Home GPCR & G Protein Angiotensin Receptor antagonist ML221 For research use only.

ML221

ML221 is a potent apelin receptor (APJ) functional antagonist in cell-based assays that is >37-fold selective over the closely related angiotensin II type 1 (AT1) receptor. The IC50 values of ML221 are 0.70 and 1.75 μM in a cAMP assay and β-arrestin assay, respectively.

ML221 Chemical Structure

ML221 Chemical Structure

CAS No. 877636-42-5

Purity & Quality Control

Batch: S869501 DMSO]9 mg/mL]false]Water]Insoluble]false]Ethanol]Insoluble]false Purity: 99.76%
99.76

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Biological Activity

Description ML221 is a potent apelin receptor (APJ) functional antagonist in cell-based assays that is >37-fold selective over the closely related angiotensin II type 1 (AT1) receptor. The IC50 values of ML221 are 0.70 and 1.75 μM in a cAMP assay and β-arrestin assay, respectively.
Targets
apelin receptor [1]
(β-arrestin assay)
1.75 μM
In vitro
In vitro In a PAMPA permeability assay, ML221 exhibits moderate permeability. ML221 displays moderate plasma and poor microsomal stability, as it is rapidly metabolized in both human and mouse liver homogenates (4.2% and 4.9% remaining at 60 min). It shows no toxicity (>50 μM) toward human hepatocytes. ML221 displays limited cross reactivity against a range of GPCRs[1]. ML221 inhibits endothelial cell proliferation by blocking apelin-APJ signaling without affecting the expression of VEGF and VEGFR2[2].
Cell Research Cell lines bEnd.3 cells
Concentrations 0–30 μM
Incubation Time 24 h
Method

The proliferation of bEnd.3 cells following 24 h incubation with ML221 (0-30 μM) are assessed by the MTT assay and the BrdU incorporation assay. Mouse endothelial cell line bEnd.3 cells are maintained in Dulbecco's modified Eagle's medium supplemented with 10% heat-inactivated fetal bovine serum. The cells are plated at a density of 2.5 × 104/well in 24 well culture plates for the MTT assay and the BrdU incorporation assay. To perform the BrdU incorporation assay, 10 μM BrdU is added to the culture medium. After 2 h, the cells are fixed with 4% paraformaldehyde for 10 minutes. After removing the 4% paraformaldehyde, the cells are incubated with 2 M hydrochloric acid for 10 min at 37℃ for DNA hydrolysis, followed by neutralization with 0.1 M Sodium Borate buffer (pH 8.5) for 30 min at room temperature. Intranuclear BrdU is labeled with mouse anti-BrdU antibodies. The primary antibody is visualized with biotinylated goat anti-mouse IgG antibodies plus streptavidin fluorescein isothiocyanate. Nuclei are detected with Hoechst33342. The BrdU incorporation rate is determined by calculating the numbers of BrdU positive cells per Hoechst positive cells.
In Vivo
In vivo Intraperitoneal administration of ML221 inhibits pathological angiogenesis but enhances the recovery of normal vessels into the ischemic regions in the retina of the OIR model mice[2]. A single application of ML221 alleviates mechanical allodynia and heat hyperalgesia 7 days following chronic constriction injury (CCI), in a dose‑dependent manner. Intraspinal delivery of ML221, at the onset of and in fully‑established neuropathic pain, persistently attenuates CCI‑induced pain hypersensitivity, indicating that the apelin‑APJ system is involved in initiating and maintaining pain. Intrathecal ML221 downregulates phosphorylated extracellular signal‑related kinase (ERK) in the rat spinal cord dorsal horn, suggesting that the effect of apelin on neuropathic pain may be mediated via ERK signaling[3].
Animal Research Animal Models An ischemic retinopathy mouse model (C57BL/6 N mice)
Dosages 10 mg/kg
Administration i.p.

Chemical Information & Solubility

Molecular Weight 385.35 Formula

C17H11N3O6S
CAS No. 877636-42-5 SDF --
Smiles C1=CN=C(N=C1)SCC2=CC(=O)C(=CO2)OC(=O)C3=CC=C(C=C3)[N+](=O)[O-]
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 9 mg/mL ( (23.35 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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