{{cs1 config|name-list-style=vanc|display-authors=6}} {{Drugbox | IUPAC_name = 4-oxo-6-((pyrimidin-2-ylthio)methyl)-4H-pyran-3-yl 4-nitrobenzoate | image = ML221_structure.png | image_class = skin-invert-image | width = 240
<!--Clinical data--> | tradename = | pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> | pregnancy_US = <!-- A / B / C / D / X --> | pregnancy_category = | legal_AU = <!-- S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 --> | legal_CA = | legal_UK = | legal_US = <!-- Schedule I / Schedule II / Schedule III --> | legal_status = | routes_of_administration =
<!--Pharmacokinetic data--> | bioavailability = | protein_bound = | excretion =
<!--Identifiers--> | CAS_number = 877636-42-5 | UNII = | PubChem = 7217941 | IUPHAR_ligand = | DrugBank = | ChemSpiderID = | ChEBI = | ChEMBL = | StdInChI = 1S/C17H11N3O6S/c21-14-8-13(10-27-17-18-6-1-7-19-17)25-9-15(14)26-16(22)11-2-4-12(5-3-11)20(23)24/h1-9H,10H2 | StdInChIKey = UASIRTUMPRQVFY-UHFFFAOYSA-N <!--Chemical data--> | C=17 | H=11 | N=3 | O=6 | S=1 | smiles = C1=CN=C(N=C1)SCC2=CC(=O)C(=CO2)OC(=O)C3=CC=C(C=C3)[N+](=O)[O-] }}
'''ML221''' is a drug which is a selective, small-molecule antagonist for the apelin receptor. It is primarily used for research into the function of this receptor pathway, but also has potential medical applications.<ref>{{cite journal | vauthors = Maloney PR, Khan P, Hedrick M, Gosalia P, Milewski M, Li L, Roth GP, Sergienko E, Suyama E, Sugarman E, Nguyen K, Mehta A, Vasile S, Su Y, Stonich D, Nguyen H, Zeng FY, Novo AM, Vicchiarelli M, Diwan J, Chung TD, Smith LH, Pinkerton AB | title = Discovery of 4-oxo-6-((pyrimidin-2-ylthio)methyl)-4H-pyran-3-yl 4-nitrobenzoate (ML221) as a functional antagonist of the apelin (APJ) receptor | journal = Bioorganic & Medicinal Chemistry Letters | volume = 22 | issue = 21 | pages = 6656–6660 | date = November 2012 | pmid = 23010269 | doi = 10.1016/j.bmcl.2012.08.105 | pmc = 3729231 }}</ref><ref>{{cite journal | vauthors = Hall C, Ehrlich L, Venter J, O'Brien A, White T, Zhou T, Dang T, Meng F, Invernizzi P, Bernuzzi F, Alpini G, Lairmore TC, Glaser S | title = Inhibition of the apelin/apelin receptor axis decreases cholangiocarcinoma growth | journal = Cancer Letters | volume = 386 | pages = 179–188 | date = February 2017 | pmid = 27894959 | doi = 10.1016/j.canlet.2016.11.025 | pmc = 5510601 }}</ref><ref>{{cite journal | vauthors = Rak A, Drwal E, Rame C, Knapczyk-Stwora K, Słomczyńska M, Dupont J, Gregoraszczuk EL | title = Expression of apelin and apelin receptor (APJ) in porcine ovarian follicles and in vitro effect of apelin on steroidogenesis and proliferation through APJ activation and different signaling pathways | journal = Theriogenology | volume = 96 | pages = 126–135 | date = July 2017 | pmid = 28532828 | doi = 10.1016/j.theriogenology.2017.04.014 | url = http://ruj.uj.edu.pl/xmlui/handle/item/41342 }}</ref><ref>{{cite journal | vauthors = Ishimaru Y, Shibagaki F, Yamamuro A, Yoshioka Y, Maeda S | title = An apelin receptor antagonist prevents pathological retinal angiogenesis with ischemic retinopathy in mice | journal = Scientific Reports | volume = 7 | issue = 1 | article-number = 15062 | date = November 2017 | pmid = 29118394 | doi = 10.1038/s41598-017-15602-3 | pmc = 5678128 | bibcode = 2017NatSR...715062I }}</ref><ref>{{cite journal | vauthors = Neelakantan D, Dogra S, Devapatla B, Jaiprasart P, Mukashyaka MC, Janknecht R, Dwivedi SK, Bhattacharya R, Husain S, Ding K, Woo S | title = Multifunctional APJ Pathway Promotes Ovarian Cancer Progression and Metastasis | journal = Molecular Cancer Research | volume = 17 | issue = 6 | pages = 1378–1390 | date = June 2019 | pmid = 30858172 | doi = 10.1158/1541-7786.MCR-18-0989 | pmc = 6548659 }}</ref><ref>{{cite journal | vauthors = Song K, Yang X, An G, Xia X, Zhao J, Xu X, Wan C, Liu T, Zheng Y, Ren S, Wang M, Chang G, Cronin SJ, Penninger JM, Jing T, Ou X, Rao S, Liu Z, Zhao XY | title = Targeting APLN/APJ restores blood-testis barrier and improves spermatogenesis in murine and human diabetic models | journal = Nature Communications | volume = 13 | issue = 1 | article-number = 7335 | date = November 2022 | pmid = 36443325 | doi = 10.1038/s41467-022-34990-3 | pmc = 9705293 | bibcode = 2022NatCo..13.7335S }}</ref><ref>{{cite journal | vauthors = Das M, Gurusubramanian G, Roy VK | title = Apelin receptor antagonist (ML221) treatment has a stimulatory effect on the testicular proliferation, antioxidants system and steroidogenesis in adult mice | journal = Neuropeptides | volume = 101 | article-number = 102354 | date = October 2023 | pmid = 37379791 | doi = 10.1016/j.npep.2023.102354 }}</ref><ref>{{cite journal | vauthors = Wang Q, Wang B, Zhang W, Zhang T, Liu Q, Jiao X, Ye J, Hao Y, Gao Q, Ma G, Hao C, Cui B | title = APLN promotes the proliferation, migration, and glycolysis of cervical cancer through the PI3K/AKT/mTOR pathway | journal = Archives of Biochemistry and Biophysics | volume = 755 | article-number = 109983 | date = May 2024 | pmid = 38561035 | doi = 10.1016/j.abb.2024.109983 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Bist G, Elsheikh A, Kim S, Huang RY, Ruszaj D, Woo S, You Y | title = Novel small molecule analogs for advancing apelin receptor antagonism with enhanced plasma and microsomal stability | journal = Bioorganic & Medicinal Chemistry Letters | volume = 129 | article-number = 130367 | date = December 2025 | pmid = 40784515 | doi = 10.1016/j.bmcl.2025.130367 }}</ref>
== References == {{reflist}}
Category:Esters Category:Nitrobenzene derivatives Category:Pyrans Category:Pyrimidines Category:Thioethers
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