WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H532242
CAS#: 877636-42-5
Description: ML221 is an antagonist of the apelin (APJ) receptor.
Hodoodo Cat#: H532242
Name: ML221
CAS#: 877636-42-5
Chemical Formula: C17H11N3O6S
Exact Mass: 385.04
Molecular Weight: 385.350
Elemental Analysis: C, 52.99; H, 2.88; N, 10.90; O, 24.91; S, 8.32
Synonym: ML221; ML 221; ML-221.
IUPAC/Chemical Name: [4-oxo-6-(pyrimidin-2-ylsulfanylmethyl)pyran-3-yl] 4-nitrobenzoate
InChi Key: UASIRTUMPRQVFY-UHFFFAOYSA-N
InChi Code: InChI=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
SMILES Code: O=C(OC1=COC(CSC2=NC=CC=N2)=CC1=O)C3=CC=C([N+]([O-])=O)C=C3
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info:
| Biological target: | ML221 is a potent apelin (APJ) functional antagonist, inhibiting apelin-13-mediated activation of APJ, with IC50s of 0.70 μM in the cAMP assay, and 1.75 μM in the β-arrestin assay, and EC80 of 10 nM in both assays. |
| In vitro activity: | ML221 significantly inhibited the proliferation of multiple HCC cell lines (HepG2, PLC5, HKCI-2 and HKCI-10) in a time- and dose- dependent manner (Figure 6A). As compared to normal liver cell LO2, HCC cells are more sensitive to ML221 treatment (Figure 6A). To assess the specific and cytotoxic effects of ML221 on HCC cells, this study further treated Miha, HepG2 and PLC5 with 50 μM ML221 for three different time intervals (day 0, 2 and 3). Consistently, ML221 at 50 μM was non-toxic against normal liver cell line Miha, but significantly suppressed the growth of HCC cell lines HepG2 and PLC5 (Figure S6A). ML221 also effectively inhibited colony formation of HKCI-2 and HKCI-10 cells in a dose-response manner, without affecting APLN expression (Figure 6B and S6B). Reference: Theranostics. 2019; 9(18): 5246–5260. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6691573/ |
| In vivo activity: | As presented above, increased expression of the spinal apelin-APJ system contributes to CCI-induced neuropathic pain. As ERK signaling is implicated in the effects of apelin, the present study investigated whether apelin-induced nociceptive behaviors were mediated via the ERK signaling pathway. Rats were assigned to sham, CCI, CCI + DMSO, and CCI + ML221 groups, respectively. A single intrathecal injection of ML221 (10 µg) or vehicle (DMSO) was performed 7 days post-surgery, and L4-L5 SC segments were harvested 2 h post-injection for the assessment of ERK and phosphorylated ERK levels. As presented in Fig. 6, phosphorylated ERK levels were increased in the CCI group compared with the sham group. Phosphorylated ERK induction was alleviated by a single intrathecal injection of ML221, corroborating the results obtained in the behavioral tests as described above. The present data indicated that the spinal apelin-APJ system may be involved in neuropathic pain via the ERK signaling pathway. Reference: Mol Med Rep. 2017 Aug; 16(2): 1223–1231. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5562064/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 11.2 | 29.09 | |
| DMF | 10.0 | 25.95 | |
| DMF:PBS (pH 7.2) (1:30) | 0.0 | 0.08 |
The following data is based on the product molecular weight 385.35 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Chen H, Wong CC, Liu D, Go MYY, Wu B, Peng S, Kuang M, Wong N, Yu J. APLN promotes hepatocellular carcinoma through activating PI3K/Akt pathway and is a druggable target. Theranostics. 2019 Jul 9;9(18):5246-5260. doi: 10.7150/thno.34713. PMID: 31410213; PMCID: PMC6691573. 2. Zhou L, Sun H, Cheng R, Fan X, Lai S, Deng C. ELABELA, as a potential diagnostic biomarker of preeclampsia, regulates abnormally shallow placentation via APJ. Am J Physiol Endocrinol Metab. 2019 May 1;316(5):E773-E781. doi: 10.1152/ajpendo.00383.2018. Epub 2019 Mar 12. PMID: 30860880. 3. Xiong Q, He W, Wang H, Zhou J, Zhang Y, He J, Yang C, Zhang B. Effect of the spinal apelin‑APJ system on the pathogenesis of chronic constriction injury‑induced neuropathic pain in rats. Mol Med Rep. 2017 Aug;16(2):1223-1231. doi: 10.3892/mmr.2017.6734. Epub 2017 Jun 9. PMID: 28627589; PMCID: PMC5562064. 4. 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. Inhibition of the apelin/apelin receptor axis decreases cholangiocarcinoma growth. Cancer Lett. 2017 Feb 1;386:179-188. doi: 10.1016/j.canlet.2016.11.025. Epub 2016 Nov 26. PMID: 27894959; PMCID: PMC5510601. |
| In vitro protocol: | 1. Chen H, Wong CC, Liu D, Go MYY, Wu B, Peng S, Kuang M, Wong N, Yu J. APLN promotes hepatocellular carcinoma through activating PI3K/Akt pathway and is a druggable target. Theranostics. 2019 Jul 9;9(18):5246-5260. doi: 10.7150/thno.34713. PMID: 31410213; PMCID: PMC6691573. 2. Zhou L, Sun H, Cheng R, Fan X, Lai S, Deng C. ELABELA, as a potential diagnostic biomarker of preeclampsia, regulates abnormally shallow placentation via APJ. Am J Physiol Endocrinol Metab. 2019 May 1;316(5):E773-E781. doi: 10.1152/ajpendo.00383.2018. Epub 2019 Mar 12. PMID: 30860880. |
| In vivo protocol: | 1. Xiong Q, He W, Wang H, Zhou J, Zhang Y, He J, Yang C, Zhang B. Effect of the spinal apelin‑APJ system on the pathogenesis of chronic constriction injury‑induced neuropathic pain in rats. Mol Med Rep. 2017 Aug;16(2):1223-1231. doi: 10.3892/mmr.2017.6734. Epub 2017 Jun 9. PMID: 28627589; PMCID: PMC5562064. 2. 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. Inhibition of the apelin/apelin receptor axis decreases cholangiocarcinoma growth. Cancer Lett. 2017 Feb 1;386:179-188. doi: 10.1016/j.canlet.2016.11.025. Epub 2016 Nov 26. PMID: 27894959; PMCID: PMC5510601. |
1: Roche J, Ramé C, Reverchon M, Mellouk N, Rak A, Froment P, Dupont J. Apelin (APLN) regulates progesterone secretion and oocyte maturation in bovine ovarian cells. Reproduction. 2017 Mar 1. pii: REP-16-0677. doi: 10.1530/REP-16-0677. [Epub ahead of print] PubMed PMID: 28250234.
2: 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. Inhibition of the apelin/apelin receptor axis decreases cholangiocarcinoma growth. Cancer Lett. 2017 Feb 1;386:179-188. doi: 10.1016/j.canlet.2016.11.025. PubMed PMID: 27894959.
3: Sakamoto K, Murakami Y, Sawada S, Ushikubo H, Mori A, Nakahara T, Ishii K. Apelin-36 is protective against N-methyl-D-aspartic-acid-induced retinal ganglion cell death in the mice. Eur J Pharmacol. 2016 Nov 15;791:213-220. doi: 10.1016/j.ejphar.2016.08.036. PubMed PMID: 27590359.
4: Roche J, Ramé C, Reverchon M, Mellouk N, Cornuau M, Guerif F, Froment P, Dupont J. Apelin (APLN) and Apelin Receptor (APLNR) in Human Ovary: Expression, Signaling, and Regulation of Steroidogenesis in Primary Human Luteinized Granulosa Cells. Biol Reprod. 2016 Nov;95(5):104. PubMed PMID: 27683264.
5: 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. 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. Bioorg Med Chem Lett. 2012 Nov 1;22(21):6656-60. doi: 10.1016/j.bmcl.2012.08.105. PubMed PMID: 23010269; PubMed Central PMCID: PMC3729231.
