ML-290 (Synonyms: RXFP1 Agonist 8) |
رقم الكتالوجGC18594
One-Click Copy Product Info
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ML-290 هو الأول من نوعه في فئته وقوي مستقبلات الببتيد العائلي ريلاكسين / الأنسولين (RXFP1) ومنشط للجينات المضادة للليف ، مع EC50 من 94 نانومتر
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1482500-76-4
Sample solution is provided at 25 µL, 10mM.
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ML-290 is the first potent, selective, and metabolically stable small-molecule biased allosteric agonist of the relaxin receptor RXFP1, with an EC50 value of 94nM[1,2]. ML-290 is metabolically stable and commonly used in research on fibrosis and inflammation-related diseases, such as chronic kidney disease and liver fibrosis[2,3].
In vitro, treatment of human cardiac fibroblasts (HCF) with ML-290 (1μM) for 72h promoted MMP-2 expression and inhibited TGF-β1-induced phosphorylation of Smad2 and Smad3[1]. In human hepatic stellate cells (HSCs), ML-290 (5μM) treatment for 72h reduced COL1A1 gene expression while increasing the expression of MMP1 and PPARGC1A[4]. In LX-2 cells, a 24h treatment with ML-290 (100μM) downregulated RXFP1 mRNA expression by 9.8 ± 6.4-fold[5]. In HEK293T cells transiently transfected with two rabbit RXFP1 receptor variants (R1-RXFP1 and R2-RXFP2), ML-290 (5μM) treatment for 60min effectively stimulated cAMP production, though with lower potency compared to its effect on human RXFP1[6].
In vivo, a single intraperitoneal injection of ML-290 (37mg/kg) concurrently with CCl4 in humanized hRXFP1/hRXFP1 mice significantly suppressed the upregulation of pro-fibrotic genes (Acta2, Col1a1, and Tgfb1) in the liver at 20h post-treatment[4]. Intravenous administration of ML-290 (100μg/25 g body weight) in humanized hRXFP1/hRXFP1 female mice significantly increased heart rate within 26-40min after injection[7]. In a unilateral ureteral obstruction (UUO) model, intraperitoneal injection of ML-290 (30mg/kg; once daily) for 5 days in humanized hRXFP1/hRXFP1 mice significantly reduced renal apoptosis and inhibited Erk1/2 activity[8].
References:
[1] KOCAN M, SARWAR M, ANG S Y, et al. ML290 is a biased allosteric agonist at the relaxin receptor RXFP1[J]. Scientific Reports, 2017, 7: 2968.
[2] XIAO J, CHEN C Z, HUANG Z, et al. Discovery, optimization, and biological activity of the first potent and selective small-molecule agonist series of human relaxin receptor 1 (RXFP1)[EB/OL]. Probe Reports from the NIH Molecular Libraries Program, 2013-05-08.
[3] NG H H, MEDINA D, AGOULNIK A I, et al. A Novel Human Relaxin Receptor Agonist, ML290, Attenuates Atherosclerosis-and Chronic Kidney Disease-Induced Vascular Calcification in Mice[J]. Circulation, 2020, 142(Suppl_3): A17021-A17021.
[4] KAFTANOVSKAYA E M, NG H H, SOULA M, et al. Therapeutic effects of a small molecule agonist of the relaxin receptor ML290 in liver fibrosis[J]. The FASEB Journal, 2019, 33(11): 12435.
[5] MCBRIDE A, HOY A M, BAMFORD M J, et al. In search of a small molecule agonist of the relaxin receptor RXFP1 for the treatment of liver fibrosis[J]. Scientific Reports, 2017, 7: 10806.
[6] HUANG Z, MYHR C, BATHGATE R A D, et al. Activation of relaxin family receptor 1 from different mammalian species by relaxin peptide and small-molecule agonist ML290[J]. Frontiers in Endocrinology, 2015, 6: 128.
[7] KAFTANOVSKAYA E M, SOULA M, MYHR C, et al. Human relaxin receptor is fully functional in humanized mice and is activated by small molecule agonist ML290[J]. Journal of the Endocrine Society, 2017, 1(6): 712-725.
[8] NG H H, SOULA M, RIVAS B, et al. Anti-apoptotic and matrix remodeling actions of a small molecule agonist of the human relaxin receptor, ML290 in mice with unilateral ureteral obstruction[J]. Frontiers in Physiology, 2021, 12: 650769.
| Cell experiment [1]: | |
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Cell lines |
HCFs (fibrosis in human cardiac fibroblasts) |
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Preparation Method |
HCFs were treated with ML-290 (1μM) for 72h and analysed for MMP-2 expression. The optical density (OD) of MMP-2 was measured using a GS710 Calibrated Imaging Densitomer. HCFs were plated into 24-well plates (0.7 × 105 cells/well) and grown overnight to achieve a confluent monolayer. Cells were treated with ML-290 (1μM) in combination with TGF-β1 (2ng/ml final concentration) for 72h. Cells were serum-starved in M199 medium for 24h prior sample collection. Levels of p-Smad2 and p-Smad3 were detected using Sure-fire kits. |
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Reaction Conditions |
1μM; 72h |
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Applications |
ML-290 (1μM) increased MMP-2 expression in HCFs by 40%. Cells treated with TGF-β1 (2ng/ml) showed a 2.21 ± 0.17-fold increase in p-Smad2 and 1.41 ± 0.07-fold increase in p-Smad3. 1μM ML-290 (p-Smad2: 1.58 ± 0.34-fold/basal, p < 0.05; p-Smad3: 1.15 ± 0.05-fold/basal, p < 0.01) significantly inhibited the TGF-β1-induced increase in p-Smad2 and p-Smad3 in HCFs. |
| Animal experiment [2]: | |
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Animal models |
C57BL/6 (humanized hRXFP1/hRXFP1 female mice) |
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Preparation Method |
Heart rate (HR) was measured by tail cuff using a Non-Invasive Blood Pressure System. Basal measurements were recorded each minute for the first 10min. ML-290 (100μg/25g body weight) was administered via intravenous injection in the tail vein after which HR was recorded for 40min. |
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Dosage form |
100μg/25g body weight; i.v. |
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Applications |
IV injection of ML-290 (100μg/25g body weight) increased HR in unconscious hRXFP1 females but not wild-type (Wt) females. |
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References: |
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| Cas No. | 1482500-76-4 | SDF | |
| المرادفات | RXFP1 Agonist 8 | ||
| Chemical Name | 2-[[2-(1-methylethoxy)benzoyl]amino]-N-[3-[(trifluoromethyl)sulfonyl]phenyl]-benzamide | ||
| Canonical SMILES | O=S(C1=CC=CC(NC(C2=CC=CC=C2NC(C3=C(OC(C)C)C=CC=C3)=O)=O)=C1)(C(F)(F)F)=O | ||
| Formula | C24H21F3N2O5S | M.Wt | 506.5 |
| الذوبان | 0.14mg/mL in ethanol, 25mg/mL in DMSO, 30mg/mL in DMF | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.9743 mL | 9.8717 mL | 19.7433 mL |
| 5 mM | 394.9 μL | 1.9743 mL | 3.9487 mL |
| 10 mM | 197.4 μL | 987.2 μL | 1.9743 mL |
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Quality Control & SDS
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- Purity: >98.00% Appearance: A solid
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Average Rating: 5 (Based on Reviews and 33 reference(s) in Google Scholar.)