LY3039478

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

LY3039478 (Crenigacestat) 是一种极其有效的 Notch-1 胞内结构域 (N1ICD) 裂解抑制剂，IC50 为 1 nM。

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.

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.

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.

Crenigacestat | LY 3039478

Wnt/Notch/Hedgehog

Notch

Notch-1

Cancer

Blood cancer

1421438-81-4

464.4376

C22H23F3N4O4

>98% (HPLC)

DMSO: ≥ 34 mg/mL

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

Butanamide, N-[(1S)-2-[[(7S)-6,7-dihydro-5-(2-hydroxyethyl)-6-oxo-5H-pyrido[3,2-a][3]benzazepin-7-yl]amino]-1-methyl-2-oxoethyl]-4,4,4-trifluoro-

(-20℃)

With Ice Pack

≥ 2 years