Name: Crenolanib (CP-868596)
Brand: Selleck Chemicals
SKU: S2730
Rating: 5 (100 reviews)

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Kwaliteitscontrole (Quality Control)

Batch: Zuiverheid: 99.99%

99.99

Gerelateerde doelwitten	EGFR VEGFR JAK FGFR PDGFR Src HIF HER2 FLT Bcr-Abl
Overig FLT3 Inhibitoren	UNC2025 Dovitinib (TKI-258) Dovitinib (TKI258) Lactate monohydrate Tandutinib (MLN518) ENMD-2076 KW-2449 AST-487 (NVP-AST487) TCS 359 G-749 FF-10101

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

Cellijnen	Assaytype	Concentratie	Incubatietijd	Activiteitsbeschrijving	PMID
A549 cells	Cell viability assay	3.9-1000 nM	72 h	a dose-dependent inhibition of cancer cell viability	25328409
MV4-11	Function assay			a decrease in mitochondrial matrix protein aconitase hydratase 2 (ACO2)	25328409
MV4-11	Cytotoxicity assay			Cytotoxicity against human MV4-11 cells expressing FLT3 ITD mutant, IC50=0.0015μM	31207462
MOLM13	Cytotoxicity assay			Cytotoxicity against human MOLM13 cells expressing FLT3 ITD mutant, IC50=0.0049μM	31207462
MV4-11	Cytotoxicity assay		72 hrs	Cytotoxicity in human MV4-11 cells assessed as inhibition of cellular viability incubated for 72 hrs by CellTiter-Blue assay, IC50=0.012μM	30742435
DAOY	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY 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
BT-37	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells	29435139
NB-EBc1	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells	29435139
U-2 OS	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for U-2 OS cells	29435139
Saos-2	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 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
BT-12	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells	29435139
Rh18	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 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
RD	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells	29435139
A673	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells)	29435139
DAOY	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for DAOY 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
SK-N-SH	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-SH cells	29435139
MV4-11	Cytotoxicity assay	0.5 to 5000 nM	2 to 8 hrs	Cytotoxicity in human MV4-11 cells assessed as inhibition of cellular viability at 0.5 to 5000 nM incubated for 2 to 8 hrs followed by compound washout by CellTiter-Glo luminescent assay	30742435
Klik om meer experimentele gegevens over cellijnen te bekijken

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

Molecuulgewicht	443.54	Formule	C₂₆H₂₉N₅O₂	Opslag (vanaf de datum van ontvangst)	3 jaar-20°Cpoeder
CAS-nr.	670220-88-9	SDF downloaden		Opslag van stamoplossingen	1 jaar-80°Cin oplosmiddel 1 maand-20°Cin oplosmiddel
Synoniemen	CP-868596, ARO 002			Smiles	CC1(COC1)COC2=CC3=C(C=C2)N(C=N3)C4=NC5=C(C=CC=C5N6CCC(CC6)N)C=C4

Oplosbaarheid (Solubility)

In vitro
Batch:

DMSO : 88 mg/mL (198.4 mM)
(Met vocht verontreinigd DMSO kan de oplosbaarheid verminderen. Gebruik verse, watervrije DMSO.)

Ethanol : 88 mg/mL

Water : 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.
Clear solution	30%PEG400 1 0.5%Tween80 2 5%propylene glycol Gevalideerd door Selleck labs. Mocht u aanpassingen aan deze formulering nodig hebben, neem dan contact op met ons verkoopteam voor aangepaste tests.	30.000mg/ml (67.64mM)	Taking the 1 mL working solution as an example, add 300 μL of 100 mg/ml clarified PEG400 stock solution to 5 μL of Tween80, mix evenly to clarify it; add 50 μL Propylene glycol to the above system, mix evenly to clarify it; then continue to add 645 μL 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.

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	FLT3 (CHO cells) 0.74 nM(Kd) PDGFRα (CHO cells) 2.1 nM(Kd) PDGFRβ (CHO cells) 3.2 nM(Kd)
In vitro	Crenolanib is significantly more potent in inhibiting the kinase activity of resistant PDGFRα kinases (D842I, D842V, D842Y, D1842-843IM, and deletion I843). This compound is more potent against D842V in the isogenic model system, with an IC50 of approximately 10 nM. It inhibits the kinase activity of the fusion oncogene in EOL-1 cell line, which is derived from a patient with chronic eosinophilic leukemia and expresses the constitutively activated FIP1L1- PDGFRα fusion kinase, with IC50 = 21 nM. This chemical also inhibits the proliferation of EOL-1 cells with IC50 = 0.2 pM. It inhibits the activation of V561D or D842V-mutant kinases expressed in BaF3 cells with IC50 with 85 nM or 272 nM, respectively. This compound inhibits PDGFRα activation in H1703 non-small cell lung cancer cell line which has 24-fold amplification of the 4q12 region that contains the PDGFRα locus, with IC50 with 26 nM. It is an orally bioavailable, highly potent and selective PDGFR TKI. This benzimidazole compound has IC50s of 0.9 nM and 1.8 nM for PDGFRA and PDGFRB, respectively.
Kinase Assay	Biochemische beoordeling van PDGFRα-kinaseactiviteit
Kinase Assay	Chinese hamsterovariumcellen (CHO) worden transiënte getransfecteerd met gemuteerde of wildtype PDGFRα-constructen en behandeld met verschillende concentraties Crenolanib. Experimenten met recombinant DNA worden uitgevoerd onder biosafety level 2-condities in overeenstemming met de richtlijnen. Eiwitlysaten van cellijnen worden bereid en onderworpen aan immunoprecipitatie met anti-PDGFRα-antilichamen, gevolgd door sequentiële immunoblotting voor PDGFRα. Densitometrie wordt uitgevoerd om het medicijneffect te kwantificeren met behulp van Photoshop-software, waarbij het niveau van fosfor-PDGFRα wordt genormaliseerd naar totaal eiwit. Densitometrie- en proliferatie-experimentele resultaten worden geanalyseerd met behulp van Calcusyn 2.1-software om de IC50-waarden mathematisch te bepalen. De Wilcoxon Rank Sum Test wordt gebruikt om de IC50-waarden van deze verbinding voor een gegeven mutatie te vergelijken.
In vivo	This compound, a PDGFR inhibitor, suppresses lung cancer cell proliferation and inhibits tumor growth in vivo
Referenties	[1] https://pubmed.ncbi.nlm.nih.gov/22745105/ [2] http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=37bcae41-860c-44f3-a18f-fe31ecc9581f&cKey [3] https://pubmed.ncbi.nlm.nih.gov/25328409/

Toepassingen (Applications)

Methoden	Biomarkers	Afbeeldingen	PMID
Western blot	pKIT / KIT pFLT3 / FLT3 / pERK / ERK / pS6 / S6 pAKT / AKT / pMAPK / MAPK / pSTAT5 / STAT5		24623852
Growth inhibition assay	Cell viability		24623852

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
NCT00949624	Completed	Advanced Solid Tumors	Arog Pharmaceuticals Inc.	December 2005	Phase 1

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C7=C6/X	C7:	LOG(C7):
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Crenolanib (CP-868596) PDGFR/FLT3-remmer

Molecuulgewicht: 443.54

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)

Crenolanib (CP-868596) PDGFR/FLT3-remmer

Molecuulgewicht: 443.54

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)

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