Nutlin-3a, also known as SML 0580, is an inhibitor of MDM2 (human homolog of murine double minute 2), which disrupts its interaction with p53, leading to the stabilization and activation of p53. Nutlin-3a activates the p53 pathway and efficiently induces apoptosis in tumours with amplified MDM2 gene and overexpression of MDM2 protein.
CAS Number: 675576-98-4
Molecular Weight: 581.49
Chemical Name: 4-((4S, 5R)-4, 5-bis(4-chlorophenyl)-2-(2-isopropoxy-4-methoxyphenyl)-4, 5-dihydro-1H-imidazole-1-carbonyl)piperazin-2-one
Appearance: Solid Power
Purity: ≥98% (or refer to the Certificate of Analysis)
Solubility: DMSO: 100 mg/mL(171.97 mM). Water: Insoluble.
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis
Storage Condition: Dry, dark and -20 oC for 1 year or refer to the Certificate of Analysis.
Shelf Life: ≥12 months if stored properly.
Stock Solution Storage: 0 - 4 oC for 1 month or refer to the Certificate of Analysis.
Drug Formulation: To be determined
HS Tariff Code: 382200
How to use
Nutlin-3a displaces p53 from the binding pocket of MDM2 and thereby releases p53 from inhibition and proteasomal degradation, leading to induction of its downstream targets, cell cycle arrest, and apoptosis. Seven days of incubation with 10 μM nutlin-3a led to >90% inhibition of NIH3T3 cells’ growth. Nutlin-3a stabilizes and activates p53, and induces p21 expression in a dose-dependent manner. Nutlin-3a effectively depletes the S-phase compartment to 0.2-2% and increases the G1- and G2/M-phase compartments. Nutlin-3a induces apoptosis in ~60% of SJSA-1 and MHMcells after 40 h, which increased further after 60 h (85% and 65%, respectively) .
Nutlin-3a suppresses xenograft growth in a dose-dependent fashion with the highest dose (200 mg/kg) showing a substantial tumor shrinkage . Nutlin-3 is a selective activator of the p53 pathway in vivo and highly efficacious against SJSA-1 osteosarcoma tumors. Tumors with wild-type p53 and mdm2 gene amplification will respond best to therapy with Nutlin-3a.
- Vassilev LT, et al. Science, 2004, 303(5659), 844-848.
- Ohnstad HO, et al. BMC Cancer, 2011, 11(211), 1-11.
- Tovar C, et al. Proc Natl Acad Sci U S A, 2006, 103(6), 1888-1893.
Products are for research use only. Not for human use.
Payment & Security
Your payment information is processed securely. We do not store credit card details nor have access to your credit card information.