| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 50mg | |||
| Other Sizes |
| Targets |
The primary target of A 71915 is the natriuretic peptide receptor A (NPRA), also known as guanylyl cyclase-A. This receptor is a transmembrane protein that possesses intrinsic guanylyl cyclase activity. Upon binding of its natural ligands, ANP or BNP, NPRA catalyzes the production of cyclic GMP (cGMP), a second messenger that mediates various physiological effects including vasodilation, natriuresis, and diuresis. A 71915 acts as a competitive antagonist, binding to the receptor and blocking the binding of ANP and BNP, thereby inhibiting the production of cGMP.
|
|---|---|
| ln Vitro |
For the circulating GMP assay, A 71915 binds to neuroblastoma NB-OK-1 cells. For circulating GMP synthesis, A 71915 causes a rightward change in the ANP dose-response curve [1].
In vitro, A 71915 demonstrates potent antagonist activity at NPRA. It has a pKi of 9.18 for binding to the receptor. The compound displaces [¹²⁵I]-ANP in a dose-dependent manner with a Ki of 0.65 nM. In functional assays, A 71915 antagonizes ANP-induced cGMP production in NB-OK-1 cells, with a pA2 value of 9.48. These data confirm the compound's high potency and efficacy as an NPRA antagonist. |
| ln Vivo |
A71915 (5 μl; intramuscular injection; male CD-1 mice weighing 25–30 g) had an effect on scratching produced by BNP (1 nmol) and GRP (0.1 nmol) [2]. A 71915 (30 μg/kg/day) reduces blood pressure and inhibits NS-398 [3].
In vivo data for A 71915 are not extensively reported in the available literature. As a potent NPRA antagonist, the compound has potential for in vivo applications in studying the role of the natriuretic peptide system in cardiovascular and renal function. By blocking NPRA, A 71915 would be expected to antagonize the effects of ANP and BNP, leading to increased blood pressure and reduced natriuresis and diuresis. However, specific in vivo efficacy data, including animal models, dosing regimens, and pharmacokinetic-pharmacodynamic relationships, are not detailed in the available sources. |
| Enzyme Assay |
In vitro receptor binding assays for A 71915 typically involve measuring its displacement of a radiolabeled ligand from NPRA. Membrane preparations expressing NPRA are incubated with [¹²⁵I]-labeled ANP and varying concentrations of A 71915. After incubation, bound and free radioligands are separated, and the radioactivity is measured. The Ki for displacement is calculated from the competition curve. Functional assays measure the compound's ability to inhibit ANP-stimulated cGMP production.
|
| Cell Assay |
Cellular assays for A 71915 are performed in cells expressing NPRA, such as NB-OK-1 cells. Cells are treated with ANP or BNP in the presence or absence of A 71915, and the production of cGMP is measured using an immunoassay. The compound's ability to inhibit cGMP production is used as a measure of its antagonist activity. The pA2 value, a measure of antagonist potency, is calculated from the dose-response curves.
|
| Animal Protocol |
Animal/Disease Models: Rat (male SD (SD (Sprague-Dawley))); body weight 150-180 g [3]
Doses: 30 μg/kg/day; infusion for 3 weeks Dosing: via mini-osmotic pump Experimental Results: A 71915 (30 μg/kg/ days) pretreatment attenuated the inhibitory effect of NS-398 on blood pressure. In vivo animal studies with A 71915 are not extensively documented in the available literature. Based on its antagonism of NPRA, potential in vivo models could include rodent models of hypertension or heart failure. In such studies, A 71915 would be administered intravenously or intraperitoneally, and blood pressure, heart rate, and urine output would be measured. However, specific protocols are not detailed in the available sources. |
| ADME/Pharmacokinetics |
Pharmacokinetic data for A 71915 are not extensively reported. The compound is a peptide or peptide-like molecule (its exact structure is not specified in the available literature). As such, it would likely have poor oral bioavailability and would require parenteral administration for in vivo studies. However, detailed pharmacokinetic parameters are not available in the literature for this research compound.
|
| Toxicity/Toxicokinetics |
Comprehensive toxicology data for A 71915 are not extensively reported. The compound is classified as a research-use-only chemical and is not intended for human consumption. As an antagonist of the natriuretic peptide system, it may have effects on blood pressure and fluid balance that could contribute to toxicity. Specific toxicological data, including acute toxicity, genotoxicity, and target organ effects, are not reported in the available literature.
|
| References |
|
| Additional Infomation |
atrial natriuretic factor receptor antagonists
A 71915 is a research-grade compound not approved for clinical use. Its primary application is as a pharmacological tool for studying the natriuretic peptide system. The compound is used to investigate the role of NPRA and its ligands (ANP and BNP) in cardiovascular and renal physiology. It is also used to study the therapeutic potential of modulating the natriuretic peptide system in diseases such as hypertension, heart failure, and kidney disease. |
| Molecular Formula |
C69H116N26O15S2
|
|---|---|
| Molecular Weight |
1613.97
|
| Exact Mass |
1612.855
|
| CAS # |
132956-87-7
|
| Related CAS # |
A-71915 TFA
|
| PubChem CID |
25083020
|
| Appearance |
White to off-white solid powder
|
| Density |
1.5±0.1 g/cm3
|
| Index of Refraction |
1.698
|
| LogP |
-5.73
|
| Hydrogen Bond Donor Count |
22
|
| Hydrogen Bond Acceptor Count |
22
|
| Rotatable Bond Count |
27
|
| Heavy Atom Count |
112
|
| Complexity |
3310
|
| Defined Atom Stereocenter Count |
13
|
| SMILES |
CC[C@H](C)[C@H]1C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N2CC3=CC=CC=C3C[C@@H]2C(=O)NCC(=O)N[C@@H]([C@H](SSC[C@@H](C(=O)N[C@H](C(=O)NCC(=O)NCC(=O)N[C@@H](C(=O)N1)CCCN=C(N)N)CC4CCCCC4)NC(=O)[C@H](CCCN=C(N)N)N)CCCN=C(N)N)C(=O)N)[C@@H](C)CC)CCCN=C(N)N)CC(=O)O
|
| InChi Key |
TZQXLCWSYQJGKV-YGLLJKSHSA-N
|
| InChi Code |
InChI=1S/C69H116N26O15S2/c1-5-36(3)53-64(109)90-45(30-52(99)100)61(106)88-43(22-14-26-82-68(76)77)60(105)94-54(37(4)6-2)65(110)95-34-40-19-11-10-18-39(40)29-47(95)63(108)86-33-51(98)92-55(56(71)101)48(23-15-27-83-69(78)79)112-111-35-46(91-57(102)41(70)20-12-24-80-66(72)73)62(107)89-44(28-38-16-8-7-9-17-38)58(103)85-31-49(96)84-32-50(97)87-42(59(104)93-53)21-13-25-81-67(74)75/h10-11,18-19,36-38,41-48,53-55H,5-9,12-17,20-35,70H2,1-4H3,(H2,71,101)(H,84,96)(H,85,103)(H,86,108)(H,87,97)(H,88,106)(H,89,107)(H,90,109)(H,91,102)(H,92,98)(H,93,104)(H,94,105)(H,99,100)(H4,72,73,80)(H4,74,75,81)(H4,76,77,82)(H4,78,79,83)/t36-,37-,41-,42+,43-,44-,45-,46-,47+,48+,53-,54-,55-/m0/s1
|
| Chemical Name |
L-Cysteinamide, L-arginyl-L-cysteinyl-3-cyclohexyl-L-alanylglycylglycyl-L-arginyl-L-isoleucyl-L-alpha-aspartyl-L-arginyl-L-isoleucyl-D-1,2,3,4-tetrahydro-3-isoquinolinecarbonyl-L-arginyl-, cyclic (2-13)-disulfide
|
| Synonyms |
A-71915 A71915A 71915
|
| 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 (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)
|
| Solubility (In Vitro) |
H2O : ≥ 50 mg/mL (~30.98 mM)
|
|---|---|
| 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 | 0.6196 mL | 3.0980 mL | 6.1959 mL | |
| 5 mM | 0.1239 mL | 0.6196 mL | 1.2392 mL | |
| 10 mM | 0.0620 mL | 0.3098 mL | 0.6196 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
