RG-7112

• CAT Number: I005585
• CAS Number: 939981-39-2
• Molecular Formula: C₃₈H₄₈Cl₂N₄O₄S
• Molecular Weight: 727.78
• Purity: ≥95%
• Target: MDM2
• Solubility: 10 mM in DMSO
• Storage: Store at -20°C
• IUPAC Name: [(4S,5R)-2-(4-tert-butyl-2-ethoxyphenyl)-4,5-bis(4-chlorophenyl)-4,5-dimethylimidazol-1-yl]-[4-(3-methylsulfonylpropyl)piperazin-1-yl]methanone
• InChI: InChI=1S/C38H48Cl2N4O4S/c1-8-48-33-26-29(36(2,3)4)14-19-32(33)34-41-37(5,27-10-15-30(39)16-11-27)38(6,28-12-17-31(40)18-13-28)44(34)35(45)43-23-21-42(22-24-43)20-9-25-49(7,46)47/h10-19,26H,8-9,20-25H2,1-7H3/t37-,38+/m0/s1
• InChIKey: QBGKPEROWUKSBK-QPPIDDCLSA-N
• SMILES: CCOC1=C(C=CC(=C1)C(C)(C)C)C2=NC(C(N2C(=O)N3CCN(CC3)CCCS(=O)(=O)C)(C)C4=CC=C(C=C4)Cl)(C)C5=CC=C(C=C5)Cl

RG7112（Cat No.:I005585）, also known as RO5045337, is an orally active and selective inhibitor of the interaction between p53 and MDM2. It demonstrates an HTRF (Homogeneous Time-Resolved Fluorescence) IC50 value of 18 nM, indicating its potency in disrupting the p53-MDM2 interaction. By inhibiting this interaction, RG7112 aims to restore p53 tumor-suppressor activity, which is often dysregulated in cancer. Its oral bioavailability makes it a promising candidate for the development of p53-targeted anticancer therapies.

Reference

1:Correction: Preclinical Efficacy of the MDM2 Inhibitor RG7112 in MDM2-Amplified and TP53 Wild-type Glioblastomas. [No authors listed]Clin Cancer Res. 2016 May 1;22(9):2313. doi: 10.1158/1078-0432.CCR-16-0703. No abstract available. PMID: 27141010 Free Article2:Preclinical Efficacy of the MDM2 Inhibitor RG7112 in MDM2-Amplified and TP53 Wild-type Glioblastomas. Verreault M, Schmitt C, Goldwirt L, Pelton K, Haidar S, Levasseur C, Guehennec J, Knoff D, Labussière M, Marie Y, Ligon AH, Mokhtari K, Hoang-Xuan K, Sanson M, Alexander BM, Wen PY, Delattre JY, Ligon KL, Idbaih A.Clin Cancer Res. 2016 Mar 1;22(5):1185-96. doi: 10.1158/1078-0432.CCR-15-1015. Epub 2015 Oct 19. PMID: 26482041 Free PMC Article3:Results of the Phase I Trial of RG7112, a Small-Molecule MDM2 Antagonist in Leukemia. Andreeff M, Kelly KR, Yee K, Assouline S, Strair R, Popplewell L, Bowen D, Martinelli G, Drummond MW, Vyas P, Kirschbaum M, Iyer SP, Ruvolo V, González GM, Huang X, Chen G, Graves B, Blotner S, Bridge P, Jukofsky L, Middleton S, Reckner M, Rueger R, Zhi J, Nichols G, Kojima K.Clin Cancer Res. 2016 Feb 15;22(4):868-76. doi: 10.1158/1078-0432.CCR-15-0481. Epub 2015 Oct 12. PMID: 26459177 Free PMC Article4:RG7112, a small-molecule inhibitor of MDM2, enhances trabectedin response in soft tissue sarcomas. Obrador-Hevia A, Martinez-Font E, Felipe-Abrio I, Calabuig-Fariñas S, Serra-Sitjar M, López-Guerrero JA, Ramos R, Alemany R, Martín-Broto J.Cancer Invest. 2015;33(9):440-50. doi: 10.3109/07357907.2015.1064534. Epub 2015 Aug 17. PMID: 26288114 5:RG7112, a Small-Molecule Inhibitor of MDM2, Enhances Trabectedin Response in Soft Tissue Sarcomas. Obrador-Hevia A, Martinez-Font E, Felipe-Abrio I, Calabuig-Fariñas S, Serra-Sitjar M, López-Guerrero JA, Ramos R, Alemany R, Martín-Broto J.Cancer Invest. 2015 Aug 17. [Epub ahead of print] PMID: 26279182 6:Clinical pharmacology characterization of RG7112, an MDM2 antagonist, in patients with advanced solid tumors. Patnaik A, Tolcher A, Beeram M, Nemunaitis J, Weiss GJ, Bhalla K, Agrawal M, Nichols G, Middleton S, Beryozkina A, Sarapa N, Peck R, Zhi J.Cancer Chemother Pharmacol. 2015 Sep;76(3):587-95. doi: 10.1007/s00280-015-2830-8. Epub 2015 Jul 26. PMID: 26210682 7:Discovery of RG7112: A Small-Molecule MDM2 Inhibitor in Clinical Development. Vu B, Wovkulich P, Pizzolato G, Lovey A, Ding Q, Jiang N, Liu JJ, Zhao C, Glenn K, Wen Y, Tovar C, Packman K, Vassilev L, Graves B.ACS Med Chem Lett. 2013 Apr 2;4(5):466-9. doi: 10.1021/ml4000657. eCollection 2013 May 9. PMID: 24900694 Free PMC Article8:The orally bioavailable MDM2 antagonist RG7112 and pegylated interferon α 2a target JAK2V617F-positive progenitor and stem cells. Lu M, Xia L, Li Y, Wang X, Hoffman R.Blood. 2014 Jul 31;124(5):771-9. doi: 10.1182/blood-2013-11-536854. Epub 2014 May 28. PMID: 24869939 Free PMC Article9:Activation of p53 by the MDM2 inhibitor RG7112 impairs thrombopoiesis. Iancu-Rubin C, Mosoyan G, Glenn K, Gordon RE, Nichols GL, Hoffman R.Exp Hematol. 2014 Feb;42(2):137-45.e5. doi: 10.1016/j.exphem.2013.11.012. Epub 2013 Dec 3. PMID: 24309210 10:MDM2 small-molecule antagonist RG7112 activates p53 signaling and regresses human tumors in preclinical cancer models. Tovar C, Graves B, Packman K, Filipovic Z, Higgins B, Xia M, Tardell C, Garrido R, Lee E, Kolinsky K, To KH, Linn M, Podlaski F, Wovkulich P, Vu B, Vassilev LT.Cancer Res. 2013 Apr 15;73(8):2587-97. doi: 10.1158/0008-5472.CAN-12-2807. Epub 2013 Feb 11. PMID: 23400593 Free Article