Home Apoptosis Antifolate remmer Pemetrexed Disodium (LY231514)

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Pemetrexed Disodium (LY231514) Antifolate

Cat.Nr.S1135

Pemetrexed disodium is een nieuwe Antifolate en antimetaboliet voor TS, DHFR en GARFT met een Ki van respectievelijk 1,3 nM, 7,2 nM en 65 nM in celvrije assays. Pemetrexed induceert autofagie en Apoptosis.
Pemetrexed Disodium (LY231514) Antifolate remmer Chemical Structure

Chemische structuur

Moleculair gewicht: 471.37

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Kwaliteitscontrole

Batch: Zuiverheid: 99.97%
99.97

Celkweek, behandeling & werkconcentratie

Cellijnen Assaytype Concentratie Incubatietijd Formulering Activiteitsbeschrijving PMID
PANC-1 Function Assay 84 μM 24 h enhances EGFR, HER3 and AKT phosphorylation levels 22977607
BXPC-3 Function Assay 39.86 μM 24 h enhances EGFR, HER3 and AKT phosphorylation levels 22977607
PANC-1 Function Assay 84 μM 24 h enhances EGFR phosphorylated levels, and the protein levels  22977607
BXPC-3 Function Assay 39.86 μM 24 h enhances EGFR phosphorylated levels, and the protein levels  22977607
BXPC-3 Function Assay 39.86 μM 24 h induces S arrest (P<0.05) and decreases the number of cells in the G2/M phase  22977607
PANC-1 Growth Inhibition Assay IC50=83.76±0.19 μM 22977607
BXPC-3 Growth Inhibition Assay IC50=39.86±1.68 μM 22977607
Jurkat Growth Inhibition Assay 48 h proportion of live cells=76.7±4.3 % 23840376
DM-3 Growth Inhibition Assay 48 h proportion of live cells=101.3±2.8 % 23840376
JL-1 Growth Inhibition Assay 48 h proportion of live cells=98.2±2.2 % 23840376
ZL-34 Growth Inhibition Assay 48 h proportion of live cells=95.7±6.5 % 23840376
STAV-FCS Growth Inhibition Assay 48 h proportion of live cells=88.1±8.9 % 23840376
M-14-K Growth Inhibition Assay 48 h proportion of live cells=81.8±12.9 % 23840376
STAV-AB Growth Inhibition Assay 48 h proportion of live cells=64.4±21.8 % 23840376
LoVo Function Assay 0.05 μM 72 h DMSO  increases the percentage of cells in the S phase  23959460
HT-29 Function Assay 0.05 μM 72 h DMSO  increases the percentage of cells in the S phase  23959460
WiDr Growth Inhibition Assay 72 h  DMSO  IC50=0.019 ± 0.002 μM 23959460
SW1116 Growth Inhibition Assay 72 h  DMSO  IC50=1.70 ± 0.03 μM 23959460
HCT116 Growth Inhibition Assay 72 h  DMSO  IC50=0.049 ± 0.013 μM 23959460
SW620 Growth Inhibition Assay 72 h  DMSO  IC50=1.09 ± 0.01 μM 23959460
LoVo Growth Inhibition Assay 72 h  DMSO  IC50=0.032 ± 0.002 μM 23959460
HT-29 Growth Inhibition Assay 72 h  DMSO  IC50=10.07 ± 0.94 μM 23959460
A549/PEM-16 Growth Inhibition Assay 96 h IC50=51.45 μM 24348854
A549/PEM-6.4 Growth Inhibition Assay 96 h IC50=23.39 μM 24348854
A549/PEM-1.6 Growth Inhibition Assay 96 h IC50=5.03 μM 24348854
A549 Growth Inhibition Assay 96 h IC50=1.35 μM 24348854
MSTO-211H Cell Viability Assay 1-10 μg/ml 72 h IC50~0.04 μg/ml 24378576
Y-meso14 Cell Viability Assay 1-10 μg/ml 72 h IC50>10 μg/ml 24378576
H290 Cell Viability Assay 1-10 μg/ml 72 h IC50>10 μg/ml 24378576
H226 Cell Viability Assay 1-10 μg/ml 72 h IC50>10 μg/ml 24378576
H1299 Growth Inhibition Assay IC50=1.84 μM 24418519
H1993 Growth Inhibition Assay IC50=0.17 μM 24418519
A549 Function Assay 0.1/0.3/0.5/1 μM 24/48 h DMSO produces the formation of AVOs in a dose-dependent manner 24626722
A549 Cell Viability Assay 0.1/0.3/0.5/1 μM 24/48 h DMSO inhibits cell viability dose and time dependently 24626722
MES04 Growth Inhibition Assay IC50＞100 μM 24714722
MES01 Growth Inhibition Assay IC50＞100 μM 24714722
H2452 Growth Inhibition Assay IC50＞100 μM 24714722
H2052 Growth Inhibition Assay IC50=0.57±0.34 μM 24714722
211H Growth Inhibition Assay IC50=0.07±0.01 μM 24714722
H28 Growth Inhibition Assay IC50=0.07±0.02 μM 24714722
PC9/GR Function Assay 4.94 μM 72 h increases p-AKT levels 24840891
PC9/GR Function Assay 4.94 μM 72 h increases p-ERK levels 24840891
PC9/GR Apoptosis Assay 4.94 μM 72 h induces 19.54﹪ apoptosis 24840891
PC9 Apoptosis Assay 16 nM 72 h induces 14.54﹪ apoptosis 24840891
PC9/GR Function Assay 4.94 μM 72 h induces S-phase arrest 24840891
PC9 Function Assay 16 nM 72 h induces S-phase arrest 24840891
PC9/GR Growth Inhibition Assay 72 h IC50=4.94±0.440 μM 24840891
PC9 Growth Inhibition Assay 72 h IC50=16.05±1.85 nM 24840891
A549 Function Assay 0.1/0.3/1 μM 48 h increases the ratio of S-phase population 24847863
A549 Apoptosis Assay 0.1/0.3/1 μM 48 h induces apoptosis in a dose dependent manner 24847863
A549 Function Assay 0.1/0.3/1 μM 48 h increases the level of phosphorylated Akt in a dose dependent manner 24847863
A549 Function Assay 1 µM 4/8/12/24/48 h increases the level of phosphorylated Akt in a time dependent manner 24847863
A549 Function Assay 5 μM 8 h increases Mcl-1 ubiquitination levels 24991768
A549 Apoptosis Assay 2.5 μM 48 h induces apoptosis 24991768
H1792 Function Assay 2.5/5/10 μM 48 h downregulates Mcl-1  24991768
A549  Function Assay 2.5/5/10 μM 48 h downregulates Mcl-1  24991768
H1792 Function Assay 2.5 μM 48 h induces caspase-9, caspase-3 and poly (ADP-ribose) polymerase (PARP) cleavage 24991768
A549  Function Assay 2.5 μM 48 h induces caspase-9, caspase-3 and poly (ADP-ribose) polymerase (PARP) cleavage 24991768
H1792 Function Assay 2.5/5/10 μM 48 h increases Noxa expression significantly 24991768
A549  Function Assay 2.5/5/10 μM 48 h increases Noxa expression significantly 24991768
A549 Function Assay 1 μM 48 h leads to mitochondrial dysfunction combined with simvastatin 25096993
MSTO-211 Function Assay 1 μM 48 h leads to mitochondrial dysfunction combined with simvastatin 25096993
A549 Function Assay 1 μM 48 h enhances intracellular ROS production combined with simvastatin 25096993
MSTO-211 Function Assay 1 μM 48 h enhances intracellular ROS production combined with simvastatin 25096993
A549 Apoptosis Assay 1 μM 48 h enhances caspase-dependent apoptosis combined with simvastatin 25096993
MSTO-211 Apoptosis Assay 1 μM 48 h enhances caspase-dependent apoptosis combined with simvastatin 25096993
A549 Cell Viability Assay 1 μM 48 h produces a synergistic inhibitory effect on the cell growth combined with simvastatin 25096993
MSTO-211 Cell Viability Assay 1 μM 48 h produces a synergistic inhibitory effect on the cell growth combined with simvastatin 25096993
H1299 Cell Viability Assay 1-1000 nM 72 h IC50=178 nM 25145669
A549 Cell Viability Assay 1-1000 nM 72 h IC50=137 nM 25145669
MG-63 Cell Viability Assay 0.01-100 μM 72 h inhibits cell viability dosedependently 25152399
U20S Cell Viability Assay 0.01-100 μM 72 h inhibits cell viability dosedependently 25152399
HepG3 Function Assay 10 μM 48 h upregulates phosphorylated (p-) MEK1/2 (Ser217/221) and p-ERK1/2 (Thr202/Tyr204) 25446102
HepG3 Function Assay 0.1–100 μM 48 h activates cyto-protective autophagy  25446102
HepG3 Function Assay 0.1–100 μM 48 h induces p62 downregulation as well as Beclin-1 and LC3B-II upregulation 25446102
HepG2 Apoptosis Assay 0.1–100 μM 72 h induces apoptosis slightly at high concerntration 25446102
HepG2 Cell Viability Assay 0.1–100 μM 72 h high concentrations of pemetrexed at (10/100 μM) only slightly inhibits HepG2 cell survival 25446102
A459 Apoptosis Assay 4μM 48 h induces apoptosis 25743822
A459 Function Assay 1/2/4 μM 48 h decreases the levels of p-Akt 25743822
A459 Function Assay 1/2/4 μM 24/48 h induces G1 phase arrest in dose- and time dependent manner 25743822
T47D Growth Inhibition Assay 0.234 mM 72 h growth inhibition=30﹪ 25975637
HeLa Growth Inhibition Assay 0.234 mM 72 h growth inhibition=20﹪ 25975637
A549 Growth Inhibition Assay 0.234 mM 72 h growth inhibition=50﹪ 25975637
Vero Growth Inhibition Assay 0.234 mM 72 h growth inhibition=20﹪ 25975637
T47D Growth Inhibition Assay 0.234 mM 48 h growth inhibition=20﹪ 25975637
HeLa Growth Inhibition Assay 0.234 mM 48 h growth inhibition=10﹪ 25975637
A549 Growth Inhibition Assay 0.234 mM 48 h growth inhibition=30﹪ 25975637
Vero Growth Inhibition Assay 0.234 mM 48 h growth inhibition=10﹪ 25975637
T47D Growth Inhibition Assay 0.234 mM 24 h growth inhibition=10﹪ 25975637
HeLa Growth Inhibition Assay 0.234 mM 24 h growth inhibition=5﹪ 25975637
A549 Growth Inhibition Assay 0.234 mM 24 h growth inhibition=10﹪ 25975637
Vero Growth Inhibition Assay 0.234 mM 24 h growth inhibition=5﹪ 25975637
A549 Function Assay 1 μM 48 h increases AMPK phosphorylation and a concomitant decrease in AKT and mTOR phosphorylation cotreated with simvastatin 26334320
MSTO-211H Function Assay 1 μM 48 h increases AMPK phosphorylation and a concomitant decrease in AKT and mTOR phosphorylation cotreated with simvastatin 26334320
A549 Apoptosis Assay 1 μM 24 h induces apoptosis cotreated with simvastatin 26334320
MSTO-211H Apoptosis Assay 1 μM 24 h induces apoptosis cotreated with simvastatin 26334320
A549 Function Assay 1 μM 24 h enhances autophagy cotreated with simvastatin 26334320
MSTO-211H Function Assay 1 μM 24 h enhances autophagy cotreated with simvastatin 26334320
A549 Cell Viability Assay 1 μM 48 h enhances simvastatin inhibited viability 26334320
MSTO-211H Cell Viability Assay 1 μM 48 h enhances simvastatin inhibited viability 26334320
KB Function assay IC50 = 0.03 μM 18680275
RT16 Antiproliferative assay IC50 = 0.042 μM 18680275
D4 Antiproliferative assay IC50 = 0.06 μM 18680275
KB Antiproliferative assay IC50 = 0.068 μM 18680275
IGROV1 Antiproliferative assay IC50 = 0.102 μM 18680275
PC43-10 Antiproliferative assay IC50 = 0.138 μM 18680275
IGROV1 Antiproliferative assay IC50 = 0.2 μM 18680275
D4 Antiproliferative assay IC50 = 0.254 μM 18680275
KB Antiproliferative assay IC50 = 0.327 μM 18680275
RT16 Antiproliferative assay IC50 = 0.388 μM 18680275
R2 Antiproliferative assay IC50 = 0.894 μM 18680275
KB Function assay 30 mins IC50 = 0.03 μM 19371039
R2 Function assay Ki = 0.096 μM 20085328
R2 Function assay Ki = 1.54 μM 20085328
KB Function assay IC50 = 30 μM 20085328
R2 Antiproliferative assay 10 to 14 days IC50 = 0.00494 μM 21879757
R2 Antiproliferative assay 96 hrs IC50 = 0.0132 μM 21879757
RT16 Antiproliferative assay 96 hrs IC50 = 0.042 μM 21879757
D4 Antiproliferative assay 96 hrs IC50 = 0.06 μM 21879757
KB Antiproliferative assay 96 hrs IC50 = 0.068 μM 21879757
IGROV1 Antiproliferative assay 96 hrs IC50 = 0.102 μM 21879757
PC43-10 Antiproliferative assay 96 hrs IC50 = 0.138 μM 21879757
IGROV1 Antiproliferative assay 96 hrs IC50 = 0.2 μM 21879757
D4 Antiproliferative assay 96 hrs IC50 = 0.254 μM 21879757
KB Antiproliferative assay 96 hrs IC50 = 0.327 μM 21879757
RT16 Antiproliferative assay 96 hrs IC50 = 0.388 μM 21879757
R2 Antiproliferative assay 96 hrs IC50 = 0.894 μM 21879757
R2(VC) Antiproliferative assay 96 hrs IC50 = 0.974 μM 21879757
R2 Function assay Ki = 0.094 μM 22243528
R2 Function assay Ki = 2.54 μM 22243528
R2 Growth inhibition assay 96 hrs IC50 = 0.0132 μM 24111942
RT16 Growth inhibition assay 96 hrs IC50 = 0.042 μM 24111942
D4 Growth inhibition assay 96 hrs IC50 = 0.06 μM 24111942
KB Growth inhibition assay 96 hrs IC50 = 0.068 μM 24111942
PC43-10 Growth inhibition assay 96 hrs IC50 = 0.138 μM 24111942
D4 Growth inhibition assay 96 hrs IC50 = 0.254 μM 24111942
KB Growth inhibition assay 96 hrs IC50 = 0.327 μM 24111942
RT16 Growth inhibition assay 96 hrs IC50 = 0.388 μM 24111942
MTXRII-OuaR2-4 Growth inhibition assay 96 hrs IC50 = 0.894 μM 24111942
R2(VC) Growth inhibition assay 96 hrs IC50 = 0.974 μM 24111942
KB Cytotoxicity assay 96 hrs IC50 = 0.00994 μM 24256410
KB Function assay 30 mins IC50 = 0.01174 μM 24256410
RT16 Cytotoxicity assay 96 hrs IC50 = 0.0182 μM 24256410
R2 Cytotoxicity assay 96 hrs IC50 = 0.0223 μM 24256410
PC43-10 Cytotoxicity assay 96 hrs IC50 = 0.0306 μM 24256410
KB Cytotoxicity assay 96 hrs IC50 = 0.69 μM 24256410
R2/PCFT4 Function assay 96 hrs IC50 = 0.0132 μM 25234128
RT16 Function assay 96 hrs IC50 = 0.042 μM 25234128
D4 Function assay 96 hrs IC50 = 0.06 μM 25234128
KB Cytotoxicity assay 96 hrs IC50 = 0.068 μM 25234128
PC43-10 Function assay 96 hrs IC50 = 0.138 μM 25234128
D4 Function assay 96 hrs IC50 = 0.254 μM 25234128
KB Cytotoxicity assay 96 hrs IC50 = 0.327 μM 25234128
RT16 Function assay 96 hrs IC50 = 0.388 μM 25234128
R2 Cytotoxicity assay 96 hrs IC50 = 0.894 μM 25234128
R2 Cytotoxicity assay 96 hrs IC50 = 0.974 μM 25234128
KB Function assay 1 hr IC50 = 0.01174 μM 25602637
R2/PCFT4 Function assay 96 hrs IC50 = 0.0132 μM 25602637
RT16 Function assay 96 hrs IC50 = 0.042 μM 25602637
R2 Cytotoxicity assay 96 hrs IC50 = 0.042 μM 25602637
KB Antiproliferative assay 96 hrs IC50 = 0.068 μM 25602637
PC43-10 Function assay 96 hrs IC50 = 0.138 μM 25602637
R2(VC) Cytotoxicity assay 96 hrs IC50 = 0.974 μM 25602637
KB Cytotoxicity assay 72 hrs IC50 = 0.07 μM 25668494
A549 Cytotoxicity assay 72 hrs IC50 = 0.08 μM 25668494
HepG2 Cytotoxicity assay 72 hrs IC50 = 1.26 μM 25668494
R2/PCFT4 Function assay 2 mins K = 0.044 μM 26317331
R2/PCFT4 Function assay 2 mins K = 0.27 μM 26317331
KB Antiproliferative assay 72 hrs IC50 = 0.07 μM 27017552
SW620 Antiproliferative assay 72 hrs IC50 = 0.08 μM 27017552
A549 Antiproliferative assay 72 hrs IC50 = 1.26 μM 27017552
KB Function assay 72 hrs IC50 = 0.07 μM 28830032
SW620 Antiproliferative assay 72 hrs IC50 = 0.09 μM 28830032
MCF7 Antiproliferative assay 72 hrs IC50 = 0.65 μM 28830032
R2/PCFT4 Function assay 96 hrs IC50 = 0.0132 μM 29425443
RT16 Function assay 96 hrs IC50 = 0.042 μM 29425443
D4 Function assay 96 hrs IC50 = 0.06 μM 29425443
KB Antiproliferative assay 96 hrs IC50 = 0.068 μM 29425443
PC43-10 Function assay 96 hrs IC50 = 0.138 μM 29425443
D4 Function assay 96 hrs IC50 = 0.254 μM 29425443
R2/PCFT4 Function assay 2 mins Ki = 0.259 μM 29425443
KB Antiproliferative assay 96 hrs IC50 = 0.327 μM 29425443
R2 Cytotoxicity assay 96 hrs IC50 = 0.849 μM 29425443
RT16 Function assay 96 hrs IC50 = 0.894 μM 29425443
R2(VC) Growth inhibition assay 96 hrs IC50 = 0.974 μM 29425443
A549 Antiproliferative assay 24 hrs IC50 = 3.31 μM 29807332
MDA-MB-231 Antiproliferative assay 24 hrs IC50 = 3.85 μM 29807332
OVCAR3 Antiproliferative assay 24 hrs IC50 = 6.9 μM 29807332
SGC7901 Antiproliferative assay 24 hrs IC50 = 9.08 μM 29807332
KB Function assay 1 uM 24 hrs Induction of apoptotic activity in human KB cells at 1 uM after 24 hrs 18680275
R2 Antiproliferative assay Antiproliferative activity against chinese hamster R2 cells expressing human PCFT assessed as growth inhibition in the presence of 10 uM thymidine and 320 uM AICA 21879757
R2 Antiproliferative assay Antiproliferative activity against chinese hamster R2 cells expressing human PCFT assessed as growth inhibition in the presence of 60 uM adenosine 21879757
R2 Function assay Inhibition of GARFTase in chinese hamster R2 cells expressing human PCFT assessed as incorporation of [14C]glycine into [14C]formyl GAR in the presence of 4 uM azaserine 21879757
R2 Function assay 10 uM Inhibition of human PCFT-mediated [3H]MTX uptake ectopically expressed in chinese hamster R2 cells at 10 uM at pH 5.5 to 7.2 21879757
PC43-10 Function assay 10 uM 2 mins Inhibition of human RFC-mediated [3H]MTX uptake in chinese hamster PC43-10 cells at 10 uM after 2 mins relative to control 21879757
KB Function assay 1 uM 48 hrs Inhibition of AICARFTase in human KB cells assessed as phosphorylated AMPK at 1 uM after 48 hrs by Western blot analysis 24256410
KB Cytotoxicity assay 96 hrs Cytotoxicity against human KB cells expressing human RFC/FRalpha/PCFT after 96 hrs by CellTitre-Blue fluorescence assay in presence of adenosine/AICA/thymidine 24256410
KB Cell cycle arrest assay 1 uM 48 hrs Cell cycle arrest in human KB cells assessed as accumulation at G1/G0 phase at 1 uM after 48 hrs by propidium iodide staining-based flow cytometry relative to control 24256410
KB Function assay 48 hrs Inhibition of AICARFTase in human KB cells assessed as accumulation of ZMP after 48 hrs by HPLC analysis 24256410
R2/PCFT4 Function assay 0.5 uM 5 mins Binding affinity to human PCFT expressed in Chinese hamster R2/PCFT4 cells assessed as intracellular drug level at 0.5 uM at 37 degC at pH 5.5 measured over 5 mins 26317331
TC32 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 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
NB-EBc1 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells 29435139
NB1643 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB1643 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
IGROV1 Function assay Effect on TS protein expression in human IGROV1 cells by Western blot analysis 30035541
IGROV1 Function assay Effect on DHFR protein expression in human IGROV1 cells by Western blot analysis 30035541
IGROV1 Function assay Effect on HSP90 protein expression in human IGROV1 cells by Western blot analysis 30035541
Klik om meer experimentele gegevens over de cellijn te bekijken

Chemische informatie, Opslag en Stabiliteit

Moleculair gewicht 471.37 Formule

C20H19N5Na2O6

 Opslag (Vanaf de ontvangstdatum)
CAS-nr. 150399-23-8 SDF downloaden Opslag van stamoplossingen

Synoniemen LY-231514 disodium Smiles C1=CC(=CC=C1CCC2=CNC3=C2C(=O)NC(=N3)N)C(=O)NC(CCC(=O)[O-])C(=O)[O-].[Na+].[Na+]

Oplosbaarheid

In vitro
Batch:

Water : 94 mg/mL

DMSO : Insoluble
(Met vocht verontreinigde DMSO kan de oplosbaarheid verminderen. Gebruik verse, watervrije DMSO.)

Ethanol : Insoluble

Molariteitscalculator

Massa Concentratie Volume Moleculair gewicht
Verdunningscalculator Moleculair gewicht calculator

In vivo
Batch:

In vivo Formuleringscalculator (Heldere oplossing)

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

mg/kg g μL

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

Targets/IC50/Ki
TS
(Cell-free assay)
1.3 nM(Ki)
DHFR
(Cell-free assay)
7.2 nM(Ki)
GARFT
(Cell-free assay)
65 nM(Ki)
In vitro
Pemetrexed disodium vertoont antiproliferatieve activiteit in CCRF-CEM leukemie-, GC3/C1 coloncarcinoom- en HCT-8 ileocaecaalcarcinoomcellen met een IC50 van respectievelijk 25 nM, 34 nM en 220 nM. Een recente studie toont aan dat cisplatine plus deze verbinding in combinatie met SOCS-1 genoverdracht het antitumorale effect vertoont door remming van celproliferatie, invasiviteit en inductie van apoptosis in MPM-cellen geïnfecteerd met adeno-virus-expresserend SOCS-1 vector.
Kinase Assay
Enzymtesten en -methoden.
TS-activiteit wordt getest met een spectrofotometrische methode, waarbij de toename in absorptie bij 340 nm wordt gevolgd als gevolg van de vorming van het product, 7,8-dihydrofolaat. De assaybuffer bevat 50 mM N-tris[hydroxymethyljmethyl-2-aminoethaansulfonzuur, 25 mM MgCl2, 6,5 mM formaldehyde, 1 mM EDTA en 75 mM 2-mercaptoethanol, pH 7,4. De concentraties van deoxyuridylaatmonofosfaat, 6R-MTHF en hIS zijn respectievelijk 100 μM, 30 μM en 30 nM (1,7 milli-eenheden/mL). Bij de 6R-MTHF-concentratie worden een ongeremde reactie en zes concentraties remmer getest. Ki app-waarden worden bepaald door de gegevens aan de Morrison-vergelijking aan te passen met behulp van niet-lineaire regressieanalyse met behulp van het programma ENZFITTER. Ki-waarden worden berekend met behulp van de vergelijking: Ki app = Ki(1 + [S]/Km), waarbij [S] gelijk is aan 30 μM en Km gelijk is aan 3 μM. DHFR-activiteit wordt spectrofotometrisch getest door het verdwijnen van de substraten NADPH en 7,8-dihydrofolaat bij 340 nm te volgen. De reactie vindt plaats bij 25°C in 0,5 mL 50 mM kaliumfosfaatbuffer, die 150 mM KCl en 10 nM 2-mercaptoethanol, pH 7,5, en 14 nM (0,34 milli-eenheid/mL) DHFR bevat. De NADPH-concentratie is 10 μM en 7,8-dihydrofolaat varieert bij 5, 10 of 15 μM. Bij elke 7,8-dihydrofolaatconcentratie worden een ongeremde reactie en zeven concentraties remmer getest. Het ENZFITI'ER microcomputerprogramma wordt gebruikt om Ki app-waarden te verkrijgen door de gegevens aan de Morrison-vergelijking aan te passen met niet-lineaire regressieanalyse. Ki app = Ki(1 + [S]/Km), waarbij [S] gelijk is aan de gebruikte concentratie van 7,8-dihydrofolaat en Km van 7,8-dihydrofolaat gelijk is aan 0,15 μM. GARFT-activiteit wordt spectrofotometrisch getest door de toename van de absorptie als gevolg van de vorming van het product 5,8-dideazafolaat bij 295 nm te volgen. Het reactieoplosmiddel bevat 75 mM HEPES, 20% glycerol en 50 mM a-thioglycerol, pH 7,5, bij 25°C. De concentraties van substraten en enzym gebruikt zijn 10 μM α,β-glycinamideribonucleotide, 0-10 μM 10-formyl-5,8-dideazafolic acid en 10 nM (1,9 milli-eenheden/mL) GARFT. Ki-waarden worden berekend met behulp van het Enzyme Mechanism-programma van de Beckman DU640 spectrofotometer, dat niet-lineaire regressieanalyse gebruikt om gegevens aan de Michaelis-Menten-vergelijking voor competitieve remming aan te passen.
In vivo
In het humane H460 niet-kleincellige longcarcinoom-xenograft veroorzaakt Pemetrexed disodium een duurafhankelijke vertraging van de tumorgroei (TGD).
Referenties

Toepassingen

Methoden Biomarkers Afbeeldingen PMID
Western blot EGFR / p-EGFR AKT / p-AKT / GSK3β / p-GSK3β Topo IIα / Topo I / γH2AX / Cleaved PARP / Survivin p-Chk1 / Chk1 / Cyclin D / Cyclin E / p-Histone H3 / Histone H3 / Cyclin B1 / p-Cdc2 / Cdc2
S1135-WB4
30953548
Immunofluorescence p-AKT
S1135-IF1
24847863
Growth inhibition assay Cell viability
S1135-viability1
28719077

Informatie klinische proef

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

NCT-nummer Rekrutering Aandoeningen Sponsor/Medewerkers Startdatum Fasen
NCT06378892 Recruiting
Non Small Cell Lung Cancer Metastatic|ALK Gene Mutation
Centro di Riferimento Oncologico - Aviano
 March 15 2024 Phase 2
NCT06010277 Recruiting
NSCLC|Mesothelioma|Thymoma
Amphia Hospital|Albert Schweitzer Hospital
 February 6 2023 Phase 4

Technische ondersteuning

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