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TMZ(Temozolomide) Alkylating Agent

Name: TMZ(Temozolomide)
Brand: Selleck Chemicals
SKU: S1237
Rating: 5 (246 reviews)

Cat.nr.S1237

Temozolomide (TMZ) is een monofunctioneel SN-1 Alkylating Agent dat stikstofatomen in de DNA-ring en de extracyclische zuurstofgroep kan modificeren, chemisch wordt omgezet in MTIC en degradeert tot methyldiazoniumkation, dat methylgroepen overdraagt aan DNA bij fysiologische pH. Het is een DNA-schade-inductor in L-1210 en L-1210/BCNU cellen. Deze verbinding induceert apoptosis en vertoont antitumoractiviteit.

TMZ(Temozolomide) DNA/RNA Synthesis chemisch Chemical Structure

Chemische structuur

Molecuulgewicht: 194.15

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Kwaliteitscontrole

Batch: Zuiverheid: 99.99%

99.99

Gerelateerde doelwitten	HDAC PARP ATM/ATR DNA-PK WRN Topoisomerase PPAR Sirtuin Casein Kinase eIF
Overig DNA/RNA Synthesis Inhibitoren	CX-5461 (Pidnarulex) B02 SCR7 Favipiravir (T-705) EED226 RK-33 BMH-21 Triapine (3-AP) Carmofur YK-4-279

Celkweek, behandeling & werkzame concentratie

Cellijnen	Assaytype	Concentratie	Incubatietijd	Formulering	Activiteitsbeschrijving	PMID
Kelly	Growth Inhibition Assay		48 h		IC50=139.20 ± 5.95 μM	25960282
KellyCis83	Growth Inhibition Assay		48 h		IC50=251.00 ± 15.75 μM	25960282
SK-N-AS	Growth Inhibition Assay		48 h		IC50=227.70 ± 22.15 μM	25960282
SK-N-ASCis24	Growth Inhibition Assay		48 h		IC50=480.60 ± 101.15 μM	25960282
CHP-212	Growth Inhibition Assay		48 h		IC50=7.97 ± 0.69 μM	25960282
CHP-212Cis100	Growth Inhibition Assay		48 h		IC50=9.55 ± 0.88 μM	25960282
U87	Function Assay	100 μM	24-72 h		induces DcR1 expression	25808868
LN229	Growth Inhibition Assay	0-50 μM			IC50=16 μM	25750273
TR-LN229	Growth Inhibition Assay	0-50 μM			IC50=77 μM	25750273
U87	Apoptosis Assay	0–200 µM	24 h		enhances CQ induced apoptosis	25681668
U251MG	Apoptosis Assay	100 μM	48 h	PBS	induces apoptosis	25680464
U87MG	Apoptosis Assay	100 μM	48 h	PBS	induces apoptosis	25680464
U87	Growth Inhibition Assay	50-350 μM	48 h		inhibits cell growth slightly	25554223
U118	Growth Inhibition Assay	50-350 μM	48 h		inhibits cell growth slightly	25554223
U87	Function Assay	250/350 μM	48 h		enhances TMX-induced p-PKC-pan decrease	25554223
U118	Function Assay	250/350 μM	48 h		enhances TMX-induced p-PKC-pan decrease	25554223
U87	Growth Inhibition Assay	250/350 μM	48 h		increases the percentage of cells in S and G2/M cotreated with TMX	25554223
A375	Growth Inhibition Assay		48 h		IC50=265 μM	25524552
A2058	Growth Inhibition Assay		48 h		IC50=12 μM	25524552
M238	Growth Inhibition Assay		48 h		IC50=40 μM	25524552
M249	Growth Inhibition Assay		48 h		IC50=254 μM	25524552
M21	Growth Inhibition Assay		48 h		IC50=221 μM	25524552
U251	Cytotoxity Assay	20 μM	48 h		reduceds the percentages of colonies formed	25434381
LN229	Cytotoxity Assay	20 μM	48 h		reduceds the percentages of colonies formed	25434381
U373MG-LUC	Growth Inhibition Assay		72 h		IC50>600 μM	25431953
U87	Growth Inhibition Assay	25-200 μM	48 h		inhibits cell growth in a dose-dependent manner	25400745
U251	Growth Inhibition Assay	25-200 μM	48 h		inhibits cell growth in a dose-dependent manner	25400745
U251	Growth Inhibition Assay	100-400 μM	72/96 h		the anti-proliferative effect can be enhanced by gossypol enhanced	25375271
U373	Growth Inhibition Assay	100-400 μM	72/96 h		the anti-proliferative effect can be enhanced by gossypol enhanced	25375271
U343	Growth Inhibition Assay	100-400 μM	72/96 h		the anti-proliferative effect can be enhanced by gossypol enhanced	25375271
U87MG-luc2	Growth Inhibition Assay	100-400 μM	72/96 h		the anti-proliferative effect can be enhanced by gossypol enhanced	25375271
U87	Function Assay	200 μM	48 h		increases BRCC3 mRNA expression	25337721
U251	Function Assay	200 μM	48 h		increases BRCC3 mRNA expression	25337721
A172	Function Assay	200 μM	48 h		increases BRCC3 mRNA expression	25337721
U251	Function Assay	200 μM	48 h		increases the expression of BRCA1, BRCA2, RAD51 and FANCD2	25337721
A172	Function Assay	200 μM	48 h		increases the expression of BRCA1, BRCA2, RAD51 and FANCD2	25337721
U87	Function Assay	200 μM	24/72/120 h		increases γH2AX foci formation time-dependently	25337721
U251	Function Assay	200 μM	24/72/120 h		increases γH2AX foci formation time-dependently	25337721
A172	Function Assay	200 μM	24/72/120 h		increases γH2AX foci formation time-dependently	25337721
SNB19V	Growth Inhibition Assay		7 d	DMSO	GI50=35.7±12 μM	25277441
SNB19M	Growth Inhibition Assay		7 d	DMSO	GI50=469.9±88 μM	25277441
SNB19VR	Growth Inhibition Assay		7 d	DMSO	GI50=280.2±18 μM	25277441
U373V	Growth Inhibition Assay		7 d	DMSO	GI50=68.0±32 μM	25277441
U373M	Growth Inhibition Assay		7 d	DMSO	GI50=368.7±86 μM	25277441
U373VR	Growth Inhibition Assay		7 d	DMSO	GI50=288.8±33 μM	25277441
U87MG	Growth Inhibition Assay		7 d	DMSO	GI50=38.3±20 μM	25277441
HCT116	Growth Inhibition Assay		7 d	DMSO	GI50=579.9±32 μM	25277441
DLD1	Growth Inhibition Assay		7 d	DMSO	GI50=501.4±93 μM	25277441
MRC5	Growth Inhibition Assay		7 d	DMSO	GI50=449.4±8 μM	25277441
SNB19V	Function Assay	100 μM TMZ	0-72 h		increases γH2AX expression between 16 and 72 h	25277441
T98G	Growth Inhibition Assay	5/10/15 μM	24 h		induces cell death dose-dependently after concomitant-temozolomide with NPe6-PDT	25262961
U251	Growth Inhibition Assay	5/10/15 μM	24 h		induces cell death dose-dependently after concomitant-temozolomide with NPe6-PDT	25262961
T98G	Function Assay	15 μM	24 h		increases DNA-fragmentation in NPe6-PDT treated glioma cells	25262961
U251	Function Assay	15 μM	24 h		increases DNA-fragmentation in NPe6-PDT treated glioma cells	25262961
U-87 MG	Growth Inhibition Assay		72 h		IC50=0.93 mM	25245332
U-118 MG	Growth Inhibition Assay		72 h		IC50=1.05 mM	25245332
U87	Growth Inhibition Assay		24 h		IC50=260.34 μM	25173233
U87 GSLCs	Growth Inhibition Assay		24 h		IC50=766.11 μM	25173233
U87MG	Growth Inhibition Assay		72 h		IC50=15.625 μM	25050915
U251	Growth Inhibition Assay	100-400 μM	48 h	DMSO	inhibits cell growth in a dose-dependent manner	24623736
U87	Growth Inhibition Assay	100-400 μM	48 h	DMSO	inhibits cell growth in a dose-dependent manner	24623736
MDA-MB-231-br	Growth Inhibition Assay	0-10 μM	48 h	DMSO	inhibits cell growth in a dose-dependent manner	24623736
HCC-1937	Growth Inhibition Assay	0-300 μM	48 h	DMSO	inhibits cell growth in a dose-dependent manner	24623736
MDA-MB-231	Growth Inhibition Assay	0-40 μM	48 h	DMSO	inhibits cell growth in a dose-dependent manner	24623736
MDA-MB-468	Growth Inhibition Assay	0-500 μM	48 h	DMSO	inhibits cell growth in a dose-dependent manner	24623736
T47D	Growth Inhibition Assay	0-100 μM	48 h	DMSO	inhibits cell growth in a dose-dependent manner	24623736
MCF7	Growth Inhibition Assay	0-1000 μM	48 h	DMSO	inhibits cell growth in a dose-dependent manner	24623736
Hs683	Growth Inhibition Assay	0-1000 μM	96 h		IC50=128.9 μM	24495907
U87	Growth Inhibition Assay	0-1000 μM	96 h		IC50=18.45 μM	24495907
LNZ308	Growth Inhibition Assay	0-1000 μM	96 h		IC50=326.7 μM	24495907
U87	Apoptosis Assay	100 μM	48 h	DMSO	increases the caspase-3/7 activity	24481586
U251	Apoptosis Assay	100 μM	48 h	DMSO	increases the caspase-3/7 activity	24481586
U251	Growth Inhibition Assay		24 h		IC50=86.29 ± 1.58 μM	24326954
U251	Growth Inhibition Assay		48 h		IC50=75.34 ± 1.02 μM	24326954
U251	Growth Inhibition Assay		72 h		IC50=72.42 ± 1.45 μM	24326954
U251	Growth Inhibition Assay		96 h		IC50=69.82 ± 3.04 μM	24326954
T98G	Growth Inhibition Assay	0-750 μM	72/96 h		inhibits cell viability in a dose dependent manner	24324080
U251-MG	Growth Inhibition Assay	0-800 μM	72 h		inhibits cell viability in a dose dependent manner	24093630
D54-MG	Growth Inhibition Assay	0-800 μM	72 h		inhibits cell viability in a dose dependent manner	24093630
SHG-44	Growth Inhibition Assay	10-200 μM	96 h		IC50=9.73 ± 2.12 μM	24065569
U373	Growth Inhibition Assay	10-200 μM	96 h		IC50=10.13 ± 1.02 μM	24065569
HT-29	Function Assay	500 μM	24/48 h		enhances the levels of γ-H2AX	24038068
PC-3	Growth Inhibition Assay	0-25 μM	48 h		inhibits cell growth which can be potentiated by lycopene	23746934
PC-3	Apoptosis Assay	25 μM	48 h		induces apoptosis which can be potentiated by lycopene	23746934
T98G	Growth Inhibition Assay	50-400 μM	144 h		inhibits cell viability in a dose dependent manner	23715499
U87-MG	Growth Inhibition Assay	100 µM	72 h		inhibits cell growth which can be enhanced by GTB	23696788
U251-MG	Growth Inhibition Assay	100 µM	72 h		inhibits cell growth which can be enhanced by GTB	23696788
LNT-229	Growth Inhibition Assay	3-100 μM	24 h		inhibits clonogenic survival in a dose-dependent manner	23667632
T98G	Growth Inhibition Assay	10-700 μM	24 h		inhibits clonogenic survival in a dose-dependent manner	23667632
U87	Function Assay	100 µM	3 h		elevates the levels of pChk1 and pChk2	23667469
HCT116	Function Assay	100 µM	3 h		induces the Chk1 Phosphorylation	23667469
HCT3-6	Function Assay	100 µM	3 h		induces the Chk1 Phosphorylation	23667469
U-87	Growth Inhibition Assay	0-40 μM	12 d		inhibits cell growth in a dose-dependent manner	23645729
U-87	Apoptosis Assay	0-40 μM	3/6 d		induces apoptosis in both dose- and time-dependent manner	23645729
U-87	Function Assay	0-40 μM	3/6 d		induces autophagy in both dose- and time-dependent manner	23645729
GB-SCC010	Growth Inhibition Assay		4 d		IC50=226 μM	23612755
GB-SCC026	Growth Inhibition Assay		4 d		IC50=53.1 μM	23612755
GB-SCC028	Growth Inhibition Assay		4 d		IC50=167 μM	23612755
U87	Growth Inhibition Assay		4 d		IC50=45.2 μM	23612755
U87 stem cell	Growth Inhibition Assay		4 d		IC50=66.7 μM	23612755
TLX5 lymphoma	Cytotoxicity assay				IC50 = 5 μM	7739008
GM892 A	Cytotoxicity assay				IC50 = 7.6 μM	7739008
TLX5 lymphoma	Cytotoxicity assay				IC50 = 5 μM	12459014
HCT116	Cytotoxicity assay		4 days		IC50 = 4.34 μM	19800803
SNB75	Antiproliferative assay	10 uM	24 hrs		Antiproliferative activity against human SNB75 cells at 10 uM after 24 hrs by SRB assay	22268526
C6	Antiproliferative assay	100 uM	48 hrs		Antiproliferative activity against rat C6 cells at 100 uM after 48 hrs by neutral red incorporation assay	22268526
SF295	Antiproliferative assay	10 uM	24 hrs		Antiproliferative activity against human SF295 cells at 10 uM after 24 hrs by SRB assay	22268526
U87	Antiproliferative assay		5 days		IC50 = 49 μM	22608389
U138MG	Cytotoxicity assay		48 hrs		IC50 = 26 μM	23069682
C6	Cytotoxicity assay		48 hrs		IC50 = 34 μM	23069682
A2780	Antitumor assay		5 days		IC50 = 8.5 μM	23895620
A2058	Antitumor assay		5 days		IC50 = 35.5 μM	23895620
SNB19	Antitumor assay		5 days		IC50 = 37 μM	23895620
M8	Apoptosis assay	50 to 100 uM	48 hrs		Induction of apoptosis in human M8 cells assessed as apoptotic/necrotic cells at 50 to 100 uM after 48 hrs by APC-labeled annexin V and 7-AAD staining-based flow cytometric analysis	24125877
SK-MEL-30	Apoptosis assay	100 uM	48 hrs		Induction of apoptosis in human SK-MEL-30 cells assessed as apoptotic/necrotic cells at 100 uM after 48 hrs by APC-labeled annexin V and 7-AAD staining-based flow cytometric analysis relative to control	24125877
SK-MEL-30	Apoptosis assay	50 uM	48 hrs		Induction of apoptosis in human SK-MEL-30 cells assessed as apoptotic/necrotic cells at 50 uM after 48 hrs by APC-labeled annexin V and 7-AAD staining-based flow cytometric analysis relative to control	24125877
MNT1	Apoptosis assay	100 uM	48 hrs		Induction of apoptosis in human MNT1 cells assessed as apoptotic/necrotic cells at 100 uM after 48 hrs by APC-labeled annexin V and 7-AAD staining-based flow cytometric analysis relative to control	24125877
MNT1	Apoptosis assay	50 uM	48 hrs		Induction of apoptosis in human MNT1 cells assessed as apoptotic/necrotic cells at 50 uM after 48 hrs by APC-labeled annexin V and 7-AAD staining-based flow cytometric analysis relative to control	24125877
A2780	Cytotoxicity assay		5 days		Cytotoxicity against human A2780 cells after 5 days by MTT assay	24900418
A2780/CP70	Cytotoxicity assay		5 days		Cytotoxicity against MMR-deficient human A2780/CP70 cells after 5 days by MTT assay	24900418
GBM 047T	Antitumor assay	20 uM	1 to 2 weeks		Tumoricidal effect in patient derived GBM 047T cells assessed as reduction in neurosphere formation at 20 uM after 1 to 2 weeks by 3D tumor clonogenic assay	26355532
GBM 464T	Antitumor assay	20 uM	1 to 2 weeks		Tumoricidal effect in patient derived GBM 464T cells assessed as reduction in neurosphere formation at 20 uM after 1 to 2 weeks by 3D tumor clonogenic assay	26355532
U87MG	Function assay		3 hrs		Induction of DNA alkylation in human U87MG cells assessed as increase in N7-MedG formation after 3 hrs by LC-MS/MS analysis	27614414
U87MG	Antitumor assay				Antitumor activity against human U87MG cells orthotopically xenografted in Harlan nude mouse brain assessed as induction of slow tumor growth at 50 umol/kg, iv administered once daily for 5 days	27614414
U87MG	Antitumor assay				Antitumor activity against human U87MG cells orthotopically xenografted in Harlan nude mouse brain assessed as increase in mouse survival at 50 umol/kg, iv administered once daily for 5 days	27614414
MDCK	Cytotoxicity assay		24 hrs		Cytotoxicity against MDCK cells expressing carbonic anhydrase 9 assessed as reduction in cell viability incubated for 24 hrs measured after 7 days under normoxic condition by methylene blue staining based clonogenic survival assay	27823879
MDCK	Cytotoxicity assay		24 hrs		Cytotoxicity against MDCK cells expressing carbonic anhydrase 9 assessed as reduction in cell viability incubated for 24 hrs measured after 7 days under hypoxic condition by methylene blue staining based clonogenic survival assay	27823879
NB-EBc1	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells	29435139
C6	Cytotoxicity assay		4 days		EC50 = 16.5 μM	ChEMBL
U87	Cytotoxicity assay		72 hrs		IC50 = 19.38 μM	ChEMBL
SNB19	Growth inhibition assay		7 days		GI50 = 35.7 μM	ChEMBL
SNB19	Growth inhibition assay		7 days		GI50 = 45.6 μM	ChEMBL
U373	Function assay	100 uM	72 hrs		Induction of double stranded DNA break in empty vector transfected human U373 cells assessed as increase in gamma-H2AX level at 100 uM after 72 hrs by flow cytometry	ChEMBL
Glioma	Antitumor assay				Antitumor activity against Homo sapiens (human) Glioma cells xenografted in transgenic mouse assessed as mouse survival	ChEMBL
Klik om meer experimentele gegevens over cellijnen te bekijken

Chemische informatie, opslag en stabiliteit

Molecuulgewicht	194.15	Formule	C₆H₆N₆O₂	Opslag (vanaf de datum van ontvangst)	3 years-20°C （in the dark）powder
CAS-nr.	85622-93-1	SDF downloaden		Opslag van stamoplossingen	1 jaar-80°Cin oplosmiddel 1 maand-20°Cin oplosmiddel
Synoniemen	NSC 362856,CCRG 81045,Methazolastone			Smiles	CN1C(=O)N2C=NC(=C2N=N1)C(=O)N

Oplosbaarheid

In vitro
Batch:

DMSO : 39 mg/mL (200.87 mM) Verwarmd met een waterbad van 50°C; Geultrasoneerd;
(Met vocht verontreinigd DMSO kan de oplosbaarheid verminderen. Gebruik verse, watervrije DMSO.)

Water : 10 mg/mL (超声加热五分钟)

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.
Clear solution	5%DMSO 1 30%PEG300 2 65%ddH2O Gevalideerd door Selleck labs. Mocht u aanpassingen aan deze formulering nodig hebben, neem dan contact op met ons verkoopteam voor aangepaste tests.	2.000mg/ml (10.30mM)	Taking the 1 mL working solution as an example, add 50 μL of 40 mg/ml clarified DMSO stock solution to 300 μL of PEG 300, mix evenly to clarify it; then continue to add 650 μL of 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.
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.	2.000mg/ml (10.30mM)	Taking the 1 mL working solution as an example, add 50 μL of 40 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil Gevalideerd door Selleck labs. Mocht u aanpassingen aan deze formulering nodig hebben, neem dan contact op met ons verkoopteam voor aangepaste tests.	0.400mg/ml (2.06mM)	Taking the 1 mL working solution as an example, add 50 μL of 8 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. 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.
Clear solution	5%DMSO 1 Corn oil Gevalideerd door Selleck labs. Mocht u aanpassingen aan deze formulering nodig hebben, neem dan contact op met ons verkoopteam voor aangepaste tests.	2.000mg/ml (10.30mM)	Taking the 1 mL working solution as an example, add 50 μL of 40 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. 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.
Clear solution	5%DMSO 1 Corn oil Gevalideerd door Selleck labs. Mocht u aanpassingen aan deze formulering nodig hebben, neem dan contact op met ons verkoopteam voor aangepaste tests.	5.000mg/ml (25.75mM)	Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.

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

Kenmerken	Methazolastone is a second-generation alkylating agent.
Targets/IC₅₀/Ki	DNA replication (L-1210, L-1210/BCNU cells)
In vitro	Temozolomide (TMZ) veroorzaakt de vorming van alkalilabiele DNA-plaatsen die in vergelijkbare hoeveelheden aanwezig zijn en met een vergelijkbare snelheid worden hersteld in L-1210 en L-1210/BCNU cellijnen. In L-1210, maar niet in L-1210/BCNU, induceert deze verbinding een arrestatie van cellen in de SL-G2-M-fasen. De gevoeligheid van zowel chemo-gevoelige als resistente cellen (D54-R en U87-R) wordt significant verhoogd onder hyperoxie. Zowel het middel als hyperoxie zijn geassocieerd met verhoogde fosforylering van ERK p44/42 MAPK (Erk1/2), maar in mindere mate in D54-R cellen, wat suggereert dat Erk1/2-activiteit betrokken kan zijn bij de regulatie van hyperoxie en TMZ-gemedieerde celdood. Hyperoxie versterkt de toxiciteit in GBM-cellen door inductie van apoptosis, mogelijk via MAPK-gerelateerde routes. Het induceert in monocyten de DNA-schade responsroutes ATM-Chk2 en ATR-Chk1, wat resulteert in p53-activatie. Chronische blootstelling aan deze verbinding resulteert in verworven TMZ-resistentie en verhoogt de miR-21-expressie. Behandeling ermee triggert endoplasmatisch reticulum (ER) stress met verhoogde expressie van GADD153- en GRP78-eiwitten, en verlaagt pro-caspase 12-eiwit. Het induceert Autophagy via mitochondriale schade- en ER-stress-afhankelijke mechanismen om glioomcellen te beschermen.
In vivo	Na een dagelijkse i.p. dosis van 40 mg/kg gedurende 5 opeenvolgende dagen (dagen 1-5 na tumortransplantatie), verhoogt TMZ (Temozolomide) de levensduur met 86% in L-1210 en 22% in L-1210/BCNU. In L-1210/BCNU wordt geen effect waargenomen na 100 μM of 200 μM behandeling; slechts 400 μM van deze verbinding produceerde een accumulatie van cellen in de premitotische fase, maar veel minder dan in L-1210. In L-1210/BCNU is de maximale accumulatie van cellen in SL-G2-M, na 48-72 uur, ongeveer 30% vergeleken met 23% in onbehandelde cellen. Cellen accumuleren in SL-G2-M traden ook op wanneer L-1210 leukemie-dragende muizen i.v. werden behandeld met het middel (40 mg/kg). Een dergelijk effect wordt niet waargenomen op L-1210/BCNU-cellen van muizen die dezelfde dosis van het medicijn kregen.
Referenties	[1] https://pubmed.ncbi.nlm.nih.gov/3621181/ [2] https://pubmed.ncbi.nlm.nih.gov/22763762/ [3] https://pubmed.ncbi.nlm.nih.gov/22768182/ [4] https://pubmed.ncbi.nlm.nih.gov/22753745/ [5] https://pubmed.ncbi.nlm.nih.gov/22745676/ [6] https://pubmed.ncbi.nlm.nih.gov/22627392/

Toepassingen

Methoden	Biomarkers	PMID
Western blot	pERK / ERK / p-p38 / p38 DR5 / c-FLIP / Survivin / XIAP	24436439
Growth inhibition assay	Cell viability	25751281
Immunofluorescence	Phalloidin / Phospho-H2A.X cleaved caspase-3	27375225

Informatie over klinische proeven

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

NCT-nummer	Werving	Aandoeningen	Sponsor/medewerkers	Startdatum	Fasen
NCT05128734	Not yet recruiting	Breast Cancer Triple Negative	AHS Cancer Control Alberta	July 1 2024	Phase 2
NCT06161974	Not yet recruiting	High Grade Glioma\|Astrocytoma\|Astrocytoma Grade III\|Astrocytoma Grade IV\|Diffuse Intrinsic Pontine Glioma\|WHO Grade III Glioma\|WHO Grade IV Glioma\|Metastatic Brain Tumor\|Diffuse Midline Glioma H3 K27M-Mutant\|Thalamus Tumor\|Spinal Tumor\|IDH1 Mutation\|IDH1 R132\|IDH1 R132C\|IDH1 R132H\|IDH1 R132S\|IDH1 R132G\|IDH1 R132L\|Oligodendroglioma	Rigel Pharmaceuticals\|Nationwide Children''s Hospital	June 2024	Phase 2
NCT04967690	Not yet recruiting	Newly Diagnosed Glioblastoma	Double Bond Pharmaceutical AB	January 2024	Phase 1
NCT05698524	Recruiting	Recurrent High Grade Glioma\|Anaplastic Astrocytoma\|Anaplastic Oligodendroglioma\|Glioblastoma\|Gliosarcoma	University of Nebraska\|Xynomic Pharmaceuticals Inc.	June 26 2023	Phase 1
NCT04945148	Not yet recruiting	Glioblastoma IDH-wildtype	Hopital Foch\|National Cancer Institute France	May 2023	Phase 2

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