| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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Purity: ≥98%
GRA Ex-25 is a novel and potent inhibitor of glucagon receptor with IC50 of 56 and 55 nM for rat and human glucagon receptors, respectively. In our assay conditions, GRA Ex-25 binds a human glucagon receptor (h-GlucRbind) with a Ki of 63 nM and a moderate glucagon-induced adenylate cyclase inhibition (h-GlucRcyclase) with a Ki of 254 nM. GRA Ex-25 exhibits a comparable affinity (IC50=56 and 55 nM, respectively) for the rat and human glucagon receptors. When glucagon is administered exogenously to rats, GRA Ex-25 (3 mg/kg, i.v.) dramatically lowers blood glucose levels. Thanks primarily to its direct inhibition of glucagon-stimulated hepatic glucose output, GRA Ex-25 can block the rise in blood glucose levels caused by exogenous administered glucagon.
| Targets |
rat glucagon receptor ( IC50 = 56 nM ); human glucagon receptor ( IC50 = 55 nM )
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|---|---|
| ln Vitro |
GRA Ex-25 exhibits a 63 nM Ki for the human glucagon receptor (h-GlucRbind) and a 254 nM Ki for the moderate glucagon-induced adenylate cyclase inhibition (h-GlucRcyclase) in our assay[1]. The affinity of GRA Ex-25 for the rat and human glucagon receptors is comparable (IC50=56 and 55 nM, respectively)[2].
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| ln Vivo |
GRA Ex-25 (3 mg/kg, i.v.) dramatically lowers blood glucose brought on by exogenous glucagon administration in rat model. Because GRA Ex-25 directly inhibits glucagon-stimulated hepatic glucose output, it can prevent the rise in blood glucose levels brought on by exogenous glucagon administration[2].
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| Animal Protocol |
Male Sprague Dawley rats weighing 200 grams who have not fasted are kept anesthetized throughout the test by intraperitoneal injection of a 1:1 combination of Hypnorm (fentanyl, 0.05 mg/mL and fluanizone, 2.5 mg/mL) and Dormicum (midazolam, 1.25 mg/mL). In order to administer compounds, an catheter is placed in the jugular vein. Test compounds (0, 1, 3, 10, and 30 mg/kg) and glucagon (3 μg/kg) are given in intervals of 5 minutes, approximately 60 minutes after the anesthesia is started. Samples for determination of blood glucose concentrations are taken from the tail tip 25 and 5 min prior to administration of the compound to represent average basal values and again 10 min after administration of glucagon (time for peak response of glucagon). The values obtained 10 minutes after alucagon administration are subtracted from the average of the two basal values to express the results as delta values.
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| References |
| Molecular Formula |
C29H36F3N3O5
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|---|---|
| Molecular Weight |
563.60844
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| Exact Mass |
563.261
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| Elemental Analysis |
C, 61.80; H, 6.44; F, 10.11; N, 7.46; O, 14.19
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| CAS # |
307983-31-9
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| PubChem CID |
16100296
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| Appearance |
Solid powder
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| LogP |
6.892
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
40
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| Complexity |
839
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(O)CCNC(C1=CC=C(CN([C@H]2CC[C@H](C(C)(C)C)CC2)C(NC3=CC=C(OC(F)(F)F)C=C3)=O)C=C1)=O
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| InChi Key |
BZXMLCVDKDXRQY-LOSWNTGBSA-N
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| InChi Code |
InChI=1S/C29H36F3N3O5/c1-28(2,3)21-8-12-23(13-9-21)35(27(39)34-22-10-14-24(15-11-22)40-29(30,31)32)18-19-4-6-20(7-5-19)26(38)33-17-16-25(36)37/h4-7,10-11,14-15,21,23H,8-9,12-13,16-18H2,1-3H3,(H,33,38)(H,34,39)(H,36,37)/t21?,23-
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| Chemical Name |
3-(4-((1-(4-(tert-butyl)cyclohexyl)-3-(4-(trifluoromethoxy)phenyl)ureido)methyl)benzamido)propanoic acid
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| Synonyms |
GRA Ex25; GRA Ex-25; GRAEx 25; GRA Ex 25; GRAEx-25; GRAEx25
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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 |
| 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: ≥ 32 mg/mL (~56.8 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.44 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (3.69 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (3.69 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7743 mL | 8.8714 mL | 17.7428 mL | |
| 5 mM | 0.3549 mL | 1.7743 mL | 3.5486 mL | |
| 10 mM | 0.1774 mL | 0.8871 mL | 1.7743 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.
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