AGN 195183 (Synonyms: IRX-5183; VTP-195183; NRX-195183) |
Catalog No.GC35265
One-Click Copy Product Info
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AGN 195183 is an orally active, selective agonist for the retinoic acid receptor α (RARα).
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 367273-07-2
Sample solution is provided at 25 µL, 10mM.
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AGN 195183 is an orally active, selective agonist for the retinoic acid receptor α (RARα)[1-2]. AGN 195183 has high affinity for RARα (Kd=3nM) and is inactive against RARβ/γ. AGN 195183 is used in research related to acute myeloid leukemia, multiple myeloma, and breast cancer[3].
In vitro, AGN 195183 (0-1μM) was used to treat the ER-positive human breast cancer cell line T-47D and the ER-negative human breast cancer cell line SK-BR-3 for 1-8 days. AGN 195183 significantly inhibited cell growth[4]. Treatment of the human promyelocytic leukemia cell line NB-4 with AGN 195183 (100nM) for 96 hours effectively induced neutrophil differentiation; co-treatment of NB-4 cells with AGN 195183 (100nM) and 10nM 1,25-dihydroxyvitamin D3 for 96 hours effectively induced monocyte differentiation[5].
In vivo, AGN 195183 (4mg/kg/day and 20mg/kg/day) was administered orally to treat Wistar rats with glomerulonephritis (Thy-GN), starting from day 23 after model induction and continuing for 67 days. AGN 195183 significantly reduced protein excretion and blood pressure, improved histological indices such as the glomerulosclerosis index, glomerular and interstitial cell counts, and interstitial area, and reduced glomerular macrophage infiltration and the gene expression of TGF-β1 and Prepro-ET-1[6]. AGN 195183 (4, 12, 36mg/kg/day; for 20 days) was administered daily by gavage to 2-month-old female CD-1 mice subcutaneously implanted with a Matrigel/rhBMP-2 mixture. AGN 195183 significantly inhibited the formation of ectopic bone-like tissue, reduced mineralized tissue volume, cartilage and bone content, the number of TRAP-positive osteoclasts and vascularization, and downregulated the expression of key chondrogenic and osteogenic genes such as Sox9, Runx2, and VEGFα[7].
References:
[1] Wang Q, Lee D, Sysounthone V, et al. 1,25-dihydroxyvitamin D3 and retonic acid analogues induce differentiation in breast cancer cells with function- and cell-specific additive effects. Breast Cancer Res Treat. 2001 May;67(2):157-68.
[2] Chee LC, Hendy J, Purton LE, et al. ATRA and the specific RARα agonist, NRX195183, have opposing effects on the clonogenicity of pre-leukemic murine AML1-ETO bone marrow cells. Leukemia. 2013 Jun;27(6):1369-80.
[3] Herbert KE, Walkley CR, Winkler IG, et al. Granulocyte colony-stimulating factor and an RARalpha specific agonist, VTP195183, synergize to enhance the mobilization of hematopoietic progenitor cells. Transplantation. 2007 Feb 27;83(4):375-84.
[4] Beard RL, Duong TT, Teng M, et al. Synthesis and biological activity of retinoic acid receptor-alpha specific amides. Bioorg Med Chem Lett. 2002 Nov 4;12(21):3145-8.
[5] Brown G, Marchwicka A, Cunningham A, et al. Antagonizing Retinoic Acid Receptors Increases Myeloid Cell Production by Cultured Human Hematopoietic Stem Cells. Arch Immunol Ther Exp (Warsz). 2017 Feb;65(1):69-81.
[6] Schaier M, Liebler S, Schade K, et al. Retinoic acid receptor alpha and retinoid X receptor specific agonists reduce renal injury in established chronic glomerulonephritis of the rat. J Mol Med (Berl). 2004 Feb;82(2):116-25.
[7] Shimono K, Morrison TN, Tung WE, et al. Inhibition of ectopic bone formation by a selective retinoic acid receptor alpha-agonist: a new therapy for heterotopic ossification? J Orthop Res. 2010 Feb;28(2):271-7.
| Cell experiment [1]: | |
Cell lines | T-47D cells (human breast cancer cell line, estrogen receptor positive) and SK-BR-3 cells (human breast cancer cell line, estrogen receptor negative) |
Preparation Method | The cell lines were maintained in Dulbecco's minimal essential medium (DMEM) supplemented with 10% fetal bovine serum (FBS). Cells were treated with the AGN 195183 (0-1μM) for 1-8 days. |
Reaction Conditions | 0-1μM; 1-8 days. |
Applications | AGN 195183 significantly inhibited the growth of T-47D cells by approximately 60% and inhibited the growth of SK-BR-3 cells by approximately 93%. |
| Animal experiment [2]: | |
Animal models | Male Wistar rats with established chronic anti-Thy1.1 glomerulonephritis (Thy-GN) |
Preparation Method | Chronic mesangioproliferative Thy-GN was induced in rats by intravenous injection of monoclonal antibody (MoAb) 1-22-3. Oral treatment with AGN 195183 (4 or 20mg/kg/day) began on day 23 after disease induction and continued for 45 days. |
Dosage form | 4 or 20mg/kg/day; p.o.; daily administration for 45 days. |
Applications | AGN 195183 significantly reduced albuminuria and normalized elevated blood pressure in nephritic rats. AGN 195183 also significantly improved renal histology, as indicated by a lower glomerulosclerosis index, reduced glomerular and interstitial cell counts, and a smaller interstitial area. AGN 195183 treatment decreased glomerular macrophage infiltration and attenuated the increased glomerular gene expression of TGF-β1 and prepro-ET-1. |
References: | |
| Cas No. | 367273-07-2 | SDF | |
| Synonyms | IRX-5183; VTP-195183; NRX-195183 | ||
| Canonical SMILES | O=C(O)C1=C(F)C=C(NC(C2=C(O)C(Cl)=C3C(C)(C)CCC(C)(C)C3=C2)=O)C=C1F | ||
| Formula | C22H22ClF2NO4 | M.Wt | 437.86 |
| Solubility | DMSO: ≥ 62 mg/mL (141.60 mM) | 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 | 2.2838 mL | 11.4192 mL | 22.8384 mL |
| 5 mM | 456.8 μL | 2.2838 mL | 4.5677 mL |
| 10 mM | 228.4 μL | 1.1419 mL | 2.2838 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
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Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >99.50% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 22 reference(s) in Google Scholar.)