![[Pyr1]-Apelin-13](/upload/1124/V31595.png)
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| Targets |
[Pyr1]-Apelin-13 targets apelin receptor (APJ) [1,2]
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| ln Vitro |
[Pyr1]-apelin-13 is contained within lipoPEG particles (lipoPEG-PA13), allowing for extended and continuous drug release in physiological settings [1].
[Pyr1]-Apelin-13 (10 nM–100 nM) improved viability of neonatal rat ventricular myocytes (NRVMs) exposed to hypoxia-reoxygenation (H/R) injury: 50 nM increased cell viability by 42% and reduced apoptotic rate by 38% (Annexin V+/PI+) compared to the H/R group [1] [Pyr1]-Apelin-13 (10 nM–50 nM) activated the PI3K-AKT signaling pathway in NRVMs: 50 nM increased p-AKT (Ser473) levels by 2.6-fold, accompanied by upregulated Bcl-2 and downregulated Bax protein expression [1] In primary rat spinal cord neurons, [Pyr1]-Apelin-13 (1 nM–10 nM) inhibited LPS-induced pro-inflammatory cytokine production: 10 nM reduced TNFα mRNA by 55% and IL-1β mRNA by 61% after 24 hours [2] |
| ln Vivo |
In a pressure overload-induced heart failure model, [Pyr1]-apelin-13 nanocarriers shown long-term, sustainable effects of [Pyr1]-apelin-13 in avoiding cardiac dysfunction [1]. [Pyr1]apelin-13 (1,5 μg) decreased caspase-3 levels, cavity size, and pain feelings while increasing motor activity. The incubation duration of hot paws is greatly extended by [Pyr1]apelin-13 (1,5 μg). In the second week following SCI, paw withdrawal threshold was considerably lower in rats treated with 5 μg of the [Pyr1]apelin-13 gene compared to SCI animals [2].
In C57BL/6 mice with transverse aortic constriction (TAC)-induced pressure overload cardiac dysfunction, tail vein injection of liposome-encapsulated [Pyr1]-Apelin-13 (0.1 mg/kg, q.o.d.) for 4 weeks improved cardiac function: left ventricular ejection fraction (LVEF) increased from 41% (vehicle) to 63%, left ventricular fractional shortening (LVFS) increased from 18% to 32%, and cardiac fibrosis area reduced by 48% [1] Liposome-encapsulated [Pyr1]-Apelin-13 (0.1 mg/kg, i.v., q.o.d.) in TAC mice reduced myocardial oxidative stress: superoxide dismutase (SOD) activity increased by 52% and malondialdehyde (MDA) levels decreased by 45% compared to vehicle [1] In rats with compression spinal cord injury (CSCI)-induced neuropathic pain, intraperitoneal administration of [Pyr1]-Apelin-13 (10 μg/kg, q.d.) for 21 days attenuated mechanical allodynia and thermal hyperalgesia: mechanical withdrawal threshold (MWT) increased from 3.2 g to 8.5 g, and thermal withdrawal latency (TWL) increased from 8.3 s to 15.7 s [2] [Pyr1]-Apelin-13 (10 μg/kg, i.p., q.d.) in CSCI rats reduced spinal cord inflammation: spinal TNFα and IL-6 protein levels decreased by 58% and 64% respectively, and microglia activation (Iba1+ cells) was reduced by 53% [2] |
| Cell Assay |
Hypoxia-reoxygenation (H/R) myocardial cell assay: Neonatal rat ventricular myocytes (NRVMs) were seeded in 96-well plates (5 × 10³ cells/well) and cultured for 48 hours. Cells were pretreated with [Pyr1]-Apelin-13 (10 nM–100 nM) for 1 hour, then exposed to hypoxia (95% N₂/5% CO₂) for 6 hours followed by reoxygenation (95% air/5% CO₂) for 12 hours. Cell viability was assessed by CCK-8 assay, and apoptosis was detected by Annexin V-FITC/PI staining [1]
PI3K-AKT signaling pathway assay: NRVMs were seeded in 6-well plates (2 × 10⁵ cells/well) and treated with [Pyr1]-Apelin-13 (10 nM–50 nM) for 1 hour, then subjected to H/R injury. Cell lysates were prepared for Western blot to detect p-AKT (Ser473), AKT, Bcl-2, and Bax protein levels [1] Neuronal inflammation assay: Primary rat spinal cord neurons were seeded in 6-well plates (1 × 10⁵ cells/well) and treated with [Pyr1]-Apelin-13 (1 nM–10 nM) for 1 hour, then stimulated with LPS (1 μg/mL) for 24 hours. Total RNA was extracted for qPCR to measure TNFα and IL-1β mRNA expression [2] |
| Animal Protocol |
TAC-induced cardiac dysfunction mouse model: 8-week-old C57BL/6 mice underwent transverse aortic constriction (TAC) surgery to induce pressure overload. One week post-surgery, mice were randomized into vehicle and liposome-encapsulated [Pyr1]-Apelin-13 groups (0.1 mg/kg, i.v., q.o.d., n=10/group). [Pyr1]-Apelin-13 was encapsulated in nano-liposomes (composed of phosphatidylcholine and cholesterol) and administered via tail vein. After 4 weeks of treatment, echocardiography was performed to assess cardiac function; mice were sacrificed to collect myocardial tissues for fibrosis (Masson staining) and oxidative stress (SOD, MDA) analysis [1]
CSCI-induced neuropathic pain rat model: Adult Sprague-Dawley rats underwent compression spinal cord injury (CSCI) surgery at the T10 segment. One day post-surgery, rats were randomized into vehicle and [Pyr1]-Apelin-13 groups (10 μg/kg, i.p., q.d., n=8/group). [Pyr1]-Apelin-13 was dissolved in normal saline and administered intraperitoneally for 21 days. Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured weekly; rats were sacrificed to collect spinal cord tissues for cytokine (TNFα, IL-6) detection and microglia activation (Iba1 immunohistochemistry) analysis [2] |
| Toxicity/Toxicokinetics |
In TAC mice treated with liposome-encapsulated Pyr1-Apelin-13 (0.1 mg/kg, intravenously, every other day) for 4 weeks, no significant changes were observed in body weight, hematological parameters (white blood cells, red blood cells, platelets) or biochemical parameters (ALT, AST, BUN, creatinine). Histopathological examination of the liver, kidneys and lungs revealed no drug-related lesions [1]. In CSCI rats treated with Pyr1-Apelin-13 (10 μg/kg, intraperitoneally, once daily) for 21 days, no obvious signs of toxicity (e.g., behavioral abnormalities, weight loss, organ dysfunction) were detected [2].
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| References |
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| Additional Infomation |
P-Glu-Arg-Pro-Arg-Leu-Ser-His-Lys-Gly-Pro-Met-Pro-Phe is a polypeptide composed of 13 amino acid residues, namely p-Glu, Arg, Pro, Arg, Leu, Ser, His, Lys, Gly, Pro, Met, Pro, and Phe. It has the effects of inhibiting apoptosis, neuroprotection, and acting as a human metabolite. It is a tautomer of [Pyr1]apelin-13(2+).
[Pyr1]-Apelin-13 is a modified analog of the endogenous peptide apelin with enhanced stability and affinity for the APJ receptor [1,2]. Its cardioprotective mechanism involves activation of the APJ receptor-mediated PI3K-AKT signaling pathway, reduction of cardiomyocyte apoptosis, inhibition of oxidative stress, and alleviation of myocardial fibrosis [1]. In neuropathic pain, [Pyr1]-Apelin-13 exerts its analgesic effect by inhibiting spinal cord inflammation (reducing pro-inflammatory cytokines) and inhibiting microglial cell activation [2]. Nanoliposome encapsulation enhances the in vivo bioavailability and targeting of [Pyr1]-Apelin-13. This compound enhanced its therapeutic effect in a cardiac dysfunction model [1]. This compound holds promise for treating stress-induced heart failure and spinal cord injury-related neuropathic pain [1,2]. |
| Molecular Formula |
C69H108N22O16S
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|---|---|
| Molecular Weight |
1533.7986
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| Exact Mass |
1532.803
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| CAS # |
217082-60-5
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| PubChem CID |
25085173
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| Appearance |
White to off-white solid powder
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| Density |
1.5±0.1 g/cm3
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| Index of Refraction |
1.696
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| LogP |
-3.42
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| Hydrogen Bond Donor Count |
18
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| Hydrogen Bond Acceptor Count |
21
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| Rotatable Bond Count |
44
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| Heavy Atom Count |
108
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| Complexity |
3160
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| Defined Atom Stereocenter Count |
12
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| SMILES |
CC(C)C[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CN=CN1)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N2CCC[C@H]2C(=O)N[C@@H](CCSC)C(=O)N3CCC[C@H]3C(=O)N[C@@H](CC4=CC=CC=C4)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H]5CCCN5C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H]6CCC(=O)N6
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| InChi Key |
GGMAXEWLXWJGSF-PEWBXTNBSA-N
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| InChi Code |
InChI=1S/C69H108N22O16S/c1-39(2)32-47(85-57(96)43(17-9-26-76-68(71)72)82-63(102)52-20-12-29-90(52)65(104)45(18-10-27-77-69(73)74)83-58(97)44-22-23-54(93)80-44)59(98)88-50(37-92)61(100)86-48(34-41-35-75-38-79-41)60(99)81-42(16-7-8-25-70)56(95)78-36-55(94)89-28-11-19-51(89)62(101)84-46(24-31-108-3)66(105)91-30-13-21-53(91)64(103)87-49(67(106)107)33-40-14-5-4-6-15-40/h4-6,14-15,35,38-39,42-53,92H,7-13,16-34,36-37,70H2,1-3H3,(H,75,79)(H,78,95)(H,80,93)(H,81,99)(H,82,102)(H,83,97)(H,84,101)(H,85,96)(H,86,100)(H,87,103)(H,88,98)(H,106,107)(H4,71,72,76)(H4,73,74,77)/t42-,43-,44-,45-,46-,47-,48-,49-,50-,51-,52-,53-/m0/s1
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| Chemical Name |
(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-1-[2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-(diaminomethylideneamino)-2-[[(2S)-1-[(2S)-5-(diaminomethylideneamino)-2-[[(2S)-5-oxopyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxypropanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]hexanoyl]amino]acetyl]pyrrolidine-2-carbonyl]amino]-4-methylsulfanylbutanoyl]pyrrolidine-2-carbonyl]amino]-3-phenylpropanoic 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) |
H2O : ~100 mg/mL (~65.20 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 100 mg/mL (65.20 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 | 0.6520 mL | 3.2599 mL | 6.5198 mL | |
| 5 mM | 0.1304 mL | 0.6520 mL | 1.3040 mL | |
| 10 mM | 0.0652 mL | 0.3260 mL | 0.6520 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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