Name: LY3009120
Brand: Selleck Chemicals
SKU: S7842
Rating: 5 (55 reviews)

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Kwaliteitscontrole (Quality Control)

Batch: Zuiverheid: 99.08%

99.08

Gerelateerde doelwitten	ERK p38 MAPK JNK MEK Ras KRas S6 Kinase MAP4K TAK1 Mixed Lineage Kinase
Overig Raf Inhibitoren	Exarafenib (KIN-2787) GDC-0879 Avutometinib (Ro5126766, CH5126766) PLX-4720 AZ 628 SB590885 TAK-632 GW5074 RAF265 (CHIR-265) PLX7904

Celkweek, behandeling & werkzame concentratie
(Cell Culture, Treatment & Working Concentration)

Cellijnen	Assaytype	Concentratie	Incubatietijd	Activiteitsbeschrijving	PMID
A375	Antiproliferative assay		72 hrs	Antiproliferative activity against human A375 cells after 72 hrs by resazurin assay, IC50=0.0092μM.	25965804
A375	Function assay		15 mins	Competitive binding affinity to EphA2 in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.02μM.	25965804
A375	Function assay		15 mins	Competitive binding affinity to BRAF in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.031μM.	25965804
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=0.037μM.	25965804
A375	Function assay		15 mins	Competitive binding affinity to ZAK in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.039μM.	25965804
A375	Function assay		15 mins	Competitive binding affinity to CRAF in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.042μM.	25965804
A375	Function assay		15 mins	Competitive binding affinity to ARAF in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.044μM.	25965804
A375	Function assay		15 mins	Competitive binding affinity to p38 in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.061μM.	25965804
A375	Function assay		15 mins	Competitive binding affinity to FYN in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.091μM.	25965804
A375	Function assay		15 mins	Competitive binding affinity to MAP3K1 in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.098μM.	25965804
A375	Function assay		15 mins	Competitive binding affinity to EphB4 in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.1μM.	25965804
HCT116	Function assay			Inhibition of KRAS G13D mutant in human HCT116 cells assessed as inhibition of ERK phosphorylation by ELISA, IC50=0.15μM.	25965804
A375	Function assay			In vivo inhibition of BRAF V600E mutant in human A375 cells xenografted in po dosed NIH nude rat assessed as plasma concentration required to inhibit ERK phosphorylation by 50%, INH=0.165μM.	25965804
HCT116	Antiproliferative assay		67 hrs	Antiproliferative activity against human HCT116 cells after 67 hrs by resazurin assay, IC50=0.22μM.	25965804
A375	Function assay		15 mins	Competitive binding affinity to CSK in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.29μM.	25965804
A375	Function assay		15 mins	Competitive binding affinity to SRC in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.31μM.	25965804
A375	Function assay		15 mins	Competitive binding affinity to ABL in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.38μM.	25965804
A375	Function assay		15 mins	Competitive binding affinity to IRAK1 in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.39μM.	25965804
A375	Function assay		15 mins	Competitive binding affinity to GCN2 in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.45μM.	25965804
A375	Function assay		15 mins	Competitive binding affinity to JNK in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.47μM.	25965804
A375	Function assay		15 mins	Competitive binding affinity to MAP2K5 in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.8μM.	25965804
A375	Function assay		15 mins	Competitive binding affinity to KHS1 in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.97μM.	25965804
HCT116	Function assay	<100 nM		Paradoxical activation of RAS/RAF/MEK signaling pathway in human HCT116 cells expressing wild type BRAF assessed as ERK phosphorylation at <100 nM	25965804
A375	Function assay			Inhibition of desthiobiotin-ATP acylphosphate probe binding to B-Raf in human A375 cells by MS analysis, IC50=0.031μM.	30529543
A375	Function assay			Inhibition of desthiobiotin-ATP acylphosphate probe binding to C-Raf in human A375 cells by MS analysis, IC50=0.042μM.	30529543
A375	Function assay			Inhibition of desthiobiotin-ATP acylphosphate probe binding to A-Raf in human A375 cells by MS analysis, IC50=0.044μM.	30529543
MV4-11	Antiproliferative assay		72 hrs	Antiproliferative activity against human MV4-11 cells after 72 hrs by Cell-Titer Glo assay, IC50=0.1μM.	30529543
SK-MEL-2	Antiproliferative assay		72 hrs	Antiproliferative activity against human SK-MEL-2 cells after 72 hrs by Cell-Titer Glo assay, IC50=0.2μM.	30529543
A375	Antiproliferative assay		72 hrs	Antiproliferative activity against human A375 cells after 72 hrs by Cell-Titer Glo assay, IC50=0.3μM.	30529543
SW579	Antiproliferative assay		72 hrs	Antiproliferative activity against human SW579 cells after 72 hrs by Cell-Titer Glo assay, IC50=0.9μM.	30529543
HT-29	Antiproliferative assay		72 hrs	Antiproliferative activity against human HT-29 cells after 72 hrs by Cell-Titer Glo assay, IC50=0.9μM.	30529543
HepG2	Antiproliferative assay		72 hrs	Antiproliferative activity against human HepG2 cells after 72 hrs by Cell-Titer Glo assay, IC50=2.6μM.	30529543
Klik om meer experimentele gegevens over cellijnen te bekijken

Chemische informatie, opslag en stabiliteit (Chemical Information, Storage & Stability)

Molecuulgewicht	424.51	Formule	C₂₃H₂₉FN₆O	Opslag (vanaf de datum van ontvangst)	3 jaar-20°Cpoeder
CAS-nr.	1454682-72-4	SDF downloaden		Opslag van stamoplossingen	1 jaar-80°Cin oplosmiddel 1 maand-20°Cin oplosmiddel
Synoniemen	DP-4978			Smiles	CC1=CC(=C(C=C1C2=C(N=C3C(=C2)C=NC(=N3)NC)C)NC(=O)NCCC(C)(C)C)F

Oplosbaarheid (Solubility)

In vitro
Batch:

DMSO : 20 mg/mL (47.11 mM)
(Met vocht verontreinigd DMSO kan de oplosbaarheid verminderen. Gebruik verse, watervrije DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molariteitscalculator

Massa	Concentratie	Volume	Molecuulgewicht
=	×	×

Verdunningscalculator Molecuulgewichtcalculator

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.
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.

In vivo formulatiecalculator (heldere oplossing)

Stap 1: Voer onderstaande informatie in (Aanbevolen: een extra dier om rekening te houden met 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 de sectie oplosbaarheid.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Berekeningsresultaten:

Werkconcentratie: mg/ml;

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

Methode voor het bereiden van in vivo formulering: Neem μL DMSO moedervloeistof, voeg daarna toeμL PEG300, mengen en verhelderen, daarna toevoegenμL Tween 80, mengen en verhelderen, daarna toevoegen μL ddH₂O, mengen en verhelderen.

Methode voor het bereiden van in vivo formulering: Neem μL DMSO moedervloeistof, voeg daarna toe μL Maïsolie, mengen en verhelderen.

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. Fysieke methoden zoals vortexen, ultrasoon of een warmwaterbad kunnen worden gebruikt om het oplossen te bevorderen.

Werkingsmechanisme (Mechanism of Action)

Targets/IC₅₀/Ki	C-Raf (Cell-free assay) 4.3 nM BRAF(V600E) (Cell-free assay) 5.8 nM BRAF WT (Cell-free assay) 15 nM
In vitro	LY3009120 inhibits the cell growth of A375 and HCT116 cells with the IC50 of 9.2 and 220 μM, respectively. This compound inhibits the tyrosine kinase KDR with the IC50 of 3.9 μM.
Kinase Assay	Kinase-activiteitsmeting met behulp van KiNativ-assays
Kinase Assay	Verbindingen worden gescreend in A375-celysaten met behulp van de ATP-gebaseerde probe bij 5 µM. IC50-waarden worden gerapporteerd in micromolaire eenheden. Celpellets worden geresuspendeerd in vier volumes lysisbuffer [25 mM Tris pH 7,6, 150 mM NaCl, 1% CHAPS, 1% Tergitol NP-40 type, 1% v/v fosfatase-inhibitorcocktail II], gesoniceerd met een tipsonicator en gehomogeniseerd met een Dounce-homogenisator. Lysaten worden geklaard door centrifugatie bij 100.000 g gedurende 30 min. De geklaarde lysaten worden gefilterd door een 0,22 μM spuitfilter en gelfilterd in reactiebuffer [20 mM Hepes pH 7,8, 150 mM NaCl, 0,1% Triton X-100, 1% v/v fosfatase-inhibitorcocktail II]. Vervolgens wordt MnCl2 aan het lysaat toegevoegd tot een eindconcentratie van 20 mM vóór de inhibitorbehandeling en probe-labeling. De uiteindelijke inhibitorconcentraties die worden gebruikt voor IC50-bepalingen zijn 10, 1, 0,1 en 0,01 μM. ATP-competitie-experimenten worden uitgevoerd bij 1.000, 100, 10 en 1 μM ATP. Alle inhibitorbehandelingen worden uitgevoerd bij kamertemperatuur.
In vivo	In rats bearing BRAF V600E ST019VR PDX tumors, LY3009120 (15 or 30 mg/kg, p.o.) shows a dose-dependent tumor growth inhibition. In nude rats bearing A375 xenograft, single dose oral treatment with this compound (3 to 50 mg/kg, p.o.) shows a dose dependent inhibition of phospho-ERK, with a dose for 50% inhibition of phospho-ERK (EC50) of 4.36 mg/kg, with plasma concentration to achieve 50% inhibition of phospho-ERK (EC50) of 68.9 ng/mL or 165 nM.
Referenties	[1] https://pubmed.ncbi.nlm.nih.gov/25965804/ [2] https://pubmed.ncbi.nlm.nih.gov/21700206/

Toepassingen (Applications)

Methoden	Biomarkers	Afbeeldingen	PMID
Western blot	Beclin-1 / Mcl-1 / LC3 / p62 p-EGFR / EGFR / p-BRAF / BRAF / p-CRAF / CRAF / p-MEK / MEK / p-AKT / AKT		28382170

Informatie over klinische proeven (Clinical Trial Information)

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

NCT-nummer	Werving	Aandoeningen	Sponsor/medewerkers	Startdatum	Fasen
NCT02014116	Terminated	Neoplasms\|Neoplasm Metastasis\|Melanoma\|Carcinoma Non-Small-Cell Lung\|Colorectal Neoplasms	Eli Lilly and Company	November 26 2013	Phase 1

Veelgestelde vragen (Frequently Asked Questions)

Vraag 1:
I am trying to figure out solubility of this compound for in vivo studies. I need some details on the formulation and how it is made to dissolve the chemical?

Antwoord:
It can dissolve in 4% DMSO/30% PEG 300/5% Tween 80/ddH2O at 1 mg/ml clearly, and in 0.5% CMC Na at 30 mg/ml as a suspension.

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):

LY3009120 Raf Remmer

Molecuulgewicht: 424.51

Kwaliteitscontrole (Quality Control)

Celkweek, behandeling & werkzame concentratie
(Cell Culture, Treatment & Working Concentration)

Chemische informatie, opslag en stabiliteit (Chemical Information, Storage & Stability)

Oplosbaarheid (Solubility)

Molariteitscalculator

In vivo formulatiecalculator (heldere oplossing)

Werkingsmechanisme (Mechanism of Action)

Toepassingen (Applications)

Informatie over klinische proeven (Clinical Trial Information)

Veelgestelde vragen (Frequently Asked Questions)

LY3009120 Raf Remmer

Molecuulgewicht: 424.51

Kwaliteitscontrole (Quality Control)

Celkweek, behandeling & werkzame concentratie (Cell Culture, Treatment & Working Concentration)

Chemische informatie, opslag en stabiliteit (Chemical Information, Storage & Stability)

Oplosbaarheid (Solubility)

Molariteitscalculator

In vivo formulatiecalculator (heldere oplossing)

Werkingsmechanisme (Mechanism of Action)

Toepassingen (Applications)

Informatie over klinische proeven (Clinical Trial Information)

Veelgestelde vragen (Frequently Asked Questions)

Celkweek, behandeling & werkzame concentratie
(Cell Culture, Treatment & Working Concentration)