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Ceritinib ALK remmer

Name: Ceritinib
Brand: Selleck Chemicals
SKU: S7083
Rating: 5 (118 reviews)

Cat.Nr.S7083

Ceritinib is een krachtige remmer tegen ALK met een IC50 van 0,2 nM in celvrije assays. Deze verbinding remt ook IGF-1R, InsR, STK22D en FLT3 met respectievelijk een IC50 van 8 nM, 7 nM, 23 nM en 60 nM. Fase 3.

Chemische structuur

Moleculair gewicht: 558.14

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Kwaliteitscontrole

Batch: Zuiverheid: 99.96%

99.96

Gerelateerde doelwitten	EGFR VEGFR PDGFR FGFR c-Met Src MEK CSF-1R FLT3 HER2
Overige ALK Inhibitoren	TAE684 (NVP-TAE684) GSK1838705A Repotrectinib (TPX-0005) AZD3463 Ensartinib dihydrochloride AP26113-analog (ALK-IN-1) ASP3026 NVL-655 (Neladalkib) Envonalkib Belizatinib (TSR-011)

Celkweek, behandeling & werkconcentratie

Cellijnen	Assaytype	Concentratie	Incubatietijd	Formulering	Activiteitsbeschrijving	PMID
Parental(+IL3)	Growth Inhibition Assay		72 h	DMSO	IC50=1586 ± 173 nM	25749034
WT 70	Growth Inhibition Assay		72 h	DMSO	IC50=21 ± 8 nM	25749034
G1128S 1022	Growth Inhibition Assay		72 h	DMSO	IC50=102 ± 38 nM	25749034
C1156F 1293	Growth Inhibition Assay		72 h	DMSO	IC50=217 ± 115 nM	25749034
I1171N 519	Growth Inhibition Assay		72 h	DMSO	IC50=187 ± 87 nM	25749034
I1171T 445	Growth Inhibition Assay		72 h	DMSO	IC50=82 ± 12 nM	25749034
F1174I 184	Growth Inhibition Assay		72 h	DMSO	IC50=13 ± 0.1 nM	25749034
N1178H 169	Growth Inhibition Assay		72 h	DMSO	IC50=42 ± 6 nM	25749034
E1210K 748	Growth Inhibition Assay		72 h	DMSO	IC50=187 ± 84 nM	25749034
C1156F/D1203N 2809	Growth Inhibition Assay		72 h	DMSO	IC50=254 ± 99 nM	25749034
Ba/F3 NA WT	Growth Inhibition Assay		72 h		IC50=0.020 μM	25727400
Ba/F3 NA C1156Y	Growth Inhibition Assay		72 h		IC50=0.071 μM	25727400
Ba/F3 NA L1196M	Growth Inhibition Assay		72 h		IC50=0.042 μM	25727400
Ba/F3 NA L1152R	Growth Inhibition Assay		72 h		IC50=0.288 μM	25727400
Ba/F3 NA G1202R	Growth Inhibition Assay		72 h		IC50=0.277 μM	25727400
Ba/F3 NA G1269A	Growth Inhibition Assay		72 h		IC50=0.019 μM	25727400
Ba/F3 NA S1206Y	Growth Inhibition Assay		72 h		IC50=0.037 μM	25727400
Ba/F3 EA WT	Growth Inhibition Assay		72 h		IC50=0.021 μM	25727400
Ba/F3 EA C1156Y	Growth Inhibition Assay		72 h		IC50=0.026 μM	25727400
Ba/F3 EA L1196M	Growth Inhibition Assay		72 h		IC50=0.019 μM	25727400
Ba/F3 EA L1152R	Growth Inhibition Assay		72 h		IC50=0.099 μM	25727400
Ba/F3 EA G1202R	Growth Inhibition Assay		72 h		IC50=0.467 μM	25727400
Ba/F3 EA G1269A	Growth Inhibition Assay		72 h		IC50=0.033 μM	25727400
Ba/F3 EA S1206Y	Growth Inhibition Assay		72 h		IC50=0.038 μM	25727400
BAF3	Antiproliferative assay		72 hrs		Antiproliferative activity against mouse BAF3 cells harboring EML4-ALK after 72 hrs by SRB or CCK8 assay, IC50 = 0.0107 μM.	29288940
NCI-H3122	Antiproliferative assay		72 hrs		Antiproliferative activity against human NCI-H3122 cells after 72 hrs by CellTiter-Glo Luminescent Cell Viability Assay, EC50 = 0.015 μM.	26568289
NCI-H2228	Growth inhibition assay		3 days		Growth inhibition of human NCI-H2228 cells after 3 days by luminescence-based CellTiter-Glo assay, IC50 = 0.015 μM.	29627725
SU-DHL1	Growth inhibition assay		3 days		Growth inhibition of human SU-DHL1 cells after 3 days by luminescence-based CellTiter-Glo assay, IC50 = 0.015 μM.	29627725
DFCI114	Antiproliferative assay		72 hrs		Antiproliferative activity against human DFCI114 cells expressing EML4-ALK G1269A mutant after 72 hrs by CellTiter-Glo Luminescent Cell Viability Assay, EC50 = 0.018 μM.	26568289
HCC78	Cytotoxicity assay		72 hrs		Cytotoxicity against human HCC78 cells harboring SLC34A2-ROS1 assessed as reduction in cell proliferation after 72 hrs by MTT assay, IC50 = 0.018 μM.	27474925
KARPAS299	Cytotoxicity assay		2 to 3 days		Cytotoxicity against human KARPAS299 cells after 2 to 3 days by luciferase reporter gene assay, IC50 = 0.0228 μM.	23742252
KARPAS299	Cytotoxicity assay				Cytotoxicity against human KARPAS299 cells expressing NPM-ALK fusion gene assessed as growth inhibition, IC50 = 0.0228 μM.	23837797
NCI-H3122	Function assay		72 hrs		Inhibition of EML4 fused ALK in human NCI-H3122 cells assessed as cell growth inhibition measured after 72 hrs by SRB assay, CC50 = 0.025 μM.	27915169
BAF3	Function assay		2 to 3 days		Inhibition of NPM-fused ALK (unknown origin) expressed in mouse BAF3 cells after 2 to 3 days by luciferase reporter gene assay, IC50 = 0.026 μM.	23742252
BA/F3	Cytotoxicity assay				Cytotoxicity against mouse BA/F3 cells expressing NPM-ALK fusion gene assessed as growth inhibition, IC50 = 0.026 μM.	23837797
KARPAS299	Antiproliferative assay		72 hrs		Antiproliferative activity against human KARPAS299 cells harboring NPM-ALK after 72 hrs by MTT assay, IC50 = 0.026 μM.	29174809
NCI-H2228	Antiproliferative assay		72 hrs		Antiproliferative activity against human NCI-H2228 cells harboring EML4-ALK after 72 hrs by MTT assay, IC50 = 0.026 μM.	30223120
KARPAS299	Cytotoxicity assay		72 hrs		Cytotoxicity against human KARPAS299 cells harboring NPM-ALK assessed as reduction in cell proliferation after 72 hrs by MTT assay, IC50 = 0.027 μM.	27474925
Ba/F3	Function assay		72 hrs		Inhibition of EML4-ALK S1206Y mutant (unknown origin) expressed in mouse Ba/F3 cells assessed as cell viability after 72 hrs by MTS assay, IC50 = 0.033 μM.	26568289
NCI-H3122	Antiproliferative assay				Antiproliferative activity against wild type human NCI-H3122 cells, CC50 = 0.038 μM.	26235945
NCI-H3122	Function assay		72 hrs		Inhibition of EML4-ALK in human NCI-H3122 cells assessed as inhibition of cell proliferation after 72 hrs by SRB assay, CC50 = 0.038 μM.	26923695
NCI-H3122	Function assay		72 hrs		Inhibition of EML4-ALK in human NCI-H3122 cells assessed as inhibition of cell proliferation after 72 hrs by SRB assay, CC50 = 0.038 μM.	26923695
NCI-H3122	Function assay		72 hrs		Inhibition of EML4 fused ALK in human NCI-H3122 cells assessed as cell growth inhibition after 72 hrs by SRB assay, CC50 = 0.038 μM.	28385505
BA/F3	Function assay				Inhibition of ALK (unknown origin) transfected in mouse BA/F3 cells, IC50 = 0.0407 μM.	23837797
Ba/F3	Function assay		72 hrs		Inhibition of wild type EML4-ALK (unknown origin) expressed in mouse Ba/F3 cells assessed as cell viability after 72 hrs by MTS assay, IC50 = 0.041 μM.	26568289
Ba/F3	Function assay		72 hrs		Inhibition of wild type EML4-ALK (unknown origin) expressed in mouse Ba/F3 cells assessed as cell viability after 72 hrs by MTS assay, IC50 = 0.041 μM.	26568289
KARPAS299	Antiproliferative assay		72 hrs		Antiproliferative activity against human KARPAS299 cells harboring NPM-ALK after 72 hrs by MTT assay, IC50 = 0.041 μM.	30223120
BAF3	Antiproliferative assay		72 hrs		Antiproliferative activity against mouse BAF3 cells harboring EML4-ALK L1196M mutant after 72 hrs by SRB or CCK8 assay, IC50 = 0.0549 μM.	29288940
Ba/F3	Function assay		72 hrs		Inhibition of EML4-ALK G1269A mutant (unknown origin) expressed in mouse Ba/F3 cells assessed as cell viability after 72 hrs by MTS assay, IC50 = 0.057 μM.	26568289
HCC78	Antiproliferative assay		72 hrs		Antiproliferative activity against human HCC78 cells harboring SLC34A2-ROS1 after 72 hrs by MTT assay, IC50 = 0.058 μM.	29174809
HCC78	Antiproliferative assay		72 hrs		Antiproliferative activity against human HCC78 cells harboring SLC34A2-ROS1 after 72 hrs by MTT assay, IC50 = 0.058 μM.	30223120
Ba/F3	Function assay		72 hrs		Inhibition of EML4-ALK L1196M mutant (unknown origin) expressed in mouse Ba/F3 cells assessed as cell viability after 72 hrs by MTS assay, IC50 = 0.064 μM.	26568289
DFCI76	Antiproliferative assay		72 hrs		Antiproliferative activity against human DFCI76 cells expressing EML4-ALK L1152R mutant after 72 hrs by CellTiter-Glo Luminescent Cell Viability Assay, EC50 = 0.072 μM.	26568289
BAF3	Antiproliferative assay				Antiproliferative activity against mouse BAF3 cells expressing ALK L1196M mutant, CC50 = 0.075 μM.	26235945
BA/F3	Function assay		72 hrs		Inhibition of ALK L1196M mutant in mouse BA/F3 cells assessed as inhibition of cell proliferation after 72 hrs by WST1 assay, CC50 = 0.075 μM.	26923695
BA/F3	Function assay		72 hrs		Inhibition of EML4 fused ALK L1196M mutant (unknown origin) expressed in mouse BA/F3 cells assessed as cell growth inhibition measured after 72 hrs by SRB assay, CC50 = 0.075 μM.	27915169
BA/F3	Function assay		72 hrs		Inhibition of EML4 fused ALK (unknown origin) expressed in mouse BA/F3 cells assessed as cell growth inhibition measured after 72 hrs by SRB assay, CC50 = 0.075 μM.	27915169
BAF3	Function assay		72 hrs		Inhibition of ALK L1196M mutant (unknown origin) expressed in mouse BAF3 cells assessed as cell growth inhibition after 72 hrs by WST-1 assay, CC50 = 0.075 μM.	28385505
KARPAS299	Antiproliferative assay		72 hrs		Antiproliferative activity against human KARPAS299 cells harboring NPM-ALK after 72 hrs by SRB or CCK8 assay, IC50 = 0.084 μM.	29288940
SMS-KCNR	Antiproliferative assay		72 hrs		Antiproliferative activity against human SMS-KCNR cells expressing EML4-ALK R1275Q mutant after 72 hrs by CellTiter-Glo Luminescent Cell Viability Assay, EC50 = 0.092 μM.	26568289
NCI-H3122	Antiproliferative assay		72 hrs		Antiproliferative activity against human NCI-H3122 cells after 72 hrs by SRB or CCK8 assay, IC50 = 0.096 μM.	29288940
NCI-H2228	Antiproliferative assay		72 hrs		Antiproliferative activity against human NCI-H2228 cells harboring EML4-ALK after 72 hrs by MTT assay, IC50 = 0.099 μM.	29174809
Ba/F3	Function assay		72 hrs		Inhibition of EML4-ALK F1174L mutant (unknown origin) expressed in mouse Ba/F3 cells assessed as cell viability after 72 hrs by MTS assay, IC50 = 0.101 μM.	26568289
NCI-H2228	Cytotoxicity assay		72 hrs		Cytotoxicity against human NCI-H2228 cells assessed as cell viability after 72 hrs by MTS assay, IC50 = 0.1026 μM.	25644671
LAN5	Antiproliferative assay		72 hrs		Antiproliferative activity against human LAN5 cells expressing EML4-ALK R1275Q mutant after 72 hrs by CellTiter-Glo Luminescent Cell Viability Assay, EC50 = 0.122 μM.	26568289
SU-DHL1	Antiproliferative assay		72 hrs		Antiproliferative activity against human SU-DHL1 cells harboring NPM-ALK after 72 hrs by SRB or CCK8 assay, IC50 = 0.122 μM.	29288940
Kelly	Antiproliferative assay		72 hrs		Antiproliferative activity against human Kelly cells expressing EML4-ALK F1174L mutant after 72 hrs by CellTiter-Glo Luminescent Cell Viability Assay, EC50 = 0.142 μM.	26568289
Ba/F3	Function assay		72 hrs		Inhibition of EML4-ALK C1156Y mutant (unknown origin) expressed in mouse Ba/F3 cells assessed as cell viability after 72 hrs by MTS assay, IC50 = 0.164 μM.	26568289
SH-SY5Y	Antiproliferative assay		72 hrs		Antiproliferative activity against human SH-SY5Y cells expressing EML4-ALK F1174L mutant after 72 hrs by CellTiter-Glo Luminescent Cell Viability Assay, EC50 = 0.186 μM.	26568289
BAF3	Antiproliferative assay		72 hrs		Antiproliferative activity against mouse BAF3 cells harboring CD74-ROS1 after 72 hrs by SRB or CCK8 assay, IC50 = 0.234 μM.	29288940
SK-N-SH	Antiproliferative assay		72 hrs		Antiproliferative activity against human SK-N-SH cells expressing EML4-ALK F1174L mutant after 72 hrs by CellTiter-Glo Luminescent Cell Viability Assay, EC50 = 0.303 μM.	26568289
BAF3	Function assay		2 to 3 days		Inhibition of TEL-fused insulin receptor (unknown origin) expressed in mouse BAF3 cells after 2 to 3 days by luciferase reporter gene assay, IC50 = 0.3195 μM.	23742252
BA/F3	Cytotoxicity assay				Cytotoxicity against mouse BA/F3 cells transfected with Tel-InsR gene assessed as growth inhibition, IC50 = 0.32 μM.	23837797
SK-N-FI	Antiproliferative assay		72 hrs		Antiproliferative activity against human SK-N-FI cells expressing wild type EML4-ALK after 72 hrs by CellTiter-Glo Luminescent Cell Viability Assay, EC50 = 0.349 μM.	26568289
CHLA20	Antiproliferative assay		72 hrs		Antiproliferative activity against human CHLA20 cells expressing EML4-ALK R1275Q mutant after 72 hrs by CellTiter-Glo Luminescent Cell Viability Assay, EC50 = 0.363 μM.	26568289
Ba/F3	Function assay		72 hrs		Inhibition of EML4-ALK G1202R mutant (unknown origin) expressed in mouse Ba/F3 cells assessed as cell viability after 72 hrs by MTS assay, IC50 = 0.444 μM.	26568289
LAN1	Antiproliferative assay		72 hrs		Antiproliferative activity against human LAN1 cells expressing EML4-ALK F1174L mutant after 72 hrs by CellTiter-Glo Luminescent Cell Viability Assay, EC50 = 0.549 μM.	26568289
SK-N-BE(2)	Antiproliferative assay		72 hrs		Antiproliferative activity against human SK-N-BE(2) cells expressing wild type EML4-ALK after 72 hrs by CellTiter-Glo Luminescent Cell Viability Assay, EC50 = 0.593 μM.	26568289
Ba/F3	Function assay		72 hrs		Inhibition of EML4-ALK 1151Tins mutant (unknown origin) expressed in mouse Ba/F3 cells assessed as cell viability after 72 hrs by MTS assay, IC50 = 0.668 μM.	26568289
BAF3	Antiproliferative assay		72 hrs		Antiproliferative activity against mouse BAF3 cells harboring EML4-ALK G1202R mutant after 72 hrs by SRB or CCK8 assay, IC50 = 0.726 μM.	29288940
Ba/F3	Function assay		72 hrs		Inhibition of human EGFR del19/T790M/C797S mutant expressed in mouse Ba/F3 cells assessed as cell growth inhibition after 72 hrs by CellTiter-Glo assay, GI50 = 0.7805 μM.	29136465
SK-N-AS	Antiproliferative assay		72 hrs		Antiproliferative activity against human SK-N-AS cells expressing wild type EML4-ALK after 72 hrs by CellTiter-Glo Luminescent Cell Viability Assay, EC50 = 1.045 μM.	26568289
BAF3	Cytotoxicity assay		2 to 3 days		Cytotoxicity against mouse BAF3 cells after 2 to 3 days by luciferase reporter gene assay, IC50 = 2.477 μM.	23742252
Ba/F3	Function assay		72 hrs		Inhibition of EML4-ALK L1152R mutant (unknown origin) expressed in mouse Ba/F3 cells assessed as cell viability after 72 hrs by MTS assay, IC50 = 2.747 μM.	26568289
BA/F3	Cytotoxicity assay		72 hrs		Cytotoxicity against mouse BA/F3 cells assessed as cell viability after 72 hrs by MTS assay, IC50 = 5.512 μM.	26568289
KARPAS299	Apoptosis assay	60 nM	24 hrs		Induction of apoptosis in human KARPAS299 cells harboring NPM-ALK at 60 nM after 24 hrs by acridine orange/ethidium bromide staining based fluorescence microscopic method	29174809
SU-DHL1	Function assay	20 to 200 nM	1 hr		Inhibition of ALK in human SU-DHL1 cells assessed as reduction in STAT3 phosphorylation at Y705 residue at 20 to 200 nM after 1 hr by Western blot analysis	29288940
SU-DHL1	Function assay	20 to 200 nM	1 hr		Inhibition of ALK phosphorylation at Y1278 residue in human SU-DHL1 cells at 20 to 200 nM after 1 hr by Western blot analysis	29288940
NCI-H3122	Function assay	20 to 200 nM	1 hr		Inhibition of ALK in human NCI-H3122 cells assessed as reduction in ERK phosphorylation at T202//Y204 residues at 20 to 200 nM after 1 hr by Western blot analysis	29288940
NCI-H3122	Function assay	20 to 200 nM	1 hr		Inhibition of ALK in human NCI-H3122 cells assessed as reduction in Akt phosphorylation at S473 residue at 20 to 200 nM after 1 hr by Western blot analysis	29288940
SU-DHL1	Function assay	20 to 200 nM	1 hr		Inhibition of ALK in human SU-DHL1 cells assessed as reduction in Akt phosphorylation at S473 residue at 20 to 200 nM after 1 hr by Western blot analysis	29288940
SU-DHL1	Function assay	20 to 200 nM	1 hr		Inhibition of ALK in human SU-DHL1 cells assessed as reduction in ERK phosphorylation at T202//Y204 residues at 20 to 200 nM after 1 hr by Western blot analysis	29288940
NCI-H3122	Function assay	20 to 200 nM	1 hr		Inhibition of ALK phosphorylation at Y1278 residue in human NCI-H3122 cells at 20 to 200 nM after 1 hr by Western blot analysis	29288940
NCI-H3122	Function assay	20 to 200 nM	1 hr		Inhibition of ALK in human NCI-H3122 cells assessed as reduction in STAT3 phosphorylation at Y705 residue at 20 to 200 nM after 1 hr by Western blot analysis	29288940
SU-DHL1	Function assay	30 nM	16 hrs		Inhibition of ALK autophosphorylation at Y1507 residue in human SU-DHL1 cells at 30 nM after 16 hrs by Western blot analysis	29627725
SU-DHL1	Function assay	30 nM	16 hrs		Inhibition of ALK in human SU-DHL1 cells assessed as reduction in STAT3 phosphorylation at Y705 residue at 30 nM after 16 hrs by Western blot analysis	29627725
NCI-H3122	Function assay	50 to 250 nM	16 hrs		Induction of ALK degradation in human NCI-H3122 cells assessed as decrease in ALK phosphorylation at Y1604 at 50 to 250 nM after 16 hrs by immunoblot method	29660984
SH-SY5Y	Antiproliferative assay		72 hrs		Antiproliferative activity against human SH-SY5Y cells after 72 hrs by CellTiter-Glo luminescent cell viability assay	29660984
CHLA20	Antiproliferative assay		72 hrs		Antiproliferative activity against human CHLA20 cells after 72 hrs by CellTiter-Glo luminescent cell viability assay	29660984
SH-SY5Y	Antiproliferative assay		72 hrs		Antiproliferative activity against human SH-SY5Y cells after 72 hrs in presence of ABCB1 inhibitor tariquidar by CellTiter-Glo luminescent cell viability assay	29660984
KARPAS299	Function assay	50 to 250 nM	16 hrs		Induction of ALK degradation in human KARPAS299 cells assessed as decrease in ALK phosphorylation at Y1604 at 50 to 250 nM after 16 hrs by immunoblot method	29660984
CHLA20	Antiproliferative assay		72 hrs		Antiproliferative activity against human CHLA20 cells after 72 hrs in presence of ABCB1 inhibitor tariquidar by CellTiter-Glo luminescent cell viability assay	29660984
NCI-H3122	Antiproliferative assay		72 hrs		Antiproliferative activity against human NCI-H3122 cells after 72 hrs by CellTiter-Glo luminescent cell viability assay	29660984
KARPAS299	Antiproliferative assay		72 hrs		Antiproliferative activity against human KARPAS299 cells after 72 hrs by CellTiter-Glo luminescent cell viability assay	29660984
SU-DHL1	Antiproliferative assay		72 hrs		Antiproliferative activity against human SU-DHL1 cells after 72 hrs by CellTiter-Glo luminescent cell viability assay	29660984
KARPAS299	Apoptosis assay	50 nM	24 hrs		Induction of apoptosis in human KARPAS299 cells assessed as unclear cell shrinkage at 50 nM after 24 hrs by Hoechst 33258 staining based inverted fluorescence microscopy	30223120
KARPAS299	Apoptosis assay	50 nM	24 hrs		Induction of apoptosis in human KARPAS299 cells assessed as late apoptotic cells at 50 nM after 24 hrs by AO/EB double staining based inverted fluorescence microscopy	30223120
KARPAS299	Apoptosis assay	50 nM	24 hrs		Induction of apoptosis in human KARPAS299 cells assessed as fragmentation at 50 nM after 24 hrs by Hoechst 33258 staining based inverted fluorescence microscopy	30223120
Klik om meer experimentele gegevens over de cellijn te bekijken

Chemische informatie, Opslag en Stabiliteit

Moleculair gewicht	558.14	Formule	C₂₈H₃₆ClN₅O₃S	Opslag (Vanaf de ontvangstdatum)	3 jaar-20°Cpoeder
CAS-nr.	1032900-25-6	SDF downloaden		Opslag van stamoplossingen	1 jaar-80°Cin oplosmiddel 1 maand-20°Cin oplosmiddel
Synoniemen	LDK378			Smiles	CC1=CC(=C(C=C1C2CCNCC2)OC(C)C)NC3=NC=C(C(=N3)NC4=CC=CC=C4S(=O)(=O)C(C)C)Cl

Oplosbaarheid

In vitro
Batch:

DMSO : 4 mg/mL (7.16 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.
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	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Gevalideerd door Selleck labs. Mocht u aanpassingen aan deze formulering nodig hebben, neem dan contact op met ons verkoopteam voor aangepaste tests.	0.150mg/ml (0.27mM)	Taking the 1 mL working solution as an example, add 50 μL 3 mg/ml clarified DMSO stock solution to 400 μL PEG300, mix evenly to clarify it; add 50 μL Tween80 to the above system, mix evenly to clarify it; then continue to add 500 μL ddH2O to adjust the volume 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	Does not cross react with c-Met, and has an improved in vivo glucose homeostasis profile relative to TAE684. May be active in Crizotinib-relapsed tumors.
Targets/IC₅₀/Ki	ALK (Cell-free assay) 0.2 nM Insulin Receptor (Cell-free assay) 7 nM IGF-1R (Cell-free assay) 8 nM STK22D (Cell-free assay) 23 nM FLT3 (Cell-free assay) 60 nM
In vitro	LDK378 vertoont een grote anti-proliferatieve activiteit in Ba/F3-NPM-ALK en Karpas290 cellen met een IC50 van 26,0 nM en 22,8 nM, vergeleken met een IC50 van 319,5 nM en 2477 nM in Ba/F3-Tel-InsR en Ba/F3-WT cellen.
Kinase Assay	Beschrijving van enzymatische kinaseprofilering
Kinase Assay	Alle kinasen worden uitgedrukt als ofwel Histidine- of GST-gelabelde fusie-eiwitten met behulp van de baculovirusexpressietechnologie, behalve de ongelabelde ERK2 die in E. coli wordt geproduceerd. De kinaseactiviteit wordt gemeten in de LabChip mobility shift assay. De assay wordt uitgevoerd bij 30°C gedurende 60 min. Het effect van deze verbinding op de enzymatische activiteit wordt verkregen uit de lineaire voortgangscurves in afwezigheid en aanwezigheid van deze verbinding en routinematig bepaald uit één meting (eindpuntmeting)
In vivo	LDK378 is ontworpen om de mogelijkheid van het vormen van reactieve metabolieten te verminderen en vertoont ondetecteerbare niveaus van glutathion (GSH) adducten (<1%) in levermicrosomen. Deze verbinding heeft een relatief goede metabole stabiliteit, met matige CYP3A4 (Midazolam substraat) remming en hERG remming. Het vertoont een lage plasma klaring bij dieren (muis, rat, hond en aap) vergeleken met de leverbloedstroom, met een orale biologische beschikbaarheid van meer dan 55% bij muis, rat, hond en aap. Het induceert een dosisafhankelijke groeiremming en tumorregressie in de Karpas299 en H2228 rat xenograft modellen, zonder gewichtsverlies. Deze chemische stof heeft geen invloed op insulineniveaus of plasma glucosegebruik bij de muis bij chronische dosering tot 100 mg/kg.
Referenties	[1] https://pubmed.ncbi.nlm.nih.gov/23742252/

Toepassingen

Methoden	Biomarkers	Afbeeldingen	PMID
Western blot	p-ALK / ALK / p-AKT / AKT / p-ERK / ERK pROS1 / ROS1 / pSTAT3 / STAT3		28425916
Growth inhibition assay	Cell viability		29067644

Informatie klinische proef

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

NCT-nummer	Rekrutering	Aandoeningen	Sponsor/Medewerkers	Startdatum	Fasen
NCT02450903	Completed	Non-Small-Cell Lung Cancer	Novartis Pharmaceuticals\|Novartis	August 21 2015	Phase 2
NCT02040870	Completed	Non-Small Cell Lung Cancer	Novartis Pharmaceuticals\|Novartis	March 7 2014	Phase 1\|Phase 2
NCT01950481	Completed	Normal Hepatic Function\|Impaired Hepatic Function	Novartis Pharmaceuticals\|Novartis	January 2014	Phase 1
NCT01772797	Completed	Anaplastic Lymphoma Kinase (ALK)\|Non-small Cell Lung Cancer	Novartis Pharmaceuticals\|Novartis	June 2013	Phase 1
NCT01685060	Completed	Non-Small Cell Lung Cancer	Novartis Pharmaceuticals\|Novartis	November 26 2012	Phase 2
NCT01634763	Completed	Tumors Characterized by Genetic Alterations in Anaplastic Lymphoma Kinase (ALK)	Novartis Pharmaceuticals\|Novartis	June 2012	Phase 1

Technische ondersteuning

Gebruiksaanwijzing

Tel: +1-832-582-8158 Ext:3

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Veelgestelde vragen

Vraag 1:
how to reconstitute it for oral administration to mice?

Antwoord:
It can be resuspended in 30% PEG400/0.5% Tween 80/5% propylene glycol and the suspension can be used for oral gavage feeding.

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