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| | Nutlin 3a Basic information |
| Product Name: | Nutlin 3a | | Synonyms: | 4-[[(4S,5R)-4,5-bis(4-chlorophenyl)-4,5-dihydro-2-[4-methoxy-2-(1-methylethoxy)phenyl]-1H-imidazol-1-yl]carbonyl]-2-Piperazinone;Nutlin 3a;Nutlin-3a (chiral);2-Piperazinone, 4-[[(4S,5R)-4,5-bis(4-chlorophenyl)-4,5-dihydro-2-[4-methoxy-2-(1-methylethoxy)phenyl]-1H-imidazol-1-yl]carbonyl]-;4-[[(4S,5R)-4,5-Bis(4-chlorophenyl)-4,5-dihydro-2-[4-methoxy-2-(1-methylethoxy)phenyl]-1H-imidazol-1-yl]carbonyl]-2-piperazinone Nutlin 3a;Nutlin 3a
4-[[(4S,5R)-4,5-Bis(4-chlorophenyl)-4,5-dihydro-2-[4-methoxy-2-(1-methylethoxy)phenyl]-1H-imidazol-1-yl]carbonyl]-2-piperazinone;4-[[(4S,5R)-4,5-Bis(4-chlorophenyl)-2-(2-isopropoxy-4-methoxyphenyl)-4,5-dihydroimidazol-1-yl]carbonyl]piperazin-2-one;4-[[(4S,5R)-4,5-Bis(4-chlorophenyl)-4,5-dihydro-2- | | CAS: | 675576-98-4 | | MF: | C30H30Cl2N4O4 | | MW: | 581.49 | | EINECS: | | | Product Categories: | Inhibitors | | Mol File: | 675576-98-4.mol |  |
| | Nutlin 3a Chemical Properties |
| density | 1.36 | | storage temp. | -20°C | | solubility | DMSO: soluble5mg/mL, clear | | form | White powder | | pka | 14.35±0.20(Predicted) | | color | white to beige | | optical activity | [α]/D -140 to -155° (c=0.5, CDCl3) | | InChIKey | BDUHCSBCVGXTJM-WUFINQPMSA-N |
| Hazard Codes | Xn | | Risk Statements | 22 | | WGK Germany | 3 |
| | Nutlin 3a Usage And Synthesis |
| Description | Nutlin-3 is a novel small-molecule antagonist of the human homolog of mouse double minute (MDM2) that binds MDM2 in the p53-binding pocket and activates the p53 signaling pathway. | | Uses | Nutlin-3a has been used as a tumor suppressor p53(TP53) stabilizer and as an inhibitor of the mouse double minute 2 homolog (MDM2)–p53 interaction. | | Definition | ChEBI: Nutlin-3 is a stilbenoid. It is a small molecule inhibitor that targets p53-Mdm2 interaction. | | Biological Activity | nutlin-3 is a small-molecule inhibitor of mdm2 (mouse double minute 2) with ic50 value of 0.09μm [1].nutlin-3 binds mdm2 in the tp53-bindingpocket, thereby interfering with mdm2-directed tp53 degradation. this has been shown to cause cell cycle arrest, growth inhibitionand apoptosis in both solid tumors and lymphoid neoplasms.in mantle cell lymphoma(mcl), it is reported that nutlin-3 can inhibit cell growth and activate apoptosis in bothwt-tp53(ic50 of 1 to 10μm) and mt-tp53(ic50 of 22.5μm) cells [2].nutlin-3 can also effectcell cycle in gastric cancer cell lines. it induces g1 arrest inmkn-45 and snu-1 cell lines. in vitro assay shows nutlin-3can enhance the antitumoreffects of conventional chemotherapeutic agents in several gastric cancer cell lines. and in in vivo assay, nutlin-3 significantly inhibits the growth of xenograft tumors [3]. | | Biochem/physiol Actions | Nutlin-3a is a potent nongenotoxic drug. It acts as a tumor suppressor p53 (TP53) activator and stabilizer. | | target | MDM2 | | storage | Store at -20°C | | Mode of action | Nutlin-3 binds to the p53 binding pocket in MDM2 and inhibits the p53/MDM2 interaction, leading to stabilization of p53 and induction of p53-dependent cell cycle arrest or apoptosis. Nutlin-3 can also inhibit cancer cell migration and invasion in a p53-dependent manner, most likely through inhibition of RhoA and Rac1 activity. In addition to p53, Nutlin-3 also blocks the interaction of MDM2 with p73, E2F1, HIF-1α, resulting in increased apoptosis (p73, E2F1) and decreased VEGF production and decreased angiogenesis (HIF-1α). Nutlin-3 is predicted to block the interaction of MDM2 and Numb.
Molecular Mechanisms of the actions of Nutlin-3 | | References | [1] LYUBOMIR T. VASSILEV. In Vivo Activation of the p53 Pathway by Small-Molecule Antagonists of MDM2[J]. Science, 2004, 303 5659. DOI:10.1126/science.1092472.
[2] YOKO TABE. MDM2 antagonist nutlin-3 displays antiproliferative and proapoptotic activity in mantle cell lymphoma.[J]. Clinical Cancer Research, 2009, 15 3: 933-942. DOI:10.1158/1078-0432.CCR-08-0399.
[3] SHINJI ENDO. Potent in vitro and in vivo antitumor effects of MDM2 inhibitor nutlin-3 in gastric cancer cells[J]. Cancer Science, 2010, 102 3: 605-613. DOI:10.1111/j.1349-7006.2010.01821.x.
[4] HONG SHEN Carl G M. Pharmacologic activation of p53 by small-molecule MDM2 antagonists.[J]. Current pharmaceutical design, 2011, 17 6: 560-568. DOI:10.2174/138161211795222603. |
| | Nutlin 3a Preparation Products And Raw materials |
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