| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 100mg | |||
| Other Sizes |
| Targets |
Substance P TFA specifically and selectively binds to the neurokinin-1 receptor (NK1R), a G protein-coupled receptor (GPCR) broadly distributed on neurons and immune cells. It exhibits high binding affinity for NK1 with a Ki value of 0.14 nM, while displaying much lower affinity for NK3 (Ki = 300 nM). Upon ligand binding, NK1R undergoes endocytosis and recycling, which is associated with receptor desensitization and resensitization. The NK1 receptor is recognized as the primary endogenous receptor for substance P.
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| ln Vitro |
Neurokinin 1 receptor (NK1-R)-mediated desensitization and resensitization of neuropeptide substance P (SP), which may be connected to NK1-R endocytosis and recycling. The same protein-immunoreactive vesicles that internalize SP and NK1-R are subsequently divided into distinct compartments. In early endosomes and on the cell surface, SP is undamaged; however, it gradually deteriorates in perinuclear vesicles. In acidified endosomes, SP causes the SP/NK1-R complex to dissociate. NK1-R is recycled to the cell surface while SP is broken down. In transfected epithelial cells, SP detects the internalization of NK1-R [1].
In vitro studies demonstrate that Substance P TFA activates endothelial cells via NK1 receptor binding, leading to thromboxane A2 release and increased lymphatic constriction frequency. It potently stimulates intracellular calcium mobilization and signaling cascades in NK1R-expressing cell lines. The neuropeptide induces proliferation, migration, and cytokine production in various cell types, including immune cells and fibroblasts, highlighting its role in inflammation and tissue remodeling. |
| ln Vivo |
In vivo, Substance P TFA induces pain through NK1 receptors following noxious peripheral stimulation. In a rat hindpaw model of inflammation, NK1 receptor internalization occurs in a greater number of spinal cord neurons following mechanical or non-noxious stimuli, indicating the involvement of substance P in inflammation and hyperalgesia. The peptide also plays roles in depression, anxiety, seizures, emesis, and regulation of blood pressure and heart rate.
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| Enzyme Assay |
For receptor binding affinity assays, competition binding experiments are performed using human NK1 receptors expressed in CHO (Chinese hamster ovary) cells. Cell membrane homogenates (10-50 microg protein) are incubated with 0.1-0.5 nM [3H]Substance P in binding buffer (50 mM Tris-HCl, pH 7.4, 3 mM MnCl2, 0.1% BSA). Increasing concentrations of unlabeled Substance P TFA are added to compete with the radioligand. After 60 minutes at 25degC, bound radioactivity is separated by vacuum filtration through GF/B filters and quantified by scintillation counting. Ki values are calculated by nonlinear regression.
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| Cell Assay |
Functional cellular assays are performed using NK1R-expressing cell lines, such as CHO-NK1R or U-373 MG human astrocytoma cells. Cells are seeded in 96-well plates and loaded with a calcium-sensitive fluorescent dye (e.g., Fluo-4-AM). After washing, varying concentrations of Substance P TFA are added, and intracellular calcium flux (reflecting Gq-coupled receptor activation) is measured using a fluorescence plate reader. The half-maximal effective concentration for calcium mobilization is determined as a measure of NK1R agonistic potency.
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| Animal Protocol |
For in vivo pharmacological studies, Substance P TFA is typically administered by intracerebroventricular (i.c.v.) injection, intrathecal injection, or intravenous infusion in rodent models. Male Sprague-Dawley rats (250-350 g) are anesthetized and placed in a stereotaxic frame for i.c.v. injection. Substance P TFA is dissolved in artificial cerebrospinal fluid and injected over 1-2 minutes. Behavioral responses including pain-related behaviors, grooming, or scratching are monitored post-injection. Alternatively, NK1R internalization in spinal cord sections is assessed by immunohistochemistry following peripheral inflammation induction.
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| ADME/Pharmacokinetics |
As an endogenous peptide neurotransmitter, Substance P TFA is rapidly degraded by proteolytic enzymes in vivo, such as neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE), resulting in a short biological half-life (typically minutes). When administered into the central nervous system, the peptide exerts potent but transient pharmacological effects. Its TFA salt form enhances aqueous solubility, facilitating formulation for injection and infusion studies. Systemic bioavailability is very low due to extensive enzymatic degradation.
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| Toxicity/Toxicokinetics |
As an endogenous signaling molecule, Substance P TFA exhibits a favorable safety profile with no significant off-target toxicity at physiological concentrations. Synthetic Substance P TFA is used exclusively for research applications; no clinical toxicology studies have been conducted for this form. At high pharmacological doses, it may induce effects such as hypotension, increased vascular permeability, and excessive salivation, mediated by NK1 receptor activation. The peptide is generally well-tolerated in animal studies at the doses used for receptor pharmacology research.
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| References | |
| Additional Infomation |
Substance P TFA (CAS# 148470-19-3) is a research-grade peptide widely employed as a reference agonist for NK1 receptor studies. It serves as a standard for drug discovery programs targeting NK1 antagonism for conditions including pain, migraine, emesis, and depression. While substance P itself is an endogenous ligand, its TFA salt is a research tool only and is not approved for therapeutic use. NK1 receptor antagonists (aprepitant) have been clinically approved as antiemetics. Substance P TFA has a molecular weight of 1461.67 and an amino acid sequence of RPKPQQFFGLM-NH2.
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| Molecular Formula |
C65H99F3N18O15S
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|---|---|
| Molecular Weight |
1461.65338349342
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| Exact Mass |
1460.721
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| CAS # |
148470-19-3
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| Related CAS # |
Substance P;33507-63-0
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| PubChem CID |
137700174
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
16
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| Hydrogen Bond Acceptor Count |
22
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| Rotatable Bond Count |
42
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| Heavy Atom Count |
102
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| Complexity |
2700
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| Defined Atom Stereocenter Count |
10
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| SMILES |
C(F)(F)(F)C(=O)O.C(N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@H](C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N)CCSC)CC1C=CC=CC=1)CC1C=CC=CC=1)(=O)[C@H](CCCCN)NC([C@@H]1CCCN1C(=O)[C@@H](N)CCCNC(N)=N)=O
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| InChi Key |
HJUBUMANGKVTGH-HDKZLILXSA-N
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| InChi Code |
InChI=1S/C63H98N18O13S.C2HF3O2/c1-37(2)33-45(57(89)74-41(53(68)85)27-32-95-3)73-52(84)36-72-54(86)46(34-38-15-6-4-7-16-38)78-58(90)47(35-39-17-8-5-9-18-39)79-56(88)42(23-25-50(66)82)75-55(87)43(24-26-51(67)83)76-59(91)49-22-14-31-81(49)62(94)44(20-10-11-28-64)77-60(92)48-21-13-30-80(48)61(93)40(65)19-12-29-71-63(69)70;3-2(4,5)1(6)7/h4-9,15-18,37,40-49H,10-14,19-36,64-65H2,1-3H3,(H2,66,82)(H2,67,83)(H2,68,85)(H,72,86)(H,73,84)(H,74,89)(H,75,87)(H,76,91)(H,77,92)(H,78,90)(H,79,88)(H4,69,70,71);(H,6,7)/t40-,41-,42-,43-,44-,45-,46-,47-,48-,49-;/m0./s1
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| 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-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1,5-dioxopentan-2-yl]pentanediamide;2,2,2-trifluoroacetic 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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), 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)
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| Solubility (In Vitro) |
H2O : ~100 mg/mL (~68.42 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 50 mg/mL (34.21 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 | 0.6842 mL | 3.4208 mL | 6.8416 mL | |
| 5 mM | 0.1368 mL | 0.6842 mL | 1.3683 mL | |
| 10 mM | 0.0684 mL | 0.3421 mL | 0.6842 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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