| Identification | Back Directory | [Name]
[(4R,5S)-4,5-Bis(4-chlorophenyl)-2-[4-(1,1-dimethylethyl)-2-ethoxyphenyl]-4,5-dihydro-4,5-dimethyl-1H-imidazol-1-yl][4-[3-(methylsulfonyl)propyl]-1-piperazinyl]methanone | [CAS]
939981-39-2 | [Synonyms]
RG7112
CS-2164
p53 inhibitor
RG7112;RG 7112
RG7112(RO5045337)
RO5045337 (RG7112)
p53 and MDM2 proteins-interaction-inhibitor
[(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
[(4R,5S)-4,5-Bis(4-chlorophenyl)-2-[4-(1,1-dimethylethyl)-2-ethoxyphenyl]-4,5-dihydro-4,5-dimethyl-1H-imidazol-1-yl][4-[3-(methylsulfonyl)propyl]-1-piperazinyl]methanone
Methanone, [(4S,5R)-4,5-bis(4-chlorophenyl)-2-[4-(1,1-diMethylethyl)-2-ethoxyphenyl]-4,5-dihydro-4,5-diMethyl-1H-iMidazol-1-yl][4-[3-(Methylsulfonyl)propyl]-1-piperazinyl]- | [Molecular Formula]
C38H48Cl2N4O4S | [MDL Number]
MFCD29905459 | [MOL File]
939981-39-2.mol | [Molecular Weight]
727.78 |
| Chemical Properties | Back Directory | [density ]
1.23 | [storage temp. ]
Store at -20°C | [solubility ]
≥36.4 mg/mL in DMSO; insoluble in H2O; ≥31.87 mg/mL in EtOH | [form ]
solid | [color ]
White to off-white | [InChIKey]
QBGKPEROWUKSBK-QPPIDDCLSA-N | [SMILES]
C(N1C(C2=CC=C(C(C)(C)C)C=C2OCC)=N[C@](C2=CC=C(Cl)C=C2)(C)[C@]1(C1=CC=C(Cl)C=C1)C)(N1CCN(CCCS(C)(=O)=O)CC1)=O |
| Hazard Information | Back Directory | [Description]
RG-7112 is an inhibitor of mouse double-minute 2 protein (MDM2; IC50 = 0.018 μM), an E3 ubiquitin ligase that ubiquitinates the tumor suppressor p53 and also acts as a negative regulator of p53 transcriptional activity.1 RG-7112 binds to the p53 binding pocket of MDM2. It increases the levels of p53 and its transcriptional targets in SJSA-1 osteosarcoma cells.1,2 It inhibits proliferation in cancer cell lines expressing wild-type p53 (IC50s = 0.18-2.2 μM) and cell lines expressing mutant p53 (IC50s = 5.7-20.3 μM). RG-7112 also prevents and reduces tumor growth in an SJSA-1 mouse xenograft model when administered at doses of 50 and 100 mg/kg per day, respectively.2 However, it inhibits thrombopoiesis in vivo, decreasing platelet counts in rats when administered at doses of 50 and 100 mg/kg and in cynomolgus monkeys at doses of 10 and 20 mg/kg.3 | [Uses]
RG 7112 is MDM2 antagonist. It can be used in biological study of single mouse analysis on evaluation of alternative in vivo drug screening methodology. | [in vivo]
RG7112 (25-200 mg/kg, single oral dose) activates p53 pathway and induces apoptosis in tumor cells in vivo[2].
?
RG7112 (100 mg/kg, gavage once per day, 5 days/week for 3 weeks ) reduces tumor growth rate and increases survival in GBM models[3]. | Animal Model: | Female Balb/c nude mice[2]. | | Dosage: | 25-200 mg/kg. | | Administration: | Orally, single dose. | | Result: | At the highest dose level of RG7112 (200 mg/kg) only 1.2% (± 0.89 SD) of cells incorporated BrdU at 24 h post-dosing, vs. 14% (± 1.83 SD) of vehicle treated tumors.
|
| Animal Model: | GBM cells were implanted into the brain of Athymic Nude mice (7 weeks old females, 10 animals/group)[3]. | | Dosage: | 100 mg/kg. | | Administration: | Oral gavage, once per day, 5 days/week for 3 weeks. | | Result: | Reduced tumor growth rate and increases survival in heterotopic and orthotopic animal models bearing MDM2-amplified GBM. |
| [target]
MDM2 | [References]
[1] BINH VU*. Discovery of RG7112: A Small-Molecule MDM2 Inhibitor in Clinical Development[J]. ACS Medicinal Chemistry Letters, 2013, 4 5: 466-469. DOI: 10.1021/ml4000657
[2] CHRISTIAN TOVAR. MDM2 small-molecule antagonist RG7112 activates p53 signaling and regresses human tumors in preclinical cancer models.[J]. Cancer research, 2013, 73 8: 2587-2597. DOI: 10.1158/0008-5472.can-12-2807
[3] CAMELIA IANCU-RUBIN . Activation of p53 by the MDM2 inhibitor RG7112 impairs thrombopoiesis[J]. Experimental hematology, 2014, 42 2: Pages 137-145.e5. DOI: 10.1016/j.exphem.2013.11.012 |
|
| Company Name: |
NCE Biomedical Co.,Ltd.
|
| Tel: |
4000-027-021 |24 +86-13986109188 | +86-15623472865 | +81-08033611988 |
| Website: |
www.chemicalbook.com/ShowSupplierProductsList15748/0_EN.htm |
|