LGK974

SKU: orb1305261

Description

LGK974 (NVP-LGK974) is a potent and selective PORCN inhibitor that blocks Wnt signaling with an IC50 of 0.4 nM in TM3 cells. It has been investigated in clinical trials for cancers such as metastatic colorectal carcinoma and head and neck squamous cell carcinoma, based on preclinical in vivo and in vitro studies.

Research Area

Stem Cell & Developmental Biology

Key Properties

• CAS Number: 1243244-14-5
• MW: 396.44
• Purity: >99.99% (May vary between batches)
• Formula: C₂₃H₂₀N₆O
• SMILES: Cc1cc(ccn1)-c1ncc(CC(=O)Nc2ccc(cn2)-c2cnccn2)cc1C
• Target: Porcupine
• Solubility: DMSO:16.96 mg/mL (42.78 mM);10% DMSO+90% Corn Oil:3.3 mg/mL (8.32 mM);Ethanol:< 1 mg/mL (insoluble or slightly soluble)

Bioactivity

• Target IC50:
  Porcn:0.4 nM
• In Vivo:
  LGK-974 inhibits a range of tested Wnts, with IC50 values between 0.05 to 2.4 nM. In the PORCN radioligand binding assay, LGK-974 effectively displaces [3H]GNF-1331 with an IC50 of 1 nM and exhibits minimal cytotoxicity at 20 μM. It specifically inhibits the growth of RNF43 mutant cell lines HPAF-II, PaTu 8988S, and Capan-2.
• In Vitro:
  In both the MMTV-WNT1 mouse model of breast carcinoma and the human head and neck squamous cell carcinoma model (hn30), LGK-974 (3 mg/kg) inhibits the Wnt signaling pathway, leading to tumor regression without affecting mouse body weight. Additionally, LGK-974 (5 mg/kg, twice daily, orally) also suppresses the growth of RNF43-mutant pancreatic tumors (HPAF-II and Capan-2).
• Cell Research:
  Cells are plated in growth medium in a 96-well plate at a density of 6,000–12,000 cells per well and treated with DMSO or 1 μM LGK974. After 3 d, the cells are treated with fresh growth medium containing 20 μM EdU, which is included in the Click-iT EdU Alexa Fluor 488 HCS assay kit, and the plate was incubated for 2 h at 37 °C in a humidi ed atmosphere containing 5% CO2. Cells are xed with nal 4% (mass/vol) paraformaldehyde for 30 min, washed with PBS, permeabilized, and stained with 50 μg/mL Hoechst in PBS for 30 min. After wash, the cells are proceeded to EdU detection according to the instruction of Click-iT EdU assay kit. Triplet wells are performed for each condition. (Only for Reference)

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

LGK 974, LGK974, LGK-974, NVP-LGK 974, NVP-LGK974, NVP-LGK-974, WNT974, WNT-974, WNT 974, Porcn

Compound Identifiers

PubChem CID

46926973