L-779450

Research use only, not for human use.

L-779450 is a potent, ATP-competitive Raf kinase inhibitor with IC50 of 10 nM.

L-779450 is a potent, ATP-competitive Raf kinase inhibitor with IC50 of 10 nM, displays >7, >30 and >70-fold selectivity over p38α, GSK3β and Lck respectively; suppresses DNA synthesis and induced apoptosis in hematopoietic FDC-P1 cells transformed to grow in response to either Raf-1 or A-Raf, L-779,450 is less effective on B-Raf- or MEK1-responsive cells, also suppresses DNA synthesis and induces apoptosis in Raf-responsive cells and the effects are more significant on Raf-responsive compared to cytokine-mediated growth.

L-779450 (L-779,450) shows a high degree of specificity towards Raf. The only other tested kinase inhibited is p38MAPK, which has a kinase domain structurally related to Raf. L-779450 inhibits anchorage-independent growth of human tumor lines at doses ranging from 0.3 to 2?μM. The effects of L-779450 (L-779,450) on TRAIL sensitivity are investigated here in melanoma cell lines with high TRAIL sensitivity (A-375 and SK-Mel-147), moderate sensitivity (Mel-HO, SK-Mel-13, and SK-Mel-28), and permanent resistance (MeWo, Mel-2a, and SK-Mel-103), as well as in TRAIL-selected cell lines with acquired resistance (A-375-TS and Mel-HO-TS). Despite only moderate direct effects of L-779450 on apoptosis, it strongly enhances TRAIL-induced apoptosis in sensitive melanoma cells and overrules TRAIL resistance in Mel-2a, SK-Mel-103, A-375-TS, and Mel-HO-TS. At 24?hours, 16-35% apoptosis induction is obtained.

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L779450

MAPK/ERK Signaling

Raf

Raf

Cancer

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303727-31-3

347.7977

C20H14ClN3O

>98% (HPLC)

DMSO: ≥ 34 mg/mL

OC1=CC(C2=C(C3=CC=NC=C3)NC(C4=CC=CC=C4)=N2)=CC=C1Cl

Phenol, 2-chloro-5-[2-phenyl-4-(4-pyridinyl)-1H-imidazol-5-yl]-

(-20℃)

With Ice Pack

≥ 2 years