 (1-22), human Chemical Structure.png)
Physicochemical Properties
| Molecular Formula | C93H157N27O28S3 |
| Molecular Weight | 2197.60078 |
| Exact Mass | 2196.09 |
| CAS # | 127869-51-6 |
| Related CAS # | C-Type Natriuretic Peptide (CNP) (1-22), human TFA;1966153-17-2 |
| PubChem CID | 16179407 |
| Appearance | White to off-white solid powder |
| LogP | 0.468 |
| Hydrogen Bond Donor Count | 32 |
| Hydrogen Bond Acceptor Count | 35 |
| Rotatable Bond Count | 44 |
| Heavy Atom Count | 151 |
| Complexity | 4490 |
| Defined Atom Stereocenter Count | 17 |
| SMILES | NCCCC[C@H](NC([C@@H](NC([C@@H](NC(CN)=O)CC(C)C)=O)CO)=O)C(NCC(N[C@H]1CSSC[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CCSC)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H]([C@H](CC)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](CC2=CC=CC=C2)NC1=O)=O)=O |
| InChi Key | UHSBKBYWHCBDCJ-DYGWFTAGSA-N |
| InChi Code | InChI=1S/C93H157N27O28S3/c1-12-52(10)76-91(146)104-42-72(127)108-65(44-122)88(143)114-57(26-30-149-11)82(137)118-64(43-121)80(135)103-39-70(125)106-58(31-48(2)3)78(133)101-41-74(129)110-68(92(147)148)47-151-150-46-67(109-73(128)40-100-77(132)54(23-16-18-27-94)111-89(144)66(45-123)119-85(140)59(32-49(4)5)105-69(124)37-96)90(145)116-62(35-53-21-14-13-15-22-53)79(134)102-38-71(126)107-60(33-50(6)7)84(139)112-55(24-17-19-28-95)81(136)115-61(34-51(8)9)86(141)117-63(36-75(130)131)87(142)113-56(83(138)120-76)25-20-29-99-93(97)98/h13-15,21-22,48-52,54-68,76,121-123H,12,16-20,23-47,94-96H2,1-11H3,(H,100,132)(H,101,133)(H,102,134)(H,103,135)(H,104,146)(H,105,124)(H,106,125)(H,107,126)(H,108,127)(H,109,128)(H,110,129)(H,111,144)(H,112,139)(H,113,142)(H,114,143)(H,115,136)(H,116,145)(H,117,141)(H,118,137)(H,119,140)(H,120,138)(H,130,131)(H,147,148)(H4,97,98,99)/t52-,54-,55-,56-,57-,58-,59-,60-,61-,62-,63-,64-,65-,66-,67-,68-,76-/m0/s1 |
| Chemical Name | (4R,10S,16S,19S,22S,28S,31S,34S,37S,40S,43S,49S,52R)-52-[[2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[(2-aminoacetyl)amino]-4-methylpentanoyl]amino]-3-hydroxypropanoyl]amino]hexanoyl]amino]acetyl]amino]-40-(4-aminobutyl)-49-benzyl-28-[(2S)-butan-2-yl]-31-(3-carbamimidamidopropyl)-34-(carboxymethyl)-16,22-bis(hydroxymethyl)-10,37,43-tris(2-methylpropyl)-19-(2-methylsulfanylethyl)-6,9,12,15,18,21,24,27,30,33,36,39,42,45,48,51-hexadecaoxo-1,2-dithia-5,8,11,14,17,20,23,26,29,32,35,38,41,44,47,50-hexadecazacyclotripentacontane-4-carboxylic acid |
| 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) |
Biological Activity
| Targets |
Natriuretic peptide receptor B (NPR-B) agonist No agonist activity for Natriuretic peptide receptor A (NPR-A) No agonist activity for growth hormone secretagogue receptor 1a (GHS-R1a) [1] |
| ln Vitro |
In CHO cells expressing human NPR-B, C-Type Natriuretic Peptide (CNP) (1-22), human (0.01, 0.1, 1,10, 100, 1000 nM), dose-dependently enhances cGMP synthesis [1]. CNP(1-22) increased cyclic guanosine monophosphate (cGMP) production in Chinese hamster ovarian (CHO) cells stably expressing human NPR-B in a concentration-dependent manner, demonstrating its agonist activity for NPR-B. [1] CNP(1-22) did not increase cGMP production in CHO cells stably expressing human NPR-A, indicating no agonist activity for NPR-A. [1] CNP(1-22) did not increase intracellular Ca2+ concentration in CHO cells stably expressing rat GHS-R1a, indicating no agonist activity for GHS-R1a. [1] |
| ln Vivo |
C-type natriuretic peptide (1-22) single intravenous injection PK parameters of CNP immunoreactivity in humans [1]: Dose (nM/kg) AUC0-∞ (pM·min/mL) MRT0-∞ (min) T1/2 (min) CLtot (mL/min/kg) Vdss (mL/kg) 20 320±54 1.02±0.18 1.42±0.45 63.9±11.9 64.2±5.1 CNP) (1-22), posthuman CNP PK parameters of immunoreactivity: Dose (nM/kg) Cmax (pM/mL) Tmax (min) AUC0-∞ (pM·min/mL) MRT0-∞ (min) T1/2 (min) BA (%) 50 9.02±3.74 5.0±0.0 152±73 13.9±3.4 10.0±5.0 19±9 Each value represents the mean ± SD of three rats. Mean residence time (MRT), total clearance (CLtot), half-life (T1/2), and bioavailability (BA). When administered to humans at a concentration of 2 nM for 24 and 48 hours, C-type natriuretic peptide (CNP) (1-22) increases the intensity of convulsions brought on by microtoxins [3]. Single subcutaneous (sc) bolus injection of CNP(1-22) at 1600 nmol/kg in mice increased cGMP concentrations in plasma and auricular cartilage, but the levels were lower compared to the novel analog ASB20123 at a much lower dose. [1] Repeated sc administration of CNP(1-22) to mice under the conditions tested showed no significant effect on skeletal growth, unlike its chimeric derivatives. [1] It was reported that exogenous CNP(1-22) improved endochondral ossification and accelerated bone growth in mice, but only after constant intravenous infusion at a large dose. [1] |
| Enzyme Assay |
The agonist activity of CNP(1-22) for human NPR-A and NPR-B was evaluated using CHO cells stably expressing these receptors. The test compound was added to cells in duplicate and incubated for 15 minutes. Cells were then lysed, and the cGMP concentration in the lysate was determined using a competitive enzyme-linked immunosorbent assay (ELISA). [1] The agonist activity for rat GHS-R1a was evaluated using CHO cells stably expressing this receptor. Changes in intracellular Ca2+ concentration were measured using a fluorescence-based calcium assay kit. [1] |
| Cell Assay |
The in vitro receptor specificity and potency of CNP(1-22) were assessed using cell-based assays. For NPR-A and NPR-B activity, CHO cells expressing the respective receptors were treated with the peptide. After incubation, cellular cGMP levels were quantified via ELISA as a measure of receptor activation. [1] For GHS-R1a activity, CHO cells expressing rat GHS-R1a were treated with the peptide, and receptor activation was assessed by measuring changes in intracellular Ca2+ concentration using a fluorescent dye. [1] |
| Animal Protocol |
Pharmacokinetic (PK) Study in Rats: Male Sprague Dawley (SD) rats (7 or 8 weeks old) were anesthetized. A cannula was inserted into the jugular vein for blood sampling. CNP(1-22) was administered as a single intravenous (iv) injection (20 nmol/kg) or subcutaneous (sc) injection (50 nmol/kg) at a dose volume of 1 mL/kg. Blood samples were collected at designated times via the cannula into tubes containing protease inhibitor and anticoagulant. Plasma was separated by centrifugation. CNP immunoreactivity in plasma was determined by radioimmunoassay (RIA). Plasma cGMP concentration was also determined by RIA. [1] cGMP Production in Mouse Auricular Cartilage: Six-week-old ICR male mice received a single sc bolus injection of CNP(1-22) at 1600 nmol/kg or vehicle. At designated times, mice were anesthetized, blood was collected from the inferior vena cava for plasma, and a portion of the ear auricle was isolated. The auricular cartilage was separated, homogenized in perchloric acid, and processed. cGMP concentrations in plasma and cartilage homogenates were measured using enzyme immunoassay (EIA) kits. [1] In Vivo Pharmacological Study in Mice: Three-week-old juvenile female ICR mice received daily sc bolus injections of vehicle (control) for 8 weeks (the study primarily evaluated ASB20123, with CNP(1-22) used as a reference in earlier studies showing lack of efficacy under similar repeated dosing regimens). Body weight, body length, and tail length were measured weekly. [1] |
| ADME/Pharmacokinetics |
In anesthetized rats, after a single intravenous (iv) dose of 20 nmol/kg, CNP(1-22) had an AUC0-∞ of 320 ± 54 pmol·min/mL, a mean residence time (MRT0-∞) of 1.02 ± 0.18 min, a half-life (T1/2) of 1.42 ± 0.45 min, a total clearance (CL) of 63.9 ± 11.9 mL/min/kg, and a volume of distribution at steady state (Vdss) of 64.2 ± 5.1 mL/kg. [1] After a single subcutaneous (sc) dose of 50 nmol/kg in anesthetized rats, CNP(1-22) had a Cmax of 9.02 ± 3.74 pmol/mL, a Tmax of 5.0 ± 0.0 min, an AUC0-∞ of 152 ± 73 pmol·min/mL, an MRT0-∞ of 13.9 ± 3.4 min, a T1/2 of 10.0 ± 5.0 min, and a bioavailability (BA) of 19 ± 9%. [1] CNP(1-22) was rapidly cleared from the circulation following exogenous administration. [1] The plasma cGMP concentration increased after CNP(1-22) dosing but returned to basal levels relatively quickly compared to its analog. [1] |
| Toxicity/Toxicokinetics |
The literature [1] mentions that if CNP(1-22) is administered at high doses, it might cause a decrease in systemic vascular resistance and blood pressure in patients, indicating a potential risk of hypotension. [1] |
| References |
[1]. ASB20123: A novel C-type natriuretic peptide derivative for treatment of growth failure and dwarfism. PLoS One. 2019 Feb 22;14(2):e0212680. [2]. Circulating C-type natriuretic peptide is increased in orthotopic cardiac transplant recipients and associated with cardiac allograft vasculopathy. Clin Sci (Lond). 2000 Nov;99(5):467-72. [3]. ANP(1-28), BNP(1-32) and CNP(1-22) increase the severity of picrotoxin-kindled seizure syndrome in rats. Life Sci. 1993;52(3):PL19-24. |
| Additional Infomation |
A PEPTIDE of 22 amino acids, derived mainly from cells of VASCULAR ENDOTHELIUM. It is also found in the BRAIN, major endocrine glands, and other tissues. It shares structural homology with ATRIAL NATRIURETIC FACTOR. It has vasorelaxant activity thus is important in the regulation of vascular tone and blood flow. Several high molecular weight forms containing the 22 amino acids have been identified. CNP(1-22) is a 22-amino acid peptide and is a major endogenous molecular form of CNP found in plasma. [1] Exogenous CNP(1-22) is rapidly cleared from the circulation, which limits its therapeutic efficacy. [1] CNP(1-22) and all natriuretic peptides can induce diuresis and hypotension in the circulation. High-dose administration carries a risk of reducing systemic vascular resistance and blood pressure. [1] The CNP/NPR-B signaling pathway is a pivotal physiological stimulator of endochondral bone growth, making CNP and its analogs potential therapeutic candidates for growth failure conditions like achondroplasia. [1] |
Solubility Data
| Solubility (In Vitro) | H2O : ~50 mg/mL (~22.75 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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.4550 mL | 2.2752 mL | 4.5504 mL | |
| 5 mM | 0.0910 mL | 0.4550 mL | 0.9101 mL | |
| 10 mM | 0.0455 mL | 0.2275 mL | 0.4550 mL |