LY3039478

SKU: orb1226314

Description

LY3039478 (Crenigacestat) is an exquisitely potent inhibitor of Notch-1 intracellular domain (N1ICD) cleavage with IC50 of 1 nM, also potently inhibits mutant Notch receptor activity; inhibits N1ICD cleavage and expression of Notch-regulated genes in the tumor microenvironment in xenograft tumor models; significantly inhibits the growth of CCRCC cell lines in a concentration-dependent manne, decreases expression of Myc and cyclin A1, causes G0/G1 cell cycle arrest in CCRCC cells, demonstrates in vivo efficacy in CCRCC in mice model. Blood Cancer Phase 2 Clinical(In Vitro):Crenigacestat (100 nM) exhibits anti-cancer activity in K07074 cells (a primary mouse liver tumor cell line).Crenigacestat (LY3039478) decreases expression of Myc and cyclin A1 (part of the NOTCH-driven proliferative signature) in murine and human model systems. Crenigacestat (LY3039478) treatment also leads to G0/G1 cell cycle arrest in CCRCC cells.(In Vivo):Crenigacestat (8 mg/kg, oral gavage three times a week) resulted in significantly increases survival and delayed tumor growth in independent cohorts of mice demonstrating in vivo efficacy in CCRCC.

Key Properties

• CAS Number: 1421438-81-4
• MW: 464.4376
• Purity: >98% (HPLC)
• Formula: C₂₂H₂₃F₃N₄O₄
• SMILES: O=C(N[C@@H](C)C(N[C@H]1C2=CC=CC=C2C3=CC=CN=C3N(CCO)C1=O)=O)CCC(F)(F)F
• Target: Notch
• Solubility: DMSO: ≥ 34 mg/mL

Bioactivity

• In Vivo:
  Crenigacestat (8 mg/kg, oral gavage three times a week) resulted in significantly increases survival and delayed tumor growth in independent cohorts of mice demonstrating In vivo efficacy in CCRCC. Animal model: CCRCC xenografts were established in NOD-scid IL2R null mice with subcutaneous implantation using the 769-P cell line. Dosage: 8 mg/kg. Administration: Oral gavage three times a week. Result: Resulted in increased overall survival when compared with vehicle control in CCRCC xenografts.
• In Vitro:
  Crenigacestat (100 nM) exhibits anti-cancer activity in K07074 cells (a primary mouse liver tumor cell line). Crenigacestat (LY3039478) decreases expression of Myc and cyclin A1 (part of the NOTCH-driven proliferative signature) in murine and human model systems. Crenigacestat (LY3039478) treatment also leads to G0/G1 cell cycle arrest in CCRCC cells. Cell Viability Assay. Cell line: K07074 cells. Concentration: 100 nM. Incubation time: 24-96 hours. Result: Effectively reduced the growth of K07074 cells.

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

Crenigacestat | LY 3039478

Quick Database Links

Gene Symbol

Notch