| ln Vivo |
Davalintide (1.09-1087 μg/kg (mice); 5 μg/kg (volume), intraperitoneal injection, single dose) can inhibit the food effects of food sources and overfeeding, and its toxicity and duration are similar to those of Amylin[1]. Davalintide (1-100 μg/kg, intraperitoneal injection, single dose) Davalintide (1-100 μg/kg, subcutaneous injection, once daily, continuous infusion for 8 weeks) can effectively reduce food intake and weight. Its weight loss is mainly reflected in fat reduction, while maintaining lean body mass. Its supplementation is far more than just restricting food intake[1]. Davalintide (10 μg/kg, subcutaneous injection, once daily, continuous infusion for 4 weeks) significantly reduces total stored calories, reduces preference for high-fat and delicious foods, and promotes selection of standard feed[1]. Davalintide (10 μg/kg, intraperitoneal injection, single dose) has a significant effect on the posterior brainstem area, achieving the effect of inhibiting the response by activating the downstream neural response of the stimulus more persistently[1]. Davalintide (10 μg/kg, subcutaneous injection, single dose) has a significant inhibitory effect on the posterior brainstem and also has a significant inhibitory effect on the inhibitory effect of glucagon [2].
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|---|---|
| Animal Protocol |
Animal/Disease Models: Acute food intake inhibition experiment established in fasted overnight NIH Swiss mice (24-30 g) and overfed Sprague-Dawley (SD) rats (weighing 394-461 g)[1]
Doses: 1.09-1087 μg/kg (mice); 5 μg/kg (rats) Route of Administration: Intraperitoneal injection (i.p.), single dose Experimental Results: And Amylin both significantly and dose-dependently inhibited acute food intake (mice ED50: 87 μg/kg vs. Amylin 110 μg/kg) Exhibited the duration of action significantly longer than that of Amylin (23 hours vs. 6 hours) in the experiment where obese rats were subjected to the dark cycle (the main feeding period). Animal/Disease Models: Behavioral safety experiment established fasted Sprague-Dawley (SD) rats (weighing 325-425 g)[1] Doses: 1, 10, 100 μg/kg Route of Administration: Intraperitoneal injection (i.p.), single dose Experimental Results: Dose-dependently and persistently reduced food intake and body weight (8-week ED50 = 1.2 μg/kg/day). Significantly reduced the level of plasma triglycerides. Animal/Disease Models: Continuous infusion experiment (metabolic effect) established in obese rats induced by diet (Levin or SD rats, ~464 g), maintained on a 32% high-fat diet[1] Doses: 1, 3, 10, 100 μg/kg Route of Administration: Subcutaneous injection (s.c.), once daily for 8 weeks Experimental Results: Dose-dependently and persistently reduced food intake and body weight (8-week ED50 = 1.2 μg/kg/day). Significantly reduced the level of plasma triglycerides. Animal/Disease Models: Food preference experiment established in DIO rats (~ 515 g) provided with both standard feed and 32% high-fat feed for them to choose freely[1] Doses: 10 μg/kg Route of Administration: Subcutaneous injection (s.c.), once daily for 4 weeks Experimental Results: Significantly reduced total calorie intake. Significantly reduced the preference for high-fat and delicious foods, and prompted the animals to choose standard feed. Animal/Disease Models: Energy metabolism experiment established in SD rats (~ 421 g), maintained on a 32% high-fat diet for 5 weeks[1] Doses: 30 μg/kg Route of Administration: Subcutaneous injection (s.c.), once daily for 4 weeks Experimental Results: Exhibited the energy consumption (VO₂) of not different from that in the Vehicle group. Slight but significant increased RQ values at the end of the second week. Animal/Disease Models: Area postrema (AP) damage experiment established in SD rats (weighing 175-200 g) underwent AP lesion surgery or sham surgery, and the experiments were conducted several months after recovery[1] Doses: 10 μg/kg Route of Administration: Intraperitoneal injection (i.p.), single dose Experimental Results: Significantly reduced food intake in the sham operation group. Completely eliminated the effect of suppressing appetite in the AP lesion group. Animal/Disease Models: Neuronal activation (c-Fos expression) established in SD rats (400 g), maintained on a 32% high-fat diet[1] Doses: 10 μg/kg Route of Administration: Intraperitoneal injection (i.p.), single dose Experimental Results: Activated the same neural pathways to Amylin, but its effects lasted longer. Animal/Disease Models: Glucagon inhibition experiment established in starved SD rats (250-280 g) and SD rats (350-370 g)[2] Doses: 10 μg/kg Route of Administration: Subcutaneous injection (s.c.), single dose Experimental Results: Significantly inhibited the glucagon secretion stimulated by arginine. Was no difference in blood glucose and insulin levels during the clamp period. |
| References |
| Molecular Formula |
C152H248N50O49S2
|
|---|---|
| Molecular Weight |
3624.03
|
| Exact Mass |
3622.793
|
| CAS # |
863919-85-1
|
| PubChem CID |
71587842
|
| Sequence |
Lys-Cys-Asn-Thr-Ala-Thr-Cys-Val-Leu-Gly-Arg-Leu-Ser-Gln-Glu-Leu-His-Arg-Leu-Gln-Thr-Tyr-Pro-Arg-Thr-Asn-Thr-Gly-Ser-Asn-Thr-Tyr-NH2 (disulfide bridge:Cys2-Cys7)KCNTATCVLGRLSQELHRLQTYPRTNTGSNTY-NH2 (disulfide bridge:Cys2-Cys7)
|
| Appearance |
Typically exists as solids at room temperature
|
| Hydrogen Bond Donor Count |
59
|
| SMILES |
C[C@H]1C(=O)N[C@H](C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N1)[C@@H](C)O)CC(=O)N)NC(=O)[C@H](CCCCN)N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC2=CN=CN2)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC3=CC=C(C=C3)O)C(=O)N4CCC[C@H]4C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC5=CC=C(C=C5)O)C(=O)N)[C@@H](C)O
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| InChi Key |
SLYFITHISHUGLZ-QPMCIWSFSA-N
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| InChi Code |
InChI=1S/C152H248N50O49S2/c1-66(2)48-91(189-143(245)113(70(9)10)195-140(242)103-64-253-252-63-102(193-122(224)83(154)24-18-19-43-153)139(241)188-97(56-108(158)216)135(237)200-115(73(13)206)144(246)174-71(11)121(223)196-116(74(14)207)148(250)194-103)123(225)171-59-110(218)175-84(25-20-44-168-150(161)162)124(226)183-94(51-69(7)8)132(234)192-101(62-204)138(240)180-87(37-40-105(155)213)126(228)178-89(39-42-112(220)221)127(229)185-93(50-68(5)6)131(233)186-95(54-80-58-167-65-173-80)133(235)177-85(26-21-45-169-151(163)164)125(227)184-92(49-67(3)4)130(232)179-88(38-41-106(156)214)129(231)199-119(77(17)210)147(249)191-99(53-79-31-35-82(212)36-32-79)149(251)202-47-23-28-104(202)141(243)181-86(27-22-46-170-152(165)166)128(230)198-118(76(16)209)146(248)190-98(57-109(159)217)136(238)197-114(72(12)205)142(244)172-60-111(219)176-100(61-203)137(239)187-96(55-107(157)215)134(236)201-117(75(15)208)145(247)182-90(120(160)222)52-78-29-33-81(211)34-30-78/h29-36,58,65-77,83-104,113-119,203-212H,18-28,37-57,59-64,153-154H2,1-17H3,(H2,155,213)(H2,156,214)(H2,157,215)(H2,158,216)(H2,159,217)(H2,160,222)(H,167,173)(H,171,225)(H,172,244)(H,174,246)(H,175,218)(H,176,219)(H,177,235)(H,178,228)(H,179,232)(H,180,240)(H,181,243)(H,182,247)(H,183,226)(H,184,227)(H,185,229)(H,186,233)(H,187,239)(H,188,241)(H,189,245)(H,190,248)(H,191,249)(H,192,234)(H,193,224)(H,194,250)(H,195,242)(H,196,223)(H,197,238)(H,198,230)(H,199,231)(H,200,237)(H,201,236)(H,220,221)(H4,161,162,168)(H4,163,164,169)(H4,165,166,170)/t71-,72+,73+,74+,75+,76+,77+,83-,84-,85-,86-,87-,88-,89-,90-,91-,92-,93-,94-,95-,96-,97-,98-,99-,100-,101-,102-,103-,104-,113-,114-,115-,116-,117-,118-,119-/m0/s1
|
| Chemical Name |
(4S)-5-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S,3R)-1-[[(2S)-1-[(2S)-2-[[(2S)-1-[[(2S,3R)-1-[[(2S)-4-amino-1-[[(2S,3R)-1-[[2-[[(2S)-1-[[(2S)-4-amino-1-[[(2S,3R)-1-[[(2S)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]carbamoyl]pyrrolidin-1-yl]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(4R,7S,10S,13S,16S,19R)-16-(2-amino-2-oxoethyl)-19-[[(2S)-2,6-diaminohexanoyl]amino]-7,13-bis[(1R)-1-hydroxyethyl]-10-methyl-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]-5-carbamimidamidopentanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-oxopentanoic 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 |
| 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) |
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
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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 | 0.2759 mL | 1.3797 mL | 2.7594 mL | |
| 5 mM | 0.0552 mL | 0.2759 mL | 0.5519 mL | |
| 10 mM | 0.0276 mL | 0.1380 mL | 0.2759 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.