LCL161

SKU: orb1227172

Description

LCL161, a SMAC mimetic, potently binds to and inhibits multiple IAPs (i.e. XIAP, c-IAP). Phase 2.(In Vitro):LCL161 shows anti-proliferative effects and reduces cell viability significantly in Hep3B (IC50=10.23 μM) and PLC5 (IC50=19.19 μM) cells in a dose-dependent manner. LCL161 induces apoptosis significantly in both the sensitive cell lines in a dose-dependent manner. LCL161 significantly down regulates the expression of cIAP1, starting at very low concentrations. LCL161 at low concentrations inhibits cIAP1 starting at the concentration of 0.5 nM. LCL161 is a small molecule oral IAP antagonist in development for use in combination with cytotoxic agents. The effect of LCL161 on CYP3A4/5 (CYP3A) activity is investigated in vitro. Results in human liver microsomes indicated LCL161 inhibited CYP3A in a concentration- and time-dependent manner (KI of 0.797 μM and Kinact of 0.0803 min-1). LCL161 activates human PXR in a reporter gene assay and induced CYP3A4 mRNA up to ~5-fold in human hepatocytes.(In Vivo):Tumor-bearing mice are treated with vehicle or LCL161 p.o. at a dose of 50 mg/kg/day, or SC-2001 p.o. at a dose of 10 mg/kg/day, 5 days a week, or in combination for the duration of the study. Tumor growth is significantly inhibited by co-treatment with SC2001 and LCL161 and tumor size in the co-treatment group is only one third of that of the control group at the end of the study. LCL161 is a first-in-class oral Smac mimetic shown to induce degradation of cIAP1 and cleavage of caspase 3 in mouse xenograft models.

Key Properties

• CAS Number: 1005342-46-0
• MW: 500.63
• Purity: >98% (HPLC)
• Formula: C₂₆H₃₃FN₄O₃S
• SMILES: C[C@H](NC)C(N[C@@H](C1CCCCC1)C(N2[C@H](C3=NC(C(C4=CC=C(F)C=C4)=O)=CS3)CCC2)=O)=O
• Target: IAP
• Solubility: Ethanol: 20 mg/mL warmed (39.94 mM); DMSO: 100 mg/mL (199.74 mM)

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

NVP-LCL161

Quick Database Links

Gene Symbol

IAP