Powder: -20°C for 3 years | In solvent: -80°C for 1 year
RG7112 (RO5045337) (RO5045337) is an orally bioavailable and selective p53-MDM2 inhibitor.
説明 | RG7112 (RO5045337) (RO5045337) is an orally bioavailable and selective p53-MDM2 inhibitor. |
ターゲット&IC50 | MDM2:11 nM(Kd) |
In vitro | In three wild-type p53 (HCT116, RKO, and SJSA1) cell lines, RG7112 selectively and dose-dependently inhibits cell growth. In cancer cells expressing wild-type p53, RG7112 activates the p53 pathway, and induces cell-cycle arrest and apoptosis. RG7112, both alone and combined with Peg-IFNα 2a, significantly decreases MPN colony-forming unit-granulocyte macrophage and burst-forming unit-erythroid numbers and preferentially eliminates the total number of JAKV617F(+) MPN hematopoietic progenitor cells. In addition, in MDM2-amplified liposarcoma cells, RG7112 significantly synergizes with Trabectedin. |
In vivo | In rats, RG7112 impairs thrombopoiesis via activation of p53. In the SJSA1 xenograft mouse model, RG7112 (200 mg/kg, p.o.) penetrates tumor cells and activate p53 and its 2 major functions, cell-cycle arrest and apoptosis. In nude mice bearing SJSA-1, and MHMn xenografts, RG7112 (100 mg/kg, p.o.) causes tumor regression. |
キナーゼ試験 | HTRF assay: Homogeneous time-resolved fluorescence (HTRF) assay measures the signal generated by 2 components when they are in close proximity. The p53–MDM2 binding assay uses a biotinylated peptide derived from the MDM2-binding domain of p53 and a truncated N-terminal portion of recombinant human GST-tagged MDM2 protein containing the p53-binding domain. Proteins for crystal structure studies are expressed in E. coli strain BL21 using the helper plasmid pUBS 520 coding for the lacIq repressor and the rare tRNAArg [AGA/AGG]. For crystallization, the frozen protein is thawed and concentrated to 9.8 mg/mL using a Centricon concentrator (3,000 MW cutoff). The complex is then formed by combining the protein with a slight molar excess of the inhibitor (stock solution is 100 mM in DMSO) and this solution is allowed to sit for 4 hours at 4°C. Cryopreserved crystals are used to collect diffraction data on beamline X8C at the National Synchrotron Light Source at Brookhaven National Laboratory. |
細胞研究 | Cell lines: Three wild-type p53 (HCT116,RKO,and SJSA1) and 2 mutant p53 (SW480 and MDA-MB-435) cell lines. Concentrations: ~5 μM. Incubation Time: 5 d. Method: Cell proliferation/viability is evaluated by the tetrazolium dye (MTT) assay.Cell growth kinetics are measured using the IncuCyte live cell imaging system.For cell-cycle analysis,cells are cultured in T75 flask with appropriate growth medium (106 cells/condition in 10 mL) and incubated overnight at 37°C.They are incubated with test compounds and processed. |
動物実験 | Animal Models: Nude mice bearing SJSA-1,MHMn,or LNCaP xenografts. Formulation: Suspended in 1% Klucel LF/0.1% Tween 80. Dosages: ~200 mg/kg. Administration: p.o. |
別名 | RG-7112, RG 7112, RO5045337 |
分子量 | 727.78 |
分子式 | C38H48Cl2N4O4S |
CAS No. | 939981-39-2 |
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Ethanol: 93 mg/mL (128 mM)
DMSO: 93 mg/mL (128 mM)
H2O: < 1 mg/mL (insoluble or slightly soluble)
You can also refer to dose conversion for different animals. 詳細
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Please see Inhibitor Handling Instructions for more frequently ask questions. Topics include: how to prepare stock solutions, how to store products, and cautions on cell-based assays & animal experiments, etc.
RG7112 939981-39-2 Apoptosis Ubiquitination E1/E2/E3 Enzyme Mdm2 E1 activating enzyme Inhibitor Ubiquitin conjugating enzyme Ubiquitin activating enzyme RG-7112 E3 ligating enzyme MDM-2/p53 Ubiquitin ligase E2 conjugating enzyme RG 7112 RO5045337 RO 5045337 inhibit RO-5045337 inhibitor