Home MAPK Raf inhibitor PLX4032 (Vemurafenib)

연구용

PLX4032 (Vemurafenib) B-Raf inhibitor

제품 번호: S1267

Vemurafenib (PLX4032, RG7204, RO5185426) is a novel and potent inhibitor of B-RafV600E with IC50 of 31 nM in cell-free assay. 10-fold selective for B-RafV600E over wild-type B-Raf in enzymatic assays and the cellular selectivity can exceed 100-fold. Vemurafenib (PLX4032, RG7204) induces autophagy.
PLX4032 (Vemurafenib) Raf inhibitor Chemical Structure

화학 구조

분자량: 489.92

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품질 관리 (Quality Control)

배치: 순도: 99.98%
99.98

세포 배양, 처리 및 작업 농도
(Cell Culture, Treatment & Working Concentration)

세포주 분석 유형 농도 배양 시간 제형 활성 설명 PMID
SKMEL19 Function Assay 6 μM 48 h DMSO Triggers ER stress 23362240
VMM12 Function Assay 3 μM 48 h DMSO Increases collagen synthesis and decreases IL-9 expression 25989506
C4 Function Assay 3 μM 48 h DMSO Increases collagen synthesis and decreases IL-8 expression 25989506
Calu-6 Function Assay 1 μM 1 h DMSO Activates MEK/ERK in cells with wild-type BRAF 20179705
PC Growth Inhibition Assay 96 h EC50> 1000 nM 19880792
TPC-1 (RET/PTC1) Growth Inhibition Assay 96 h EC50≥1000 nM 19880792
CAL62 (KRAS G12R) > 1000 > 1000 Growth Inhibition Assay 96 h EC50> 1000 nM 19880792
HTH7 (NRAS Q61R) Growth Inhibition Assay 96 h EC50≥ 1000 nM 19880792
C643 (HRAS G13R)≥ 500 Growth Inhibition Assay 96 h EC50 ≥ 500 nM 19880792
BCPAP (BRAF WT/V600E) Growth Inhibition Assay 96 h EC50=78 nM 19880792
BHT101 (BRAF WT/V600E) Growth Inhibition Assay 96 h EC50=97 nM 19880792
SW1736 (BRAF WT/V600E) Growth Inhibition Assay 96 h EC50=29 nM 19880792
8505C (BRAF V600E/V600E) Growth Inhibition Assay 96 h EC50=57 nM 19880792
ARO Function Assay 10 μM 72 h DMSO Induces the reexpression of the NIS pump 18458053
A375 Apoptosis Assay 10 μM DMSO Promotes apoptotic death 18458053
TPCI Growth Inhibition Assay 100 μM 96 h DMSO IC50=10.77 μM 18458053
ARO Growth Inhibition Assay 100 μM 96 h DMSO IC50=205 nM 18458053
NPA Growth Inhibition Assay 100 μM 96 h DMSO IC50=26 nM 18458053
A375 Growth Inhibition Assay 100 μM 96 h DMSO IC50=47 nM 18458053
UKF-NB-3 (ABCB1) Function Assay 1.25 µM 2 h DMSO Enhances accumulation of the fluorescent ABCB1 substrate rhodamine 123 24735766
UKF-NB-3 Function Assay 1.25 µM 2 h DMSO Significantly affects on accumulation of the fluorescent ABCB1 substrate rhodamine 123 24735766
A375 (BRAFV600E) Function Assay 8 h DMSO Increases intracellular ROS and NO levels 25363644
A375P Antiproliferative assay Antiproliferative activity against human A375P cells, IC50 = 0.254 μM. 22460030
A375 Antiproliferative assay Antiproliferative activity against human A375 cells expressing B-Raf V600E mutant and wild type Ras, IC50 = 0.31 μM. 22808911
A375P Antiproliferative assay 48 hrs Antiproliferative activity against human A375P cells after 48 hrs by MTT assay, IC50 = 0.25 μM. 24128410
A375 Cytotoxicity assay 72 hrs Cytotoxicity against human A375 cells after 72 hrs by MTT assay, IC50 = 0.18 μM. 24215818
SK-MEL-28 Cytotoxicity assay Cytotoxicity against human SK-MEL-28 cells expressing B-raf V600E mutant, IC50 = 0.1 μM. 24471466
M229 Cytotoxicity assay Cytotoxicity against human M229 cells expressing B-raf V600E mutant, IC50 = 0.1 μM. 24471466
M263 Cytotoxicity assay Cytotoxicity against human M263 cells expressing B-raf V600E mutant, IC50 = 0.1 μM. 24471466
M321 Cytotoxicity assay Cytotoxicity against human M321 cells expressing B-raf V600E mutant, IC50 = 0.1 μM. 24471466
M238 Cytotoxicity assay Cytotoxicity against human M238 cells expressing B-raf V600E mutant, IC50 = 0.1 μM. 24471466
M262 Cytotoxicity assay Cytotoxicity against human M262 cells expressing B-raf V600E mutant, IC50 = 0.1 μM. 24471466
M249 Cytotoxicity assay Cytotoxicity against human M249 cells expressing B-raf V600E mutant, IC50 = 0.1 μM. 24471466
M14 Cytotoxicity assay Cytotoxicity against human M14 cells expressing NRAS G12C mutant, IC50 = 0.15 μM. 24471466
SK-MEL-28 Antiproliferative assay 68 hrs Antiproliferative activity against human SK-MEL-28 cells harboring BRAF V600E mutant after 68 hrs by MTS assay, IC50 = 0.48 μM. 24588073
insect cell Function assay 60 mins Inhibition of full length human B-Raf V600E mutant expressed in baculovirus infected insect cells assessed as [gamma-33P]incorporation into MEK after 60 mins by scintillation counting, IC50 = 0.031 μM. 24900315
MALME-3M Function assay 1 hr Inhibition of B-Raf V600E mutant-mediated Erk phosphorylation in human MALME-3M cells after 1 hr by fluorescence analysis, IC50 = 0.061 μM. 24900315
A375 Function assay 1 hr Inhibition of B-Raf V600E mutant-mediated Erk phosphorylation in human A375 cells after 1 hr by fluorescence analysis, IC50 = 0.19 μM. 24900315
COLO205 Cytotoxicity assay 4 days Cytotoxicity against human COLO205 cells after 4 days by CellTiter-Glo assay, EC50 = 0.24 μM. 24900315
WM266.4 Antiproliferative assay 48 hrs Antiproliferative activity against human WM266.4 cells after 48 hrs by MTT assay, IC50 = 0.06 μM. 25267006
A375 Antiproliferative assay 48 hrs Antiproliferative activity against human A375 cells after 48 hrs by MTT assay, IC50 = 0.19 μM. 25267006
WM1361 Antiproliferative assay 48 hrs Antiproliferative activity against human WM1361 cells after 48 hrs by MTT assay, IC50 = 1.87 μM. 25267006
A375 Function assay Inhibition of B-raf V600E mutant in human A375 cells assessed as reduction in ERK1/2 phosphorylation incubated for 90 mins by Western blotting method, IC50 = 0.0331 μM. 25462267
A375 Antiproliferative assay 72 hrs Antiproliferative activity against human A375 cells after 72 hrs by CCK8 assay, IC50 = 3.315 μM. 25462267
SK-MEL-2 Function assay Inhibition of wild type B-raf in human SK-MEL-2 cells assessed as reduction in ERK1/2 phosphorylation incubated for 90 mins by Western blotting method 25462267
A375 Function assay 72 hrs Inhibition of BRAF V600E mutant in human A375 cells assessed as inhibition of ERK phosphorylation measured after 72 hrs by ELISA assay, IC50 = 0.15 μM. 25965804
A375 Antiproliferative assay 72 hrs Antiproliferative activity against human A375 cells after 72 hrs by resazurin assay, IC50 = 0.17 μM. 25965804
A375 Function assay 15 mins Competitive binding affinity to BRAF in human A375 cells after 15 mins in presence of ATP analogue, IC50 = 0.26 μM. 25965804
A375 Function assay 15 mins Competitive binding affinity to ARAF in human A375 cells after 15 mins in presence of ATP analogue, IC50 = 0.95 μM. 25965804
HCT116 Function assay Inhibition of KRAS G13D mutant in human HCT116 cells assessed as inhibition of ERK phosphorylation by ELISA, IC50 = 16.6 μM. 25965804
HCT116 Function assay 0.34 to 20000 nM Paradoxical activation of RAS/RAF/MEK signaling pathway in human HCT116 cells expressing wild type BRAF assessed as ERK phosphorylation at 0.34 to 20000 nM 25965804
NZM20 Antiproliferative assay 68 hrs Antiproliferative activity against human NZM20 cells expressing B-Raf V600E mutant isolated from New Zealand metastatic melanoma patient incubated for 68 hrs by SRB assay, IC50 = 0.024 μM. 26005530
NZM07 Antiproliferative assay 68 hrs Antiproliferative activity against human NZM07 cells expressing B-Raf V600E mutant isolated from New Zealand metastatic melanoma patient incubated for 68 hrs by SRB assay, IC50 = 0.036 μM. 26005530
A375 Antiproliferative assay 68 hrs Antiproliferative activity against human A375 cells expressing B-Raf V600E mutant incubated for 68 hrs by MTT assay, IC50 = 0.079 μM. 26005530
COLO205 Antiproliferative assay 68 hrs Antiproliferative activity against human COLO205 cells expressing B-Raf V600E mutant incubated for 68 hrs by MTT assay, IC50 = 0.309 μM. 26005530
SK-MEL-28 Antiproliferative assay 68 hrs Antiproliferative activity against human SK-MEL-28 cells expressing B-Raf V600E mutant incubated for 68 hrs by MTT assay, IC50 = 0.381 μM. 26005530
HT-29 Antiproliferative assay 68 hrs Antiproliferative activity against human HT-29 cells expressing B-Raf V600E mutant incubated for 68 hrs by MTT assay, IC50 = 0.601 μM. 26005530
SK-MEL-1 Antiproliferative assay 68 hrs Antiproliferative activity against human SK-MEL-1 cells expressing B-Raf V600E mutant incubated for 68 hrs by MTT assay, IC50 = 1.499 μM. 26005530
NZM40 Antiproliferative assay 68 hrs Antiproliferative activity against human NZM40 cells expressing wild type B-Raf isolated from New Zealand metastatic melanoma patient incubated for 68 hrs by SRB assay, IC50 = 3.01 μM. 26005530
NZM09 Antiproliferative assay 68 hrs Antiproliferative activity against human NZM09 cells expressing wild type B-Raf isolated from New Zealand metastatic melanoma patient incubated for 68 hrs by SRB assay, IC50 = 8.33 μM. 26005530
A375P Antiproliferative assay 72 hrs Antiproliferative activity against human A375P cells expressing BRAF V600E mutant after 72 hrs by CellTiter-Glo assay, IC50 = 0.37 μM. 26724730
BL21(DE3) Function assay Inhibition of N-terminal his-tagged BRAF V600E mutant (448 to 723 residues) (unknown origin) expressed in Escherichia coli BL21(DE3) cells assessed as phosphorylation of biotinylated-MEK by AlphaScreen assay, IC50 = 0.031 μM. 26852623
A375 Function assay 1 hr Inhibition of B-Raf V600E mutant in human A375 cells assessed as ERK phosphorylation preincubated for 1 hr by Western blot method, IC50 = 0.017 μM. 27085672
MIAPaCa2 Function assay 1 hr Inhibition of wild type B-Raf in human MIAPaCa2 cells assessed as reduction in ERK phosphorylation preincubated for 1 hr by Western blot method, EC50 = 2.29 μM. 27085672
COLO205 Cytotoxicity assay 72 hrs Cytotoxicity against human COLO205 cells harboring B-Raf V600E mutant assessed as growth inhibition after 72 hrs by MTT assay, IC50 = 0.044 μM. 27155899
HT-29 Cytotoxicity assay 72 hrs Cytotoxicity against human HT-29 cells harboring B-Raf V600E mutant assessed as growth inhibition after 72 hrs by MTT assay, IC50 = 0.156 μM. 27155899
HCT116 Cytotoxicity assay 72 hrs Cytotoxicity against human HCT116 cells harboring wild type B-Raf assessed as growth inhibition after 72 hrs by MTT assay, IC50 = 14.58 μM. 27155899
WM266.4 Antiproliferative assay 24 hrs Antiproliferative activity against human WM266.4 cells assessed as cell viability after 24 hrs by MTT assay, GI50 = 0.21 μM. 27238841
WM266.4 Antiproliferative assay 24 hrs Antiproliferative activity against human WM266.4 cells harboring BRAF V600E mutant assessed as cell growth inhibition after 24 hrs by MTT assay, IC50 = 0.07 μM. 27634195
A375 Antiproliferative assay 24 hrs Antiproliferative activity against human A375 cells assessed as cell growth inhibition after 24 hrs by MTT assay, IC50 = 0.21 μM. 27634195
WM1361 Antiproliferative assay 24 hrs Antiproliferative activity against human WM1361 cells assessed as cell growth inhibition after 24 hrs by MTT assay, IC50 = 1.86 μM. 27634195
SK-MEL-28 Antiproliferative assay 48 hrs Antiproliferative activity against human SK-MEL-28 cells harboring BRAF V600E mutant assessed as concentration required for total growth inhibition measured after 48 hrs resazurin assay, TGI = 2 μM. 27774137
SK-MEL-28 Growth inhibition assay 1 hr Growth inhibition of human SK-MEL-28 cells harboring BRAF V600E mutant preincubated for 1 hr followed by irradiation of 1.13 kW/m2 UV-light for 5 mins measured after 48 hrs resazurin assay 27774137
A375 Antiproliferative assay 72 hrs Antiproliferative activity human A375 cells after 72 hrs by cell titer-glo luminescence assay, IC50 = 0.7 μM. 28242553
COLO205 Antiproliferative assay 72 hrs Antiproliferative activity human COLO205 cells after 72 hrs by cell titer-glo luminescence assay, IC50 = 5.16 μM. 28242553
HepG2 Antiproliferative assay 72 hrs Antiproliferative activity human HepG2 cells after 72 hrs by cell titer-glo luminescence assay, IC50 = 5.48 μM. 28242553
SK-MEL-2 Antiproliferative assay 72 hrs Antiproliferative activity human SK-MEL-2 cells after 72 hrs by cell titer-glo luminescence assay, IC50 = 5.64 μM. 28242553
K562 Function assay 1 hr Stabilization of BRAF in human K562 cells after 1 hr by thermal shift assay, EC50 = 0.79433 μM. 28280261
K562 Function assay 1 hr Stabilization of FECH in human K562 cells after 1 hr by thermal shift assay, EC50 = 5.01187 μM. 28280261
A375M Antiproliferative assay 72 hrs Antiproliferative activity against human A375M cells harboring BRAF V600E mutant after 72 hrs by MTT assay, IC50 = 0.5 μM. 28458134
1205 Lu Antiproliferative assay 72 hrs Antiproliferative activity against human 1205 Lu cells harboring BRAF V600E mutant after 72 hrs by MTT assay, IC50 = 2 μM. 28458134
A375M Antiproliferative assay 48 hrs Antiproliferative activity against human A375M cells harboring BRAF V600E mutant after 48 hrs by MTT assay, IC50 = 2.05 μM. 28458134
UACC-903 Antiproliferative assay 72 hrs Antiproliferative activity against human UACC-903 cells harboring BRAF V600E mutant after 72 hrs by MTT assay, IC50 = 2.7 μM. 28458134
1205 Lu Antiproliferative assay 48 hrs Antiproliferative activity against human 1205 Lu cells harboring BRAF V600E mutant after 48 hrs by MTT assay, IC50 = 7.6 μM. 28458134
UACC-903 Antiproliferative assay 48 hrs Antiproliferative activity against human UACC-903 cells harboring BRAF V600E mutant after 48 hrs by MTT assay, IC50 = 12.3 μM. 28458134
CHL-1 Antiproliferative assay 72 hrs Antiproliferative activity against human CHL-1 cells harboring wild type BRAF after 72 hrs by MTT assay, IC50 = 12.7 μM. 28458134
CHL-1 Antiproliferative assay 48 hrs Antiproliferative activity against human CHL-1 cells harboring wild type BRAF after 48 hrs by MTT assay, IC50 = 20 μM. 28458134
HCT116 Function assay Stimulation of BRAF-CRAF dimerization in human HCT116 cells by luciferase complementation assay, EC50 = 0.601 μM. 28557458
Calu6 Function assay 3 uM 2 hrs Activation of CRAF in human Calu6 cells assessed as increase in MEK phosphorylation at 3 uM after 2 hrs by FRET assay 28557458
Sf9 Function assay 1 hr Inhibition of human ZAK (5 to 309 residues) expressed in baculovirus infected Sf9 insect cells using ZAKtide as substrate after 1 hr by mass spectrometry, IC50 = 0.023 μM. 28586211
Sf9 Function assay 30 mins Inhibition of N-terminal GST-tagged recombinant human full-length ZAK expressed in baculovirus infected Sf9 insect cells using MBP as substrate after 30 mins by ADP-Glo assay, IC50 = 0.0314 μM. 28586211
UACC-903 Cytotoxicity assay 25 uM 48 hrs Cytotoxicity against human UACC-903 cells assessed as cell viability at 25 uM after 48 hrs by MTT assay relative to control, IC50 = 3.6 μM. 29133035
CHL-1 Antiproliferative assay 72 hrs Antiproliferative activity against human CHL-1 cells harboring wild type BRAF after 72 hrs by MTT assay, IC50 = 13.7 μM. 29133035
A375 Function assay 96 hrs Inhibition of BRAF V600E mutant in human A375 cells assessed as reduction in cell proliferation incubated for 96 hrs by MTT assay, IC50 = 0.127 μM. 29407977
A375 Function assay Inhibition of BRAF V600E mutant in human A375 cells assessed as reduction in ERK phosphorylation by AlphaScreen assay, IC50 = 0.032 μM. 29461827
SK-MEL-32 Cytotoxicity assay Cytotoxicity against human SK-MEL-32 cells, IC50 = 0.31 μM. 29461827
WM266.4 Antiproliferative assay 48 hrs Antiproliferative activity against human WM266.4 cells after 48 hrs by MTT assay, GI50 = 0.21 μM. 29940463
A375 Antiproliferative assay 48 hrs Antiproliferative activity against human A375 cells after 48 hrs by MTT assay, GI50 = 0.95 μM. 29940463
HT-29 Antiproliferative assay 48 hrs Antiproliferative activity against human HT-29 cells after 48 hrs by MTT assay, GI50 = 1.88 μM. 29940463
WM1361 Antiproliferative assay 48 hrs Antiproliferative activity against human WM1361 cells after 48 hrs by MTT assay, GI50 = 20.8 μM. 29940463
HCT116 Antiproliferative assay 48 hrs Antiproliferative activity against human HCT116 cells after 48 hrs by MTT assay, GI50 = 25.2 μM. 29940463
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells 29435139
DAOY qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells 29435139
RD qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells 29435139
SK-N-SH qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells 29435139
MG 63 (6-TG R) qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells 29435139
NB1643 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells 29435139
OHS-50 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells) 29435139
U-2 OS qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for U-2 OS cells 29435139
Rh41 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh41 cells 29435139
SJ-GBM2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells 29435139
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells 29435139
LAN-5 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells 29435139
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-MC cells 29435139
TC32 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 cells 29435139
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화학 정보, 보관 및 안정성 (Chemical Information, Storage & Stability)

분자량 489.92 화학식

C23H18ClF2N3O3S

 보관 (수령일로부터) 3 years -20°C(in the dark) powder
1 year -80°C(in the dark) in solvent
CAS 번호 918504-65-1 SDF 다운로드 원액 보관

동의어 RG7204, RO5185426,PLX4032 Smiles CCCS(=O)(=O)NC1=C(C(=C(C=C1)F)C(=O)C2=CNC3=C2C=C(C=N3)C4=CC=C(C=C4)Cl)F

용해도 (Solubility)

In vitro
배치:

DMSO : 98 mg/mL (200.03 mM)
(수분으로 오염된 DMSO는 용해도를 감소시킬 수 있습니다. 신선하고 무수 DMSO를 사용하십시오.)

Water : Insoluble

Ethanol : Insoluble

몰농도 계산기

질량 농도 부피 분자량
희석 계산기 분자량 계산기

In vivo
배치:

생체 내 제형 계산기 (투명한 용액)

1단계: 아래 정보 입력 (권장: 실험 중 손실을 고려하여 추가 동물 포함)

mg/kg g μL

2단계: 생체 내 제형 입력 (이것은 계산기일 뿐 제형이 아닙니다. 용해도 섹션에 생체 내 제형이 없는 경우 먼저 당사에 문의하십시오.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

계산 결과:

작업 농도: mg/ml;

DMSO 원액 준비 방법: mg 약물 사전 용해 μL DMSO ( 원액 농도 mg/mL, 농도가 해당 약물 배치의 DMSO 용해도를 초과하는 경우 먼저 당사에 문의하십시오. )

생체 내 제형 준비 방법: 취하다 μL DMSO 원액, 다음 추가μL PEG300, 혼합하고 투명하게 한 다음 추가μL Tween 80, 혼합하고 투명하게 한 다음 추가 μL ddH2O, 혼합하고 투명하게 합니다.

생체 내 제형 준비 방법: 취하다 μL DMSO 원액, 다음 추가 μL 옥수수 기름, 혼합하고 투명하게 합니다.

참고: 1. 다음 용매를 추가하기 전에 액체가 투명한지 확인하십시오.
2. 용매를 순서대로 추가해야 합니다. 다음 용매를 추가하기 전에 이전 추가에서 얻은 용액이 투명한 용액인지 확인해야 합니다. 와동, 초음파 또는 뜨거운 물 중탕과 같은 물리적 방법을 사용하여 용해를 도울 수 있습니다.

작용 메커니즘 (Mechanism of Action)

특징
A novel and potent inhibitor of the B-RAFV600E oncoprotein.
Targets/IC50/Ki
SRMS
(Cell-free assay)
18 nM
ACK1
(Cell-free assay)
19 nM
B-Raf (V600E)
(Cell-free assay)
31 nM
C-Raf
(Cell-free assay)
48 nM
MAP4K5 (KHS1)
(Cell-free assay)
51 nM
FGR
(Cell-free assay)
63 nM
B-Raf
(Cell-free assay)
100 nM
LCK
(Cell-free assay)
183 nM
BRK
(Cell-free assay)
213 nM
NEK11
(Cell-free assay)
317 nM
BLK
(Cell-free assay)
547 nM
Lyn B
(Cell-free assay)
599 nM
YES1
(Cell-free assay)
604 nM
WNK3
(Cell-free assay)
877 nM
MNK2
(Cell-free assay)
1.717 μM
FRK (PTK5)
(Cell-free assay)
1.884 μM
CSK
(Cell-free assay)
2.339 μM
Src
(Cell-free assay)
2.389 μM
시험관 내(In vitro)
Vemurafenib (PLX4032) inhibits B-RAFV600E, C-RAF, as well as wildtype B-RAF, with IC50 of 31 nM, 48 nM and 100 nM, respectively. This compound also inhibits several non-RAF kinases, including ACK1, KHS1, and SRMS, with IC50 of 18 nM to 51 nM. In melanoma cell lines, the inhibitory effect by it depends on B-RAF mutational status, because it potently inhibits those harboring B-RAF V600 mutants, including V600E, V600D, V600K, and V600R, but not wildtype or other mutants. The IC50 values on these cells, including MALME-3M, Colo829, Colo38, A375, SK-MEL28, and A2058, ranges from 20 nM to 1 μM. In these cells, Vemurafenib (0.1 μM to 30 μM) also inhibits the phosphorylation of both MEK1/2 and ERK1/2. It is highly effective in the treatment of melanoma, for its ability of inhibiting B-RAFV600E. However, this compound displays limited effect in colon cancer patients that also carrying B-RAFV600E oncoprotein. The reason for this is that, in colon cancer cells, B-RAFV600E inhibition by it results in a rapid feedback EGFR activation, which compensates for the PLX4032-inhibited cell proliferation.
키나아제 분석
RAF kinase activity measurements
The kinase activities of wild-type RAF and mutants are determined by measuring phosphorylation of biotinylated-BAD protein in the presence of Vemurafenib (PLX4032). For each enzyme (0.01 ng), 20 μL reactions are carried out in 20 mM Hepes (pH 7.0), 10 mM MgCl2, 1 mM DTT, 0.01% (v/v) Tween-20, 50 nM biotin-BAD protein, and 1 mM ATP at room temperature. Reactions are stopped at 5 min with 5 μL of a solution containing 20 mM Hepes (pH 7.0), 200 mM NaCl, 80 mM EDTA, 0.3% (w/v) bovine serum albumin (BSA). The stop solution also includes phospho-BAD (Ser112) antibody, streptavidin-coated donor beads, and protein A acceptor beads. The antibody and beads are pre-incubated in stop solution in the dark at room temperature for 30 min. The final dilution of antibody is 1/2000 and the final concentration of each bead is 10 μg/mL. The assay plates are incubated at room temperature for one hour and then are read on a PerkinElmer AlphaQuest reader. Mutant activities are the average of two different batches of purified protein assayed in duplicate in three different experiments.
생체 내(In vivo)
In B-RAFV600E-mutant mice xenograft models, Vemurafenib (PLX4032) (6 mg/kg–20 mg/kg) inhibits tumor growth. In mice xenograft models of LOX, Colo829, and A375 cells, this compound (12.5 mg/kg–100 mg/kg) inhibits tumor growth and prolongs mice survival.
참조
  • [4] https://pubmed.ncbi.nlm.nih.gov/15808862/
  • [5] https://pubmed.ncbi.nlm.nih.gov/22180495/

적용 분야 (Applications)

방법 바이오마커 이미지 PMID
Western blot p-ERK / p-CRAF p-MEK(S217/221) / pAKT(T308) / p-AKT(S473) / p-P70 S6K(T389) / p-S6(Ser235-236) / P-4EB-P1 Bax / Bcl2 / Bcl-xl / BIM / Mcl1
S1267-WB1
22448344
Growth inhibition assay Cell viability
S1267-viability1
29179510
Immunofluorescence uPAR / α5-β1 p-Akt(Thr308)
S1267-IF2
30611716

임상시험 정보 (Clinical Trial Information)

(데이터 출처 https://clinicaltrials.gov, 업데이트 날짜 2024-05-22)

NCT 번호 모집 조건 스폰서/협력자 시작일 단계
NCT05768178 Recruiting
Solid Tumor|Haematological Malignancy|Melanoma|Thyroid Cancer Papillary|Ovarian Neoplasms|Colorectal Neoplasms|Laryngeal Neoplasms|Carcinoma Non-Small-Cell Lung|Glioma|Multiple Myeloma|Erdheim-Chester Disease|Thyroid Carcinoma Anaplastic
Cancer Research UK|University of Manchester|University of Birmingham|Royal Marsden NHS Foundation Trust|Hoffmann-La Roche
 March 1 2023 Phase 2|Phase 3
NCT05068752 Recruiting
Pancreas Cancer
HonorHealth Research Institute|Bayer|Genentech Inc.
 October 28 2021 Phase 2
NCT03410875 Active not recruiting
Hairy Cell Leukemia|Leukemia|Leukemia Hairy Cell
Memorial Sloan Kettering Cancer Center|Dana-Farber Cancer Institute|Yale University
 February 9 2018 Phase 2
NCT03013491 Completed
Solid Tumor|Lymphoma
CytomX Therapeutics
 January 2017 Phase 1|Phase 2

자주 묻는 질문 (Frequently Asked Questions)

질문 1:
How about its half-life?

답변:
It was reported that this compound has a half-life of 57 hours.

질문 2:
When prepared in 4% DMSO/30% PEG 300/5% Tween 80/ddH2O solutions, it forms a pellet down the tube?

답변:
When preparing this kind of vehicle, please dissolve it in DMSO clearly first. If it dissolves not readily, please sonicate and warm in the water bath at about 45 degree. Then add PEG and Tween. After they mixed homogeneously, then dilute with water.