PLX-4720

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

B-Raf V600E 的有效选择性抑制剂，IC50 为 13 nM。

A potent and selective inhibitor of B-Raf V600E with IC50 of 13 nM; dispalys 10-fold selectivity over wild-type B-Raf, and remarkably selective against a diverse panel of 70 other kinases; inhibits ERK phosphorylation in COLO25 cells with IC50 of 14 nM; induces cell cycle arrest and apoptosis exclusively in B-Raf(V600E)-positive cells. In B-Raf(V600E)-dependent tumor xenograft models; orally active.Skin Cancer Preclinical.

PLX-4720 displays >10 times selectivity against wild type B-Raf, and >100 times selectivity over other kinases such as Frk, Src, Fak, FGFR, and Aurora A with IC50 of 1.3-3.4 μM. PLX-4720 significantly inhibits the ERK phosphorylation in cell lines bearing B-RafV600E with IC50 of 14-46 nM, but not the cells with wild-type B-Raf. PLX-4720 significantly inhibits the growth of tumor cell lines bearing the B-RafV600E oncogene, such as COLO205, A375, WM2664, and COLO829 with GI50 of 0.31 μM, 0.50 μM, 1.5 μM, and 1.7 μM, respectively. In addition, PLX-4720 treatment at 1 μM induces cell cycle arrest and apoptosis exclusively in the B-RafV600E-positive 1205Lu cells, but not in the B-Raf wild-type C8161 cells. PLX-4720 treatment (10 μM) significantly induces > 14-fold expression of BIM in the PTEN+ cells, compared with the PTEN- cell lines (4-fold), giving an explanation of the resistance of PTEN- cells to PLX-4720-induced apoptosis.

Oral administration of PLX-4720 at 20 mg/kg/day induces significant tumor growth delays and regressions in B-RafV600E-dependent COLO205 tumor xenografts, without obvious adverse effects in mice even at dose of 1 g/kg. PLX-4720 at 100 mg/kg twice daily almost completely eliminates the 1205Lu xenografts bearing B-RafV600E, while has no activity against C8161 xenografts bearing wild-type B-Raf. The anti-tumor effects of PLX-4720 correlate with the blockade of MAPK pathway in those cells harboring the V600E mutation. PLX-4720 treatment at 30 mg/kg/day significant inhibits the tumor growth of 8505c xenografts by >90%, and dramatically decreases distant lung metastases.

PLX4720 | PLX 4720

MAPK/ERK Signaling

Raf

B-Raf|B-Raf(V600E)|BRK|C-Raf-1(Y340D/Y341D)|FRK

Cancer

Skin Cancer

918505-84-7

413.8262

C17H14ClF2N3O3S

>98% (HPLC)

10 mM in DMSO

CCCS(=O)(NC1=CC=C(F)C(C(C2=CNC3=NC=C(Cl)C=C32)=O)=C1F)=O

1-Propanesulfonamide, N-[3-[(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)carbonyl]-2,4-difluorophenyl]-

(-20℃)

With Ice Pack

≥ 2 years