,165,215)(H,166,230)(H,167,196)(H,168,197)(H,169,208)(H,170,209)(H,171,218)(H,172,216)(H,173,228)(H,174,210)(H,175,219)(H,176,220)(H,177,217)(H,178,225)(H,179,226)(H,180,231)(H,181,227)(H,182,229)(H,183,232)(H,184,198)(H,185,221)(H,186,224)(H,187,222)(H,188,223)(H,199,200)(H,201,202)(H,203,204)(H,205,206)(H,233,234)(H4,154,155,157)/t76-,77-,78-,79-,80-,81+,82+,90-,92-,93-,94-,95-,96-,97-,98-,99-,100-,101-,102-,103-,104-,105-,106-,107-,108-,117-,118-,119-,120-,121-/m0/s1 |
| Chemical Name | (4S)-5-[[2-[[(2S,3R)-1-[[(2S)-1-[[(2S,3R)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[2-[[(1S)-4-carbamimidamido-1-carboxybutyl]amino]-2-oxoethyl]amino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-2-oxoethyl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-2-oxoethyl]amino]-4-[[(2S)-2-[[(2S)-2-amino-3-(1H-imidazol-4-yl)propanoyl]amino]propanoyl]amino]-5-oxopentanoic 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 (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) |
Biological Activity
| ln Vitro | In adipocytes induced by increased insulin, benaglutide (100 nM; 48 hours) increases the expression of Akt phosphorylation [2]. |
| ln Vivo | In mice, beenaglutide (0.6, 1.2, 2.4 mg/kg; sc; three times daily for seven days) has been demonstrated to lower body weight, suppress food intake, and regulate blood sugar [1]. Adipocytes are more sensitive to insulin when benaglutide (150 μg/kg; sc; once daily for 6 weeks) is administered [2]. |
| Cell Assay |
Western Blot Analysis[2] Cell Types: 3T3L-1 cells Tested Concentrations: 100 nM Incubation Duration: 48 h Experimental Results: Increased the phosphorylation of Akt in the adipocytes that were potentiated insulin-stimulated. |
| Animal Protocol |
Animal/Disease Models: Wild-type male C57BL/6 mice and Male Lepob/Lepob (ob/ob) mice (ob/ob-NASH mouse model was induced by GAN diet)[1] Doses: 0.6, 1.2, 2.4 mg/kg Route of Administration: Sc; three times per day for 7 days Experimental Results: Dramatically decreased blood glucose with dosedependence in C57BL/6 and ob/ob mice, dose dependently inhibits food intake and gastric Emptying, and Dramatically decreased body weight, food intake with dose-dependence . Animal/Disease Models: Eightweeks old male C57BL/6 mice[2] Doses: 150 µg/kg Route of Administration: Sc; daily for 6 weeks Experimental Results: demonstrated improved glucose tolerance and insulin sensitivity, diminished adipose tissue weight and adipocyte size and potentiated insulin sensitivity of adipocytes. |
| References |
[1]. Fang X, et al. Beinaglutide shows significantly beneficial effects in diabetes/obesity-induced nonalcoholic steatohepatitis in ob/ob mouse model. Life Sci. 2021 Apr 1;270:118966. [2]. Zhang F, et al. Recombinant human GLP-1 beinaglutide regulates lipid metabolism of adipose tissues in diet-induced obese mice. iScience. 2021 Oct 30;24(12):103382. |
| Additional Infomation | Beinaglutide is under investigation in clinical trial NCT03829891 (Study for Beinaglutide Versus Glargine Therapy in Glycemic Variability of Type 2 Diabetes Mellitus). |
Solubility Data
| Solubility (In Vitro) | DMSO : ~1.79 mg/mL (~0.54 mM) |
| 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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.3032 mL | 1.5158 mL | 3.0316 mL | |
| 5 mM | 0.0606 mL | 0.3032 mL | 0.6063 mL | |
| 10 mM | 0.0303 mL | 0.1516 mL | 0.3032 mL |