| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Targets |
MM 07 targets the apelin receptor (APJ), a class A G protein-coupled receptor (GPCR). The compound exhibits biased agonism at this receptor, showing preferential activation of the G protein-mediated signaling pathway while displaying reduced beta-arrestin recruitment and receptor internalization compared to the native apelin-13 peptide. This biased signaling profile is considered advantageous for therapeutic applications as it may reduce desensitization and improve the pharmacokinetic profile.
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| ln Vitro |
MM 07 competes for the human apelin receptor in CHO-K1 cells (KD, 300 nM) and human heart (KD, 172 nM, n=3) combination with nanomolar affinity [Glp65, Nle75, Tyr77] [125I]apelin-13 [1].
In vitro, MM 07 stimulates endothelial nitric oxide synthase (eNOS) phosphorylation and expression in human pulmonary arterial endothelial cells. It promotes endothelial cell proliferation and attenuates apoptosis. The compound exhibits binding affinity with a KD of 300 nM in CHO-K1 cells and 172 nM in human heart tissue. MM 07 competes with nanomolar affinity for binding to [Glp65,Nle75,Tyr77][125I]apelin-13 at the apelin receptor. The compound shows comparable activity to native apelin in G-protein mediated pathways but lower beta-arrestin activity. |
| ln Vivo |
MM 07 decreased vascular resistance but increased cardiac output in a dose-dependent manner without changing blood pressure. Both the [Pyr1]apelin-13 and MM 07 treatment groups saw a considerable drop in blood pressure following SNAP administration; however, although the MM 07 group's SNAP reaction resulted in a significant increase in cardiac output, the [Pyr1]apelin-13 group's cardiac output was greatly reduced. The body temperature, heart rate, and respiration rate were not significantly altered by either peptide. Both MM 07 and [Pyr1]apelin 13 raise peak velocity above basal values [1].
In vivo, MM 07 demonstrates positive inotropic effects and vasodilatory activity. In a Sugen/hypoxia-induced model of pulmonary arterial hypertension, MM 07 treatment for 4 weeks significantly reversed detrimental structural and hemodynamic changes, showing efficacy at least comparable to the endothelin antagonist macitentan. MM 07 causes a rapid, dose-dependent increase in cardiac output and decreases vascular resistance without a corresponding effect on blood pressure. In human forearm studies, MM 07 induced rapid peripheral arterial dilatation with no evidence of desensitization upon repeated infusions. |
| Enzyme Assay |
Receptor binding assays are performed using membrane preparations from cells expressing human recombinant apelin receptors. Competition binding experiments are conducted with [Glp65,Nle75,Tyr77][125I]apelin-13 as the radioligand. Membranes are incubated with varying concentrations of MM 07 and a fixed concentration of radioligand in binding buffer at room temperature for a defined period. Nonspecific binding is determined in the presence of excess unlabeled apelin-13. Bound and free radioligands are separated by rapid filtration through glass fiber filters, and retained radioactivity is measured by scintillation counting to calculate KD and IC50 values.
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| Cell Assay |
Cellular assays are performed using CHO-K1 cells stably expressing the human apelin receptor. Cells are cultured in appropriate media and seeded into microplates prior to compound treatment. For beta-arrestin recruitment assays, cells expressing beta-arrestin biosensors are treated with MM 07 at various concentrations, and the signal is measured using a plate reader. For G protein activation, GTPgammaS binding assays are conducted on cell membranes. Endothelial cell assays use human pulmonary arterial endothelial cells treated with MM 07, followed by Western blot analysis for eNOS phosphorylation and expression, and viability assays for proliferation and apoptosis assessment.
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| Animal Protocol |
In vivo studies are conducted in rodent models of pulmonary arterial hypertension, such as the Sugen/hypoxia-induced PAH model. MM 07 is administered via appropriate routes (e.g., subcutaneous or intravenous injection) at defined doses and schedules over a treatment period of several weeks. Hemodynamic parameters including cardiac output, vascular resistance, and blood pressure are measured using invasive or non-invasive techniques. Cardiac structure and function are assessed by echocardiography. Tissue samples are collected post-mortem for histological analysis of vascular remodeling and molecular analysis of signaling pathways.
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| ADME/Pharmacokinetics |
Detailed pharmacokinetic data for MM 07 are limited in publicly available literature. As a cyclic peptide, MM 07 is expected to have moderate stability in circulation and may be subject to proteolytic degradation. Studies in human forearm demonstrated that repeated infusions of MM 07 did not produce desensitization, suggesting favorable pharmacokinetic behavior without rapid tachyphylaxis. Research supports the development of G protein-biased apelin receptor agonists with improved pharmacokinetic profiles for human therapeutic use.
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| Toxicity/Toxicokinetics |
Comprehensive toxicology data for MM 07 are not extensively documented in public sources. The compound is intended for research use only and not for human therapeutic application. In preclinical studies, MM 07 has been administered in animal models without reported adverse effects at the doses used for efficacy evaluation. As with all peptide-based research compounds, standard safety precautions should be observed during handling, including the use of appropriate personal protective equipment and adherence to institutional biosafety guidelines.
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| References | |
| Additional Infomation |
MM 07 is a cyclic peptide (CRPRLCHKGPMPF with disulfide bridge Cys1-Cys6) being developed as a biased apelin receptor agonist for cardiovascular indications. Its biased signaling profile (G protein pathway bias over beta-arrestin) is a key differentiator from native apelin and may offer therapeutic advantages including reduced desensitization. The compound has shown efficacy in reversing pulmonary arterial hypertension in preclinical models and is being investigated for its translational potential in human cardiovascular disease. MM 07 is for research purposes only and has not been approved for clinical use.
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| Molecular Formula |
C67H106N22O14S3
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|---|---|
| Molecular Weight |
1539.89254903793
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| Exact Mass |
1538.742
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| CAS # |
1876450-21-3
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| PubChem CID |
134828250
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| Appearance |
White to off-white solid powder
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| LogP |
-5.1
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| Hydrogen Bond Donor Count |
17
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| Hydrogen Bond Acceptor Count |
22
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| Rotatable Bond Count |
34
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| Heavy Atom Count |
106
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| Complexity |
3060
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| Defined Atom Stereocenter Count |
12
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| SMILES |
S(C)CC[C@@H](C(N1CCC[C@H]1C(N[C@H](C(=O)O)CC1C=CC=CC=1)=O)=O)NC([C@@H]1CCCN1C(CNC([C@H](CCCCN)NC([C@H](CC1=CN=CN1)NC([C@@H]1CSSC[C@@H](C(N[C@@H](CCC/N=C(\N)/N)C(N2CCC[C@H]2C(N[C@H](C(N[C@H](C(N1)=O)CC(C)C)=O)CCC/N=C(\N)/N)=O)=O)=O)N)=O)=O)=O)=O)=O
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| InChi Key |
RKFGCZWTURNFPN-SVENNQHVSA-N
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| InChi Code |
InChI=1S/C67H106N22O14S3/c1-38(2)30-46-57(94)86-49(36-106-105-35-41(69)54(91)81-44(18-10-25-76-67(72)73)63(100)88-27-12-20-51(88)61(98)80-43(56(93)83-46)17-9-24-75-66(70)71)59(96)84-47(32-40-33-74-37-78-40)58(95)79-42(16-7-8-23-68)55(92)77-34-53(90)87-26-11-19-50(87)60(97)82-45(22-29-104-3)64(101)89-28-13-21-52(89)62(99)85-48(65(102)103)31-39-14-5-4-6-15-39/h4-6,14-15,33,37-38,41-52H,7-13,16-32,34-36,68-69H2,1-3H3,(H,74,78)(H,77,92)(H,79,95)(H,80,98)(H,81,91)(H,82,97)(H,83,93)(H,84,96)(H,85,99)(H,86,94)(H,102,103)(H4,70,71,75)(H4,72,73,76)/t41-,42-,43-,44-,45-,46-,47-,48-,49-,50-,51-,52-/m0/s1
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| Chemical Name |
(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-1-[2-[[(2S)-6-amino-2-[[(2S)-2-[[(3S,6R,11R,14S,17S,20S)-6-amino-3,17-bis[3-(diaminomethylideneamino)propyl]-14-(2-methylpropyl)-2,5,13,16,19-pentaoxo-8,9-dithia-1,4,12,15,18-pentazabicyclo[18.3.0]tricosane-11-carbonyl]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) |
DMSO : ~62.5 mg/mL (~40.59 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 6.25 mg/mL (4.06 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 62.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 6.25 mg/mL (4.06 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 62.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. View More
Solubility in Formulation 3: ≥ 6.25 mg/mL (4.06 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.6494 mL | 3.2470 mL | 6.4940 mL | |
| 5 mM | 0.1299 mL | 0.6494 mL | 1.2988 mL | |
| 10 mM | 0.0649 mL | 0.3247 mL | 0.6494 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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