| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
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| Targets |
OX2 (EC50 = 0.13 nM); OX1 (EC50 = 52 nM)
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|---|---|
| ln Vitro |
Investigation of l-alanine and d-amino acid replacement of orexin-B revealed that three l-leucine residues at the positions of 11, 14, and 15 in orexin-B were important to show selectivity for the orexin-2 receptor (OX2) over the orexin-1 receptor (OX1). l-Alanine substitution at position 11 and d-leucine substitution at positions 14 and 15 maintained the potency of orexin-B to mobilize [Ca2+]i in CHO cells expressing the OX2, while their potency for the OX1 was significantly reduced. In combined substitutions, we identified that [Ala11, D-Leu15] Orexin-B showed a 400-fold selectivity for the OX2 (EC50=0.13 nM) over OX1 (EC50=52 nM). [Ala11, d-Leu15]orexin-B is a beneficial tool for addressing the functional roles of the OX2 [1].
|
| ln Vivo |
OX2R Agonist Prevents Diet-Induced Obesity[2]
Our genetic studies implicate the OX2R pathway as mediator of the effects of orexin overexpression upon energy homeostasis. To further test the hypothesis that central enhancement of orexin-OX2R signaling confers resistance to diet-induced obesity, an OX2R selective agonist [Ala11, D-Leu15] Orexin-B (Asahi et al., 2003) was continuously infused in the lateral ventricles of wild-type mice for 14 days. The administration of the OX2R selective agonist suppressed weight gain on a high-fat diet without altering weight homeostasis on a low-fat diet (Figure 5A). Importantly, the OX2R selective agonist had no obvious effect upon OX2R-deficient mice on a high-fat diet (n = 4, weight gain 3.33 ± 0.61 g, p = 0.67), verifying the specificity of the agonist in vivo. Following 14 days, the agonist-infused wild-type mice gained significantly less fat mass than did the vehicle-injected mice on a high-fat diet, and no effect was observed on a low-fat diet (Figure 5B). When centrally infused mice fed a high-fat diet were monitored in metabolic chambers, OX2R agonist infusions resulted in consistently greater energy expenditures (Figure 5C), but not RQs (Figure 5D) or locomotor activity (data not shown), over vehicle-infused controls. |
| Animal Protocol |
To further test the hypothesis that central enhancement of orexin-OX2R signaling confers resistance to diet-induced obesity, an OX2R selective agonist [Ala11, D-Leu15] Orexin-B (Asahi et al., 2003) was continuously infused in the lateral ventricles of wild-type mice for 14 days. The administration of the OX2R selective agonist suppressed weight gain on a high-fat diet without altering weight homeostasis on a low-fat diet (Figure 5A).[2]
Chronic ICV Injection [2] Three- to four-month-old male C57B/6J mice were single-housed 1 week before surgery and fed a low-fat diet. Mice were anesthetized with ketamine and xylazine (100 mg/Kg and 10 mg/Kg, respectively, i.p.). A cannula was implanted into the right lateral ventricle (0.3 mm posterior from the bregma, 0.9 mm lateral from the midline, and 2.4 mm from the surface of skull) using standard sterile stereotactic techniques. An osmotic minipump (model 2001; Alzet) was attached to the cannula and implanted in the subcutaneous space during the same surgical session. The OX2R selective agonist ([Ala11, D-Leu15] Orexin-B) (Asahi et al., 2003) or vehicle was continuously injected in the lateral ventricle for 14 days (0.5 nmol/day). The agonist was diluted with vehicle immediately before use. At the day of surgery, the implanted mice were randomly assigned to a low-fat diet or a high-fat diet. Body weight and food intake were monitored daily for 14 days, and fat mass was detected by NMR immediately after surgery and again at day 14. Twelve-week-old ob/ob male mice were used for chronic ICV infusion of OX2R agonist for 10 days as described above. For leptin administration experiments, weight-matched 3- to 4-month-old CAG/orexin and wild-type littermates were continuously injected with leptin (2 μg/day), as described above, while maintained on a low-fat diet. Body weight and food intake were monitored daily for 14 days. |
| References | |
| Additional Infomation |
In conclusion, [Ala11, d-Leu15]orexin-B identified in the course of the l-alanine and d-amino acid replacements of orexin-B is a potent and selective OX2 agonist. A novel agonist, [Ala11, d-Leu15]orexin-B should be a promising tool for addressing the roles of OX2. [1]
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| Molecular Formula |
C120H206N44O35S
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|---|---|
| Molecular Weight |
2857.25843999999
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| Exact Mass |
2855.541
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| CAS # |
532932-99-3
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| Related CAS # |
[Ala11,D-Leu15]-Orexin B(human) TFA
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| PubChem CID |
90473850
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| Sequence |
Arg-Ser-Gly-Pro-Pro-Gly-Leu-Gln-Gly-Arg-Ala-Gln-Arg-Leu-Leu-Gln-Ala-Ser-Gly-Asn-His-Ala-Ala-Gly-Ile-Leu-Thr-Met-NH2; H-Arg-Ser-Gly-Pro-Pro-Gly-Leu-Gln-Gly-Arg-Ala-Gln-Arg-Leu-D-Leu-Gln-Ala-Ser-Gly-Asn-His-Ala-Ala-Gly-Ile-Leu-Thr-Met-NH2; L-arginyl-L-seryl-glycyl-L-prolyl-L-prolyl-glycyl-L-leucyl-L-glutaminyl-glycyl-L-arginyl-L-alanyl-L-glutaminyl-L-arginyl-L-leucyl-D-leucyl-L-glutaminyl-L-alanyl-L-seryl-glycyl-L-asparagyl-L-histidyl-L-alanyl-L-alanyl-glycyl-L-isoleucyl-L-leucyl-L-threonyl-L-methioninamide
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| SequenceShortening |
RSGPPGLQGRAQRLLQASGNHAAGILTM; RSGPPGLQGRAQRLLQASGNHAAGILTM-NH2
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| Appearance |
White to off-white solid powder
|
| Density |
1.5±0.1 g/cm3
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| Index of Refraction |
1.670
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| LogP |
-10.7
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| Hydrogen Bond Donor Count |
44
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| Hydrogen Bond Acceptor Count |
41
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| Rotatable Bond Count |
97
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| Heavy Atom Count |
200
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| Complexity |
6570
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| Defined Atom Stereocenter Count |
25
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| SMILES |
CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCSC)C(=O)N)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](CC(=O)N)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@@H]2CCCN2C(=O)[C@@H]3CCCN3C(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(=N)N)N
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| InChi Key |
SURUUKNICBOUOQ-UBNRXWOCSA-N
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| InChi Code |
InChI=1S/C120H206N44O35S/c1-17-60(10)93(115(197)158-77(44-59(8)9)113(195)162-94(65(15)167)116(198)150-68(95(126)177)34-40-200-16)161-91(175)51-137-96(178)61(11)143-97(179)62(12)146-108(190)78(45-66-47-133-55-142-66)157-112(194)79(46-87(125)171)149-89(173)49-139-102(184)80(53-165)159-99(181)64(14)145-105(187)72(29-32-85(123)169)154-110(192)75(42-57(4)5)156-111(193)76(43-58(6)7)155-106(188)70(25-20-37-136-120(131)132)152-107(189)73(30-33-86(124)170)151-98(180)63(13)144-104(186)69(24-19-36-135-119(129)130)147-88(172)48-138-101(183)71(28-31-84(122)168)153-109(191)74(41-56(2)3)148-90(174)50-140-114(196)82-26-21-39-164(82)117(199)83-27-22-38-163(83)92(176)52-141-103(185)81(54-166)160-100(182)67(121)23-18-35-134-118(127)128/h47,55-65,67-83,93-94,165-167H,17-46,48-54,121H2,1-16H3,(H2,122,168)(H2,123,169)(H2,124,170)(H2,125,171)(H2,126,177)(H,133,142)(H,137,178)(H,138,183)(H,139,184)(H,140,196)(H,141,185)(H,143,179)(H,144,186)(H,145,187)(H,146,190)(H,147,172)(H,148,174)(H,149,173)(H,150,198)(H,151,180)(H,152,189)(H,153,191)(H,154,192)(H,155,188)(H,156,193)(H,157,194)(H,158,197)(H,159,181)(H,160,182)(H,161,175)(H,162,195)(H4,127,128,134)(H4,129,130,135)(H4,131,132,136)/t60-,61-,62-,63-,64-,65+,67-,68-,69-,70-,71-,72-,73-,74-,75+,76-,77-,78-,79-,80-,81-,82-,83-,93-,94-/m0/s1
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| Chemical Name |
(2S)-N-[(2S)-1-[[(2S)-1-[[(2R)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-4-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S,3S)-1-[[(2S)-1-[[(2S,3R)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-2-oxoethyl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-5-amino-2-[[(2S)-2-[[2-[[(2S)-1-[(2S)-1-[2-[[(2S)-2-[[(2S)-2-amino-5-carbamimidamidopentanoyl]amino]-3-hydroxypropanoyl]amino]acetyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carbonyl]amino]acetyl]amino]-4-methylpentanoyl]amino]-5-oxopentanoyl]amino]acetyl]amino]-5-carbamimidamidopentanoyl]amino]propanoyl]amino]pentanediamide
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| Synonyms |
[Ala11,D-Leu15]-Orexin B; 532932-99-3; (Ala11,d-leu15)-orexin b(human); [Ala11,D-Leu15]-Orexin B TFA;
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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) |
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 | 0.3500 mL | 1.7499 mL | 3.4999 mL | |
| 5 mM | 0.0700 mL | 0.3500 mL | 0.7000 mL | |
| 10 mM | 0.0350 mL | 0.1750 mL | 0.3500 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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