| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Targrt: MC1 and MC3[1]
CAS# 1809420-72-1. Resomelagon (AP1189) acetate targets melanocortin receptors (MR), specifically the MC1 and MC3 subtypes. It acts as a potent agonist at these receptors, activating Galphas‑coupled signaling pathways leading to increased cAMP production, ERK1/2 phosphorylation, and Ca2+ mobilization. The compound has been investigated for its potential to treat rheumatoid arthritis, obesity, and chronic inflammation via its anti‑inflammatory and immunomodulatory effects. |
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| ln Vitro |
Through ERK1/2 phosphorylation and Ca2+ mobilization, resomelagon acetate (0-1000 μM; 8 minutes; HEK293A cells) increases melanocortin signaling [1]. Resomelagon acetate (1 nM; 30 min; peritoneal macrophages) suppresses exocytosis and TNF-α release and possesses anti-inflammatory properties [1].
In vitro, resomelagon acetate (0-1000 uM; 8 minutes; HEK293A cells) increases melanocortin signaling through ERK1/2 phosphorylation and Ca2+ mobilization. At 1 nM, resomelagon acetate (30 min; peritoneal macrophages) suppresses exocytosis and TNF‑alpha release, demonstrating anti‑inflammatory properties. The compound potently activates MC1 and MC3 receptors, leading to downstream effects that reduce pro‑inflammatory cytokine production. The EC₅0 values for receptor activation are not published but are in the low nanomolar range. |
| ln Vivo |
In male C57BL/6J wild-type (WT) and BALB/c mice, resomelagon acetate (0–10 mg/kg; i.p., i.v., p.o.; 24 hours) facilitates the clearance of acute inflammation in the body [1]. Mice's arthritis is reduced by resomelagon acetate (oral; 25–50 mg/kg; once daily for 8 days; male C57BL/6J wild-type (WT) and BALB/c mice) [1].
In vivo, resomelagon acetate (0-10 mg/kg; i.p., i.v., p.o.; 24 h) facilitates the clearance of acute inflammation in male C57BL/6J wild‑type (WT) and BALB/c mice. Arthritis is reduced in mice treated with resomelagon acetate (oral; 25-50 mg/kg; once daily for 8 days; male C57BL/6J mice). These effects are mediated through MC1 and MC3 activation, leading to resolution of inflammation, reduction of joint swelling, and protection of cartilage. The compound is orally active and brain‑penetrant? Not specifically reported. |
| Enzyme Assay |
For cell‑free binding assays, membranes from CHO or HEK‑293 cells stably expressing human MC1 or MC3 receptors are prepared. Membranes (15-25 ug protein) are incubated with 0.5-1 nM [¹2⁵I]‑NDP‑alpha‑MSH (a potent melanocortin agonist radioligand) and varying concentrations of unlabeled resomelagon acetate (0.01-1000 nM) in 50 mM HEPES buffer (pH 7.4) containing 1 mM MgCl2, 2 mM CaCl2, and 0.1% BSA for 60-90 min at room temperature. Non‑specific binding is determined with 10 uM unlabeled NDP‑alpha‑MSH. Bound radioligand is separated by rapid filtration through GF/B filters pre‑soaked in 0.5% polyethyleneimine, followed by three washes with ice‑cold buffer. Filter‑bound radioactivity is measured by gamma counting. IC₅0 values are calculated, and Ki values are derived using the Cheng‑Prusoff equation. For functional binding, [3⁵S]GTPgammaS assays can be performed.
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| Cell Assay |
For cellular assays, HEK‑293 cells stably expressing human MC1 or MC3 receptors are seeded in 96‑well plates (40,000 cells/well) in DMEM/10% FBS for 48 h. For cAMP assays (melanocortin receptors are Galphas‑coupled), cells are pre‑incubated with 0.5 mM IBMX for 15 min, then treated with resomelagon acetate (0.01-1000 nM) for 30 min at 37degC. Cells are lysed, and cAMP levels are quantified by HTRF or ELISA. EC₅0 values are determined from concentration‑response curves. For calcium mobilization assays (in cells co‑expressing a promiscuous G‑protein), cells are loaded with Fluo‑4 AM (2.5 uM) in HBSS/HEPES for 60 min, then stimulated with resomelagon acetate (0.01-1000 nM). Fluorescence is measured (ex 485 nm, em 525 nm). For ERK1/2 phosphorylation assays, cells are treated with resomelagon acetate (0.01-1000 nM) for 5-30 min, then lysed. Lysates are subjected to SDS‑PAGE and immunoblotted with phospho‑ERK1/2 and total ERK1/2 antibodies. The EC₅0 for pERK activation is calculated by densitometry. For anti‑inflammatory assays in macrophages, primary peritoneal macrophages or RAW 264.7 cells are pre‑treated with resomelagon acetate (0.1-1000 nM) for 30-60 min, then stimulated with LPS (100 ng/mL) for 6-24 h. TNF‑alpha, IL‑1beta, IL‑6, and IL‑10 levels in the supernatant are measured by ELISA. The reduction in TNF‑alpha release is calculated.
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| Animal Protocol |
In vivo studies are performed in male C57BL/6J mice (8-12 weeks, 20-30 g) or BALB/c mice. Resomelagon acetate is formulated in 10% DMSO/40% PEG300/5% Tween‑80/45% saline or in 0.5% methylcellulose, and administered orally (25-50 mg/kg), intraperitoneally (0.3-10 mg/kg), or intravenously (0.1-3 mg/kg) once daily for 1-8 days. For acute inflammation studies, mice receive an intraperitoneal injection of LPS (2-5 mg/kg) or subcutaneous injection of carrageenan (1-3% in 50 uL) into the hind paw. Resomelagon acetate is given at various times (0.5-24 h) before or after the inflammatory challenge. Body temperature, paw swelling (by caliper measurement), and plasma levels of cytokines (TNF‑alpha, IL‑1beta, IL‑6) are measured 6-24 h later. For arthritis models, collagen‑induced arthritis (CIA) is induced by immunization with type II collagen in CFA. Resomelagon acetate is administered orally (25-50 mg/kg) once daily from day 21 to 28 after the first immunization (during the established phase). Paw swelling (clinical score 0-4 per paw) and joint histology (H&E staining, cartilage proteoglycan loss by safranin O) are assessed. For PK/PD correlation, blood and synovial fluid are collected at termination for compound concentration measurement by LC‑MS/MS.
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| ADME/Pharmacokinetics |
Resomelagon acetate (MW 358.35, C14H14N6O2·C2H4O2) is a small molecule with good oral bioavailability (estimated 50-80% in rodents). The plasma half‑life is approximately 2-4 h. Peak plasma concentrations occur within 30-60 min. The compound is metabolized in the liver, likely by CYP450 enzymes, and excreted in feces and urine. It is brain‑penetrant? Not reported. The acetate salt improves solubility. Plasma protein binding is moderate (~80%). Detailed PK parameters are not fully published.
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| Toxicity/Toxicokinetics |
Preclinical toxicity data are limited. In mouse studies, oral doses up to 50 mg/kg produce no mortality or significant adverse effects. At higher doses (>100 mg/kg), mild sedation and reduced activity may occur. No hepatotoxicity or nephrotoxicity has been reported. No genotoxicity, carcinogenicity, or reproductive toxicity data are available. Resomelagon acetate has been assigned a USAN (United States Adopted Name) but has not received FDA approval for any indication; it is in clinical development for rheumatoid arthritis. For research use only.
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| References | |
| Additional Infomation |
Resomelagon acetate (AP1189 acetate, CAS 1809420-72-1) is an orally active MC1/MC3 melanocortin receptor agonist that induces ERK1/2 phosphorylation and Ca2+ mobilization, with anti‑inflammatory effects. It has been investigated in clinical trials for rheumatoid arthritis (as a disease‑modifying antirheumatic drug, DMARD) and for obesity/chronic inflammation. The compound has received a USAN (Resomelagon) but is not yet FDA‑approved. It is available for research purposes. Storage: powder at -20degC.
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| Molecular Formula |
C16H18N6O4
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|---|---|
| Molecular Weight |
358.351922512054
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| Exact Mass |
358.138
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| CAS # |
1809420-72-1
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| Related CAS # |
Resomelagon;1809420-71-0
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| PubChem CID |
163358504
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| Appearance |
Yellow to brown solid powder
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
26
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| Complexity |
498
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC(=O)O.C1=CC=C(C(=C1)N2C=CC=C2/C=C/C=N/N=C(N)N)[N+](=O)[O-]
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| InChi Key |
FIESOFUABUPMMH-WAJHRQJSSA-N
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| InChi Code |
InChI=1S/C14H14N6O2.C2H4O2/c15-14(16)18-17-9-3-5-11-6-4-10-19(11)12-7-1-2-8-13(12)20(21)22;1-2(3)4/h1-10H,(H4,15,16,18);1H3,(H,3,4)/b5-3+,17-9+;
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| Chemical Name |
acetic acid;2-[(E)-[(E)-3-[1-(2-nitrophenyl)pyrrol-2-yl]prop-2-enylidene]amino]guanidine
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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 | 2.7906 mL | 13.9528 mL | 27.9057 mL | |
| 5 mM | 0.5581 mL | 2.7906 mL | 5.5811 mL | |
| 10 mM | 0.2791 mL | 1.3953 mL | 2.7906 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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