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PLX4032 (Vemurafenib) B-Raf-remmer

Name: PLX4032 (Vemurafenib)
Brand: Selleck Chemicals
SKU: S1267
Rating: 5 (683 reviews)

Cat.Nr.S1267

Vemurafenib (PLX4032, RG7204, RO5185426) is een nieuwe en potente remmer van B-Raf^V600E met een IC50 van 31 nM in een celvrije test. 10-voudig selectief voor B-Raf^V600E boven wild-type B-Raf in enzymatische tests en de cellulaire selectiviteit kan 100-voudig overschrijden. Vemurafenib (PLX4032, RG7204) induceert autophagy.

PLX4032 (Vemurafenib) Raf remmer Chemical Structure

Chemische structuur

Moleculair gewicht: 489.92

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Kwaliteitscontrole

Batch: Zuiverheid: 99.98%

99.98

Gerelateerde doelwitten	ERK p38 MAPK JNK MEK Ras KRas S6 Kinase MAP4K TAK1 Mixed Lineage Kinase
Overige Raf Inhibitoren	LY3009120 Exarafenib (KIN-2787) GDC-0879 Avutometinib (Ro5126766, CH5126766) PLX-4720 AZ 628 SB590885 TAK-632 GW5074 RAF265 (CHIR-265)

Celkweek, behandeling & werkconcentratie

Cellijnen	Assaytype	Concentratie	Incubatietijd	Formulering	Activiteitsbeschrijving	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
Klik om meer experimentele gegevens over de cellijn te bekijken

Chemische informatie, Opslag en Stabiliteit

Moleculair gewicht	489.92	Formule	C₂₃H₁₈ClF₂N₃O₃S	Opslag (Vanaf de ontvangstdatum)	3 years -20°C(in the dark) powder 1 year -80°C(in the dark) in solvent
CAS-nr.	918504-65-1	SDF downloaden		Opslag van stamoplossingen	1 jaar-80°Cin oplosmiddel 1 maand-20°Cin oplosmiddel
Synoniemen	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

Oplosbaarheid

In vitro
Batch:

DMSO : 98 mg/mL (200.03 mM)
(Met vocht verontreinigde DMSO kan de oplosbaarheid verminderen. Gebruik verse, watervrije DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molariteitscalculator

Massa	Concentratie	Volume	Moleculair gewicht
=	×	×

Verdunningscalculator Moleculair gewicht calculator

In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 Corn oil Gevalideerd door Selleck labs. Mocht u aanpassingen aan deze formulering nodig hebben, neem dan contact op met ons verkoopteam voor aangepaste tests.	5.000mg/ml (10.21mM)	Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
Clear solution	2%DMSO 1 40%PEG300 2 5%TWEEN80 3 53%ddH2O Gevalideerd door Selleck labs. Mocht u aanpassingen aan deze formulering nodig hebben, neem dan contact op met ons verkoopteam voor aangepaste tests.	2.000mg/ml (4.08mM)	Taking the 1 mL working solution as an example, add 20 μL of 100 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 530 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	4%DMSO 1 30%PEG300 2 5%Tween80 3 61%ddH2O Gevalideerd door Selleck labs. Mocht u aanpassingen aan deze formulering nodig hebben, neem dan contact op met ons verkoopteam voor aangepaste tests.	1.250mg/ml (2.55mM)	Taking the 1 mL working solution as an example, add 40 μL of 31.25 mg/ml clarified DMSO stock solution to 300 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 610 μL of ddH2O to make it clear. Volume up to 1 mL. The mixed solution should be used immediately for optimal results.

In vivo Formuleringscalculator (Heldere oplossing)

Stap 1: Voer de onderstaande informatie in (Aanbevolen: Een extra dier voor het geval van verlies tijdens het experiment)

Dosering: mg/kg Gemiddeld gewicht van dieren: g Doseervolume per dier:μL Aantal dieren:

Stap 2: Voer de in vivo formulering in (Dit is alleen de calculator, geen formulering. Neem eerst contact met ons op als er geen in vivo formulering is in het gedeelte Oplosbaarheid.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Berekeningsresultaten:

Werkconcentratie: mg/ml;

Methode voor het bereiden van DMSO-mastervloeistof: mg geneesmiddel vooraf opgelost in μL DMSO ( Concentratie mastervloeistof mg/mL, Neem eerst contact met ons op als de concentratie de DMSO-oplosbaarheid van de partij geneesmiddel overschrijdt. )

Methode voor het bereiden van in vivo formulering: Neem μL DMSO mastervloeistof, voeg vervolgens toeμL PEG300, mengen en helder maken, voeg vervolgens toeμL Tween 80, mengen en helder maken, voeg vervolgens toe μL ddH₂O, mengen en helder maken.

Methode voor het bereiden van in vivo formulering: Neem μL DMSO mastervloeistof, voeg vervolgens toe μL Maïsolie, mengen en helder maken.

Opmerking: 1. Zorg ervoor dat de vloeistof helder is voordat u het volgende oplosmiddel toevoegt.
2. Zorg ervoor dat u het/de oplosmiddel(en) in de juiste volgorde toevoegt. U moet ervoor zorgen dat de verkregen oplossing, bij de vorige toevoeging, een heldere oplossing is voordat u verdergaat met het toevoegen van het volgende oplosmiddel. Fysische methoden zoals vortexen, echografie of een warmwaterbad kunnen worden gebruikt om het oplossen te bevorderen.

Werkingsmechanisme

Kenmerken	A novel and potent inhibitor of the B-RAF^V600E 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
In vitro	Vemurafenib (PLX4032) remt B-RAF^V600E, C-RAF, evenals wildtype B-RAF, met IC50 van respectievelijk 31 nM, 48 nM en 100 nM. Deze verbinding remt ook verschillende niet-RAF kinases, waaronder ACK1, KHS1 en SRMS, met IC50 van 18 nM tot 51 nM. In melanoomcellijnen hangt het remmende effect ervan af van de B-RAF-mutatiestatus, omdat het diegenen die B-RAF V600-mutanten bevatten, waaronder V600E, V600D, V600K en V600R, potent remt, maar niet wildtype of andere mutanten. De IC50-waarden op deze cellen, waaronder MALME-3M, Colo829, Colo38, A375, SK-MEL28 en A2058, variëren van 20 nM tot 1 μM. In deze cellen remt Vemurafenib (0,1 μM tot 30 μM) ook de fosforylering van zowel MEK1/2 als ERK1/2. Het is zeer effectief bij de behandeling van melanoom, vanwege zijn vermogen om B-RAF^V600E te remmen. Deze verbinding vertoont echter een beperkt effect bij patiënten met darmkanker die ook het B-RAF^V600E oncoproteïne dragen. De reden hiervoor is dat in darmkankercellen de B-RAF^V600E-remming door dit middel resulteert in een snelle feedback-EGFR-activering, die de PLX4032-geremde celproliferatie compenseert.
Kinase Assay	RAF-kinaseactiviteitsmetingen
Kinase Assay	De kinase-activiteiten van wild-type RAF en mutanten worden bepaald door de fosforylering van gebiotinyleerd-BAD-eiwit te meten in aanwezigheid van Vemurafenib (PLX4032). Voor elk enzym (0,01 ng) worden reacties van 20 μL uitgevoerd in 20 mM Hepes (pH 7,0), 10 mM MgCl₂, 1 mM DTT, 0,01% (v/v) Tween-20, 50 nM biotine-BAD-eiwit en 1 mM ATP bij kamertemperatuur. Reacties worden gestopt na 5 min met 5 μL van een oplossing die 20 mM Hepes (pH 7,0), 200 mM NaCl, 80 mM EDTA, 0,3% (w/v) runder serumalbumine (BSA) bevat. De stopoplossing bevat ook phospho-BAD (Ser112) antilichaam, streptavidine-gecoate donorbeads en eiwit A-acceptorbeads. Het antilichaam en de beads worden 30 min van tevoren in de stopoplossing in het donker bij kamertemperatuur geïncubeerd. De uiteindelijke verdunning van het antilichaam is 1/2000 en de uiteindelijke concentratie van elke bead is 10 μg/mL. De assayplaten worden een uur bij kamertemperatuur geïncubeerd en vervolgens afgelezen op een PerkinElmer AlphaQuest-lezer. Mutantactiviteiten zijn het gemiddelde van twee verschillende batches gezuiverd eiwit, dubbel geanalyseerd in drie verschillende experimenten.
In vivo	In B-RAF^V600E-mutante muizen-xenograftmodellen remt Vemurafenib (PLX4032) (6 mg/kg–20 mg/kg) de tumorgroei. In muizen-xenograftmodellen van LOX-, Colo829- en A375-cellen remt deze verbinding (12,5 mg/kg–100 mg/kg) de tumorgroei en verlengt de overleving van de muizen.
Referenties	[1] https://pubmed.ncbi.nlm.nih.gov/20823850/ [2] https://pubmed.ncbi.nlm.nih.gov/20551065/ [3] https://pubmed.ncbi.nlm.nih.gov/22281684/ [4] https://pubmed.ncbi.nlm.nih.gov/15808862/ [5] https://pubmed.ncbi.nlm.nih.gov/22180495/

Toepassingen

Methoden	Biomarkers	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	22448344
Growth inhibition assay	Cell viability	29179510
Immunofluorescence	uPAR / α5-β1 p-Akt(Thr308)	30611716

Informatie klinische proef

(gegevens van https://clinicaltrials.gov, bijgewerkt op 2024-05-22)

NCT-nummer	Rekrutering	Aandoeningen	Sponsor/Medewerkers	Startdatum	Fasen
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

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Vraag 1:
How about its half-life?

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

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

Antwoord:
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.

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