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Pemetrexed Disodium (LY231514) Antifolate

Name: Pemetrexed Disodium (LY231514)
Brand: Selleck Chemicals
SKU: S1135
Rating: 5 (47 reviews)

N. Cat.: S1135

Pemetrexed disodium is a novel antifolate and antimetabolite for TS, DHFR and GARFT with K_i of 1.3 nM, 7.2 nM and 65 nM in cell-free assays, respectively. Pemetrexed induces autophagy and apoptosis.

Pemetrexed Disodium (LY231514) Antifolate inhibitor Chemical Structure

Struttura chimica

Peso molecolare: 471.37

Vai a

Controllo Qualità (Quality Control)

Lotto: Purezza: 99.97%

99.97

Target correlati	Bcl-2 Caspase PD-1/PD-L1 Ferroptosis p53 Apoptosis related Synthetic Lethality STAT TNF-alpha Ras
Altro Antifolate Inibitori	L-5-Methyltetrahydrofolate calcium

Coltura cellulare, trattamento e concentrazione di lavoro
(Cell Culture, Treatment & Working Concentration)

Linee cellulari	Tipo di saggio	Concentrazione	Tempo di incubazione	Formulazione	Descrizione dell'attività	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
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Informazioni chimiche, conservazione e stabilità (Chemical Information, Storage & Stability)

Peso molecolare	471.37	Formula	C₂₀H₁₉N₅Na₂O₆	Conservazione (Dalla data di ricezione)	3 anni-20°Cpolvere
N. CAS	150399-23-8	Scarica SDF		Conservazione delle soluzioni stock	1 anno-80°Cin solvente 1 mese-20°Cin solvente
Sinonimi	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+]

Solubilità (Solubility)

In vitro
Lotto:

Water : 94 mg/mL

DMSO : Insoluble
(Il DMSO contaminato da umidità può ridurre la solubilità. Utilizzare DMSO fresco e anidro.)

Ethanol : Insoluble

Calcolatore di Molarità

Massa	Concentrazione	Volume	Peso molecolare
=	×	×

Calcolatore di Diluizione Calcolatore del Peso Molecolare

In vivo Lotto:
Clear solution	Saline Validato dai laboratori Selleck. Se necessiti di modifiche a questa formulazione, contatta il nostro team di vendita per test personalizzati.	30.000mg/ml (63.64mM)	Taking the 1 mL working solution as an example, add 30 mg of this product to 1 ml of physiological saline (0.9% NaCL solution), mix evenly to make it clear, The mixed solution should be used immediately for optimal results.

Calcolatore di formulazione in vivo (Soluzione chiara)

Passo 1: Inserire le informazioni di seguito (Consigliato: Un animale aggiuntivo per tenere conto della perdita durante l'esperimento)

Dosaggio: mg/kg Peso medio degli animali: g Volume di dosaggio per animale:μL Numero di animali:

Passo 2: Inserire la formulazione in vivo (Questo è solo il calcolatore, non la formulazione. Contattateci prima se non c'è una formulazione in vivo nella sezione Solubilità.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Risultati del calcolo:

Concentrazione di lavoro: mg/ml;

Metodo per preparare il liquido master di DMSO: mg farmaco predissolto in μL DMSO ( Concentrazione del liquido master mg/mL, Vi preghiamo di contattarci prima se la concentrazione supera la solubilità del DMSO del lotto del farmaco. )

Metodo per preparare la formulazione in vivo: Prendere μL DMSO liquido master, quindi aggiungereμL PEG300, mescolare e chiarire, quindi aggiungereμL Tween 80, mescolare e chiarire, quindi aggiungere μL ddH₂O, mescolare e chiarire.

Metodo per preparare la formulazione in vivo: Prendere μL DMSO liquido master, quindi aggiungere μL Olio di mais, mescolare e chiarire.

Nota: 1. Si prega di assicurarsi che il liquido sia limpido prima di aggiungere il solvente successivo.
2. Assicurarsi di aggiungere il/i solvente/i in ordine. È necessario assicurarsi che la soluzione ottenuta, nell'aggiunta precedente, sia una soluzione limpida prima di procedere all'aggiunta del solvente successivo. Metodi fisici come il vortex, gli ultrasuoni o il bagno d'acqua calda possono essere utilizzati per facilitare la dissoluzione.

Meccanismo d'azione (Mechanism of Action)

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 mostra attività antiproliferativa in cellule di leucemia CCRF-CEM, carcinoma del colon GC3/C1 e carcinoma ileocecale HCT-8 con IC50 rispettivamente di 25 nM, 34 nM e 220 nM. Uno studio recente mostra che il cisplatino più questo composto combinato con la somministrazione del gene SOCS-1 mostra un effetto antitumorale attraverso l'inibizione della proliferazione cellulare, dell'invasività e l'induzione dell'apoptosi nelle cellule MPM infettate da un vettore adenovirale che esprime SOCS-1.
Saggio chinasico	Saggi e metodi enzimatici.
Saggio chinasico	L'attività della TS viene saggiata utilizzando un metodo spettrofotometrico, che comporta il monitoraggio dell'aumento di assorbanza a 340 nm risultante dalla formazione del prodotto, 7,8-diidrofolato. Il tampone del saggio contiene 50 mM di acido N-tris[idrossimetil]metil-2-amminoetansolfonico, 25 mM di MgC1₂, 6,5 mM di formaldeide, 1 mM di EDTA e 75 mM di 2-mercaptoetanolo, pH 7,4. Le concentrazioni di desossiuridilato monofosfato, 6R-MTHF e hIS sono rispettivamente 100 μM, 30 μM e 30 nM (1,7 milliunità/mL). Alla concentrazione di 6R-MTHF, vengono saggiate una reazione non inibita e sei concentrazioni di inibitore. I valori di K_{i app} vengono determinati adattando i dati all'equazione di Morrison utilizzando l'analisi di regressione non lineare con l'ausilio del programma ENZFITTER. I valori di K_i vengono calcolati utilizzando l'equazione: K_{i app}= K_i(1 + [S]/K_m), dove [S] è uguale a 30 μM e K_m è uguale a 3 μM. L'attività della DHFR viene saggiata spettrofotometricamente monitorando la scomparsa dei substrati NADPH e 7,8-diidrofolato a 340 nm. La reazione avviene a 25°C in 0,5 mL di tampone fosfato di potassio 50 mM, che contiene 150 mM di KC1 e 10 nM di 2-mercaptoetanolo, pH 7,5, e 14 nM (0,34 milliunità/mL) di DHFR. La concentrazione di NADPH è 10 μM e il 7,8-diidrofolato viene variato a 5, 10 o 15 μM. A ogni concentrazione di 7,8-diidrofolato, vengono saggiate una reazione non inibita e sette concentrazioni di inibitore. Il programma di microcomputer ENZFITI'ER viene utilizzato per ottenere i valori di K_{i app} adattando i dati all'equazione di Morrison mediante analisi di regressione non lineare. K_{i app}= K_i(1 + [S]/K_m), dove [S] è uguale alla concentrazione di 7,8-diidrofolato utilizzata e K_m di 7,8-diidrofolato è uguale a 0,15 μM. L'attività della GARFT viene saggiata spettrofotometricamente monitorando l'aumento dell'assorbanza risultante dalla formazione del prodotto 5,8-dideazafolato a 295 nm. Il solvente di reazione contiene 75 mM di HEPES, 20% di glicerolo e 50 mM di α-tioglicerolo, pH 7,5, a 25°C. Le concentrazioni dei substrati e dell'enzima utilizzati sono 10 μM di α,β-glicinamide ribonucleotide, 0-10 μM di acido 10-formil-5,8-dideazafolico e 10 nM (1,9 milliunità/mL) di GARFT. I valori di K_i vengono calcolati utilizzando il programma Enzyme Mechanism dello spettrofotometro Beckman DU640, che utilizza l'analisi di regressione non lineare per adattare i dati all'equazione di Michaelis-Menten per l'inibizione competitiva.
In vivo	Nell'xenotrapianto di carcinoma polmonare non a piccole cellule H460 umano, Pemetrexed disodium produce un ritardo della crescita tumorale (TGD) dipendente dalla durata.
Riferimenti	[1] https://pubmed.ncbi.nlm.nih.gov/9067281/ [2] https://pubmed.ncbi.nlm.nih.gov/22532243/ [3] https://pubmed.ncbi.nlm.nih.gov/10741729/

Applicazioni (Applications)

Metodi	Biomarcatori	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	30953548
Immunofluorescence	p-AKT	24847863
Growth inhibition assay	Cell viability	28719077

Informazioni sullo studio clinico (Clinical Trial Information)

(dati da https://clinicaltrials.gov, aggiornato il 2024-05-22)

Numero NCT	Reclutamento	Condizioni	Sponsor/Collaboratori	Data di inizio	Fasi
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

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