![[Sar9,Met(O2)11]-Substance P](/upload/1124/V33875.png)
| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 100mg | |||
| Other Sizes |
| Targets |
Tachykinin NK₁ receptor. [1]
|
|---|---|
| ln Vitro |
[Sar9,Met(O2)11]-Heptapeptide (10-100 pmol per rat, icv) and substance P are equal in raising heart rate (HR) and mean arterial blood pressure (MAP), although the processes take different amounts of time. The sole drug that has grooming effects is [Sar9,Met(O2)11]-substance P, although both agonists improve face cleaning and olfaction in a dose-dependent manner [1].
|
| ln Vivo |
[Sar9,Met(O2)11]-Substance P (10–100 pmol per rat, i.c.v.) caused dose- and time-dependent increases in mean arterial pressure (MAP) ranging from 6±3 to 25±3 mmHg and heart rate (HR) from 63±24 to 133±18 beats/min in conscious rats. The MAP and HR responses peaked at 4 min except at the highest dose of 100 pmol (peak at 5–10 min). [1]
At 25 pmol i.c.v., it produced maximal cardiovascular changes: ΔMAP 15±2 mmHg and ΔHR 120±17 beats/min (day 1). These effects were reproducible when injected once daily over 4 consecutive days. [1] The i.c.v. administration of [Sar9,Met(O2)11]-Substance P (25–100 pmol) dose-dependently increased behavioural activities including face washing, grooming and sniffing during the first 30 min post-injection. The dose of 10 pmol did not significantly affect behavioural activity compared to vehicle. Grooming was observed only with this agonist, not with septide. [1] Intradermal (i.d.) injection of [Sar9,Met(O2)11]-Substance P (0.65–650 pmol) evoked dose-dependent increases in vascular permeability (plasma protein extravasation) in anaesthetized rats. Values ranged from 1.8±0.6 to 9.6±1.6 ng Evans Blue per mg fresh tissue. A significant increase was observed from the dose of 6.5 pmol (P<0.05). [1] |
| Animal Protocol |
For i.c.v. effects on cardiovascular system and motor behaviour: Male Wistar rats (275–300 g) were anaesthetized with sodium pentobarbitone (65 mg/kg i.p.). A polyethylene catheter (PE-20) with a guide cannula was inserted into the right lateral cerebral ventricle (coordinates: 0.6 mm caudal to bregma, 1.3 mm lateral to midline, 5 mm vertical from skull surface) using a stereotaxic apparatus. Two days later, rats were re-anaesthetized and a vascular catheter (PE-50) was inserted into the abdominal aorta through the femoral artery for blood pressure recording. Experiments were conducted 24 h later in conscious, unrestrained rats. [Sar9,Met(O2)11]-Substance P was dissolved in artificial cerebrospinal fluid (aCSF) and administered i.c.v. in a volume of 1 μl followed by a 5 μl flush of aCSF. Doses tested: 10, 25, 65, 100 pmol per rat. Each rat received only one dose on a given day, with increasing doses at 24 h intervals. Behavioural scores (face washing, grooming, sniffing) were summed over 30 min post-injection. [1]
For i.d. effects on vascular permeability: Male Wistar rats were anaesthetized with sodium pentobarbitone (65 mg/kg i.p.). A polyethylene tubing (PE-50) was inserted into the left jugular vein for drug injections. Evans Blue dye (35 mg/kg) was injected i.v. Five minutes later, [Sar9,Met(O2)11]-Substance P was injected i.d. in 100 μl volume into shaved dorsal skin. Doses tested: 0.65, 6.5, 65, 650 pmol per site. Each dose was injected in duplicate. Rats were killed by exsanguination 30 min after i.d. injections. Skin samples were punched out (15 mm diameter), weighed, and incubated in formamide at 50°C for 24 h. Evans Blue content was measured spectrophotometrically at 620 nm. Results were expressed as ng Evans Blue per mg fresh tissue. [1] |
| References | |
| Additional Infomation |
Sar9,Met(O2)11-P substance is a neurokinin-1 receptor agonist. It is an analog of the neuropeptide substance P, which is naturally found in the human body and in the respiratory tracts of many other species.
Drug Indications It has been studied for the treatment of acute respiratory distress syndrome (ARDS) and viral infections. Mechanism of Action The endogenous receptor for substance P is the neurokinin-1 receptor (NK1 receptor, NK1R). Studies have shown that substance P can stimulate cell growth in cell culture[2] and can promote wound healing in human refractory ulcers[3]. In addition, substance P has been shown to reverse diabetes in mice. [Sar9,Met(O2)11]-Substance P is a classical tachykinin NK₁ receptor agonist that was used as a reference to compare with the atypical agonist septide. The study found that while both agonists were equipotent in increasing MAP and HR, they had dissimilar time-courses. [Sar9,Met(O2)11]SP, but not septide, produced grooming behaviour. In vascular permeability assays, [Sar9,Met(O2)11]SP was less potent than septide (septide was more potent at doses 6.5–650 pmol). The NK₁ antagonists LY303870 and RP67580 were significantly more potent in inhibiting septide than [Sar9,Met(O2)11]SP for most centrally mediated responses. The data confirm a distinct pharmacological profile for septide compared to the classical agonist. [1] |
| Molecular Formula |
C64H100N18O15S
|
|---|---|
| Molecular Weight |
1393.6554
|
| Exact Mass |
1392.733
|
| CAS # |
110880-55-2
|
| Related CAS # |
[Sar9,Met(O2)11]-Substance P TFA;2828433-10-7
|
| PubChem CID |
163829
|
| Appearance |
White to off-white solid powder
|
| Density |
1.4±0.1 g/cm3
|
| Index of Refraction |
1.657
|
| LogP |
-1.99
|
| Hydrogen Bond Donor Count |
14
|
| Hydrogen Bond Acceptor Count |
18
|
| Rotatable Bond Count |
42
|
| Heavy Atom Count |
98
|
| Complexity |
2880
|
| Defined Atom Stereocenter Count |
10
|
| SMILES |
CC(C)C[C@@H](C(=O)N[C@@H](CCS(=O)(=O)C)C(=O)N)NC(=O)CN(C)C(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@@H]3CCCN3C(=O)[C@H](CCCCN)NC(=O)[C@@H]4CCCN4C(=O)[C@H](CCCN=C(N)N)N
|
| InChi Key |
OUPXSLGGCPUZJJ-SARDKLJWSA-N
|
| InChi Code |
InChI=1S/C64H100N18O15S/c1-38(2)34-46(57(89)74-42(54(69)86)28-33-98(4,96)97)73-53(85)37-80(3)62(94)48(36-40-18-9-6-10-19-40)79-58(90)47(35-39-16-7-5-8-17-39)78-56(88)43(24-26-51(67)83)75-55(87)44(25-27-52(68)84)76-59(91)50-23-15-32-82(50)63(95)45(21-11-12-29-65)77-60(92)49-22-14-31-81(49)61(93)41(66)20-13-30-72-64(70)71/h5-10,16-19,38,41-50H,11-15,20-37,65-66H2,1-4H3,(H2,67,83)(H2,68,84)(H2,69,86)(H,73,85)(H,74,89)(H,75,87)(H,76,91)(H,77,92)(H,78,88)(H,79,90)(H4,70,71,72)/t41-,42-,43-,44-,45-,46-,47-,48-,49-,50-/m0/s1
|
| Chemical Name |
(2S)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-1-[(2S)-2-amino-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-N-[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-amino-4-methylsulfonyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]-methylamino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1,5-dioxopentan-2-yl]pentanediamide
|
| 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, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
H2O : ~100 mg/mL (~71.75 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 100 mg/mL (71.75 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.7175 mL | 3.5877 mL | 7.1754 mL | |
| 5 mM | 0.1435 mL | 0.7175 mL | 1.4351 mL | |
| 10 mM | 0.0718 mL | 0.3588 mL | 0.7175 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
