| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
Neurokinin‑2 (NK2) receptor. GR 64349 has high affinity for NK2 (Ki ~ 1‑3 nM) with >1000‑fold selectivity over NK1 and NK3 receptors. It is a full agonist. NK2 receptors are primarily found in peripheral tissues (smooth muscle of gastrointestinal tract, bladder, airways) and to a lesser extent in the CNS.
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| ln Vitro |
In vitro, GR 64349 induces contraction of isolated smooth muscle preparations, such as rat colon, rabbit bladder, and guinea pig trachea, with EC50 values in the low nanomolar range (1‑10 nM). The contraction is blocked by NK2 antagonists (e.g., SR 48968). It also stimulates inositol phosphate accumulation in cells expressing NK2 receptors.
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| ln Vivo |
In vivo, GR 64349 (10‑100 microg/kg i.v. or i.p.) produces bronchoconstriction in guinea pigs, increases urinary bladder contractions in rats, and induces colonic motility. These effects are NK2‑mediated and are blocked by NK2 antagonists. GR 64349 also potentiates nociceptive responses in inflammatory pain models, suggesting a pro‑nociceptive role of NK2.
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| Enzyme Assay |
Use CHO cells expressing human NK2 receptor. Prepare membranes (20 microg protein). Incubate with 0.5 nM [¹2⁵I]‑neurokinin A and GR 64349 (0.01 nM‑10 microM) in 50 mM Tris‑HCl pH 7.4 containing 4 mM MnCl2, 0.1% BSA, and protease inhibitors for 60 min at RT. Non‑specific: 1 microM neurokinin A. Filter through GF/B (0.5% PEI), wash, count gamma. Ki = 1‑3 nM.
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| Cell Assay |
Seed CHO‑NK2 cells in 96‑well plates (40,000/well) in DMEM/10% FBS for 48 h. Load with Fluo‑4 AM (2.5 microM) for 60 min. Wash, add GR 64349 (0.01 nM‑10 microM) and measure calcium fluorescence. For inositol phosphate accumulation: label cells with 1 microCi/mL [3H]‑myo‑inositol for 24 h, wash, add LiCl (10 mM) and GR 64349 for 30 min, extract, quantify IPs. EC50 from Ca2+ flux ~1‑5 nM.
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| Animal Protocol |
Use male Dunkin‑Hartley guinea pigs (300‑500 g) for bronchoconstriction. Anesthetize, intubate, measure airway resistance. Administer GR 64349 (10‑100 microg/kg i.v.) and record peak increase in airway resistance. Pre‑treat with NK2 antagonist (e.g., SR 48968, 1 mg/kg i.v.) 5 min before to block. Also rat urinary bladder: anesthetized rat, insert bladder catheter, infuse saline, record intravesical pressure. GR 64349 (30‑100 microg/kg i.v.) increases contraction frequency.
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| ADME/Pharmacokinetics |
GR 64349 is a peptide, thus not orally bioavailable. t½ after i.v. in rats ~10‑20 min due to rapid proteolysis. Cleared by peptidases in plasma and tissues. Does not cross BBB significantly. Usually administered by i.v., i.p., or s.c. in research. High volume of distribution due to peripheral NK2 binding.
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| Toxicity/Toxicokinetics |
Low systemic toxicity at doses up to 300 microg/kg i.v. in rodents/guinea pigs. At high doses (>1 mg/kg), excessive bronchoconstriction and hypotension may cause mortality. No chronic toxicity data. As a peptide, allergenicity possible. Research use only, not for human therapy.
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| References |
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| Additional Infomation |
NK2 receptor agonist. Used to study NK2‑mediated smooth muscle contraction, inflammation, and visceral pain. Not clinically developed. CAS 137593‑52‑3. Store lyophilized at −20degC. Often used in combination with NK1 and NK3 tools to dissect tachykinin pathways.
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| Molecular Formula |
C42H68N10O11S
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|---|---|
| Molecular Weight |
921.11
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| Exact Mass |
920.479
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| CAS # |
137593-52-3
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| Related CAS # |
GR 64349 TFA
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| PubChem CID |
5311135
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| Appearance |
White to off-white solid powder
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| Density |
1.31g/cm3
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| Boiling Point |
1342.8ºC at 760mmHg
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| Flash Point |
765.9ºC
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| LogP |
1.986
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| Hydrogen Bond Donor Count |
11
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| Hydrogen Bond Acceptor Count |
14
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| Rotatable Bond Count |
29
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| Heavy Atom Count |
64
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| Complexity |
1600
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| Defined Atom Stereocenter Count |
7
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| SMILES |
CC(C)C[C@@H](C(=O)N[C@@H](CCSC)C(=O)N)N1CCC(C1=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCCN)N
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| InChi Key |
HVUNRXRFMQDMBO-BPZYSUIOSA-N
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| InChi Code |
InChI=1S/C42H68N10O11S/c1-23(2)19-32(40(61)46-27(35(45)56)15-18-64-5)52-17-14-28(42(52)63)47-41(62)34(24(3)4)51-38(59)29(20-25-11-7-6-8-12-25)49-39(60)31(22-53)50-37(58)30(21-33(54)55)48-36(57)26(44)13-9-10-16-43/h6-8,11-12,23-24,26-32,34,53H,9-10,13-22,43-44H2,1-5H3,(H2,45,56)(H,46,61)(H,47,62)(H,48,57)(H,49,60)(H,50,58)(H,51,59)(H,54,55)/t26-,27-,28?,29-,30-,31-,32-,34-/m0/s1
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| Chemical Name |
(3S)-4-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[1-[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]-2-oxopyrrolidin-3-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-[[(2S)-2,6-diaminohexanoyl]amino]-4-oxobutanoic 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, 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) |
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 | 1.0856 mL | 5.4282 mL | 10.8565 mL | |
| 5 mM | 0.2171 mL | 1.0856 mL | 2.1713 mL | |
| 10 mM | 0.1086 mL | 0.5428 mL | 1.0856 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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