Name: Letrozole
Brand: Selleck Chemicals
SKU: S1235
Rating: 5 (39 reviews)

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Kwaliteitscontrole (Quality Control)

Batch: Zuiverheid: 99.99%

99.99

Gerelateerde doelwitten	Adrenergic Receptor Estrogen/progestogen Receptor GPR Androgen Receptor Glucocorticoid Receptor ACE RAAS Progesterone Receptor Opioid Receptor THR
Overig Aromatase Inhibitoren	Obacunone (AI3-37934) Fadrozole (CGS16949A) alpha-Naphthoflavone

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

Cellijnen	Assaytype	Concentratie	Incubatietijd	Activiteitsbeschrijving	PMID
JEG3	Function assay			Inhibition of aromatase activity in human JEG3 cells, IC50=0.00089μM	18590272
JEG3	Function assay			Inhibition of aromatase in human JEG3 cells by scintillation spectrometry, IC50=0.00089μM	20148564
MDA-MB-435	Growth inhibition assay		48 hrs	Growth inhibition of human MDA-MB-435 cells after 48 hrs by sulforhodamine B assay, GI50=0.067μM	20950898
IGROV1	Growth inhibition assay		48 hrs	Growth inhibition of human IGROV1 cells after 48 hrs by sulforhodamine B assay, GI50=0.095μM	20950898
MDA-MB-231	Growth inhibition assay		48 hrs	Growth inhibition of human MDA-MB-231cells after 48 hrs by sulforhodamine B assay, GI50=0.15μM	20950898
T47D	Growth inhibition assay		48 hrs	Growth inhibition of human T47D cells after 48 hrs by sulforhodamine B assay, GI50=0.44μM	20950898
MCF7	Growth inhibition assay		48 hrs	Growth inhibition of human MCF7 cells after 48 hrs by sulforhodamine B assay, GI50=0.7μM	20950898
OVCAR4	Growth inhibition assay		48 hrs	Growth inhibition of human OVCAR4 cells after 48 hrs by sulforhodamine B assay, GI50=0.88μM	20950898
BT549	Growth inhibition assay		48 hrs	Growth inhibition of human BT549 cells after 48 hrs by sulforhodamine B assay, GI50=0.89μM	20950898
SKOV3	Growth inhibition assay		48 hrs	Growth inhibition of human SKOV3 cells after 48 hrs by sulforhodamine B assay, GI50=1.09μM	20950898
NCI/ADR-RES	Growth inhibition assay		48 hrs	Growth inhibition of human NCI/ADR-RES cells after 48 hrs by sulforhodamine B assay, GI50=1.16μM	20950898
MDA-N	Growth inhibition assay		48 hrs	Growth inhibition of human MDA-N cells after 48 hrs by sulforhodamine B assay, GI50=1.61μM	20950898
OVCAR5	Growth inhibition assay		48 hrs	Growth inhibition of human OVCAR5 cells after 48 hrs by sulforhodamine B assay, GI50=1.62μM	20950898
Hs 578T	Growth inhibition assay		48 hrs	Growth inhibition of human Hs 578T cells after 48 hrs by sulforhodamine B assay, GI50=2.17μM	20950898
OVCAR8	Growth inhibition assay		48 hrs	Growth inhibition of human OVCAR8 cells after 48 hrs by sulforhodamine B assay, GI50=4.5μM	20950898
OVCAR3	Growth inhibition assay		48 hrs	Growth inhibition of human OVCAR3 cells after 48 hrs by sulforhodamine B assay, GI50=5.87μM	20950898
MCF7a	Cytotoxicity assay		10 days	Cytotoxicity against human MCF7a cells expressing Tet-off-3betaHSD1-Arom assessed as inhibition of TST-stimulated cell proliferation measured after 10 days, EC50=0.000004μM	22951074
V79MZh	Function assay			Inhibition of human CYP11B2 expressed in hamster V79MZh cells using [1,2-3H]-11-deoxy-corticosterone as substrate, IC50=1.42μM	23281812
V79MZh	Function assay			Inhibition of human CYP11B1 expressed in hamster V79MZh cells using [1,2-3H]-11-deoxy-corticosterone as substrate, IC50=2.62μM	23281812
H295R	Function assay	5 uM	24 hrs	Inhibition of CYP19 in human H295R cells using [1beta-3H(N)]-androst-4-ene-3,17-dione at 5 uM after 24 hrs by tritiated water release assay	24025069
MCF7	Cytotoxicity assay		72 hrs	Cytotoxicity against estrogen-dependent human MCF7 cells after 72 hrs by MTT assay, IC50=0.007μM	24345481
MCF7	Cytotoxicity assay		24 to 96 hrs	Cytotoxicity against human MCF7 cells after 24 to 96 hrs, IC50=0.02μM	24345481
JEG-3	Function assay			Inhibition of aromatase (unknown origin) expressed in JEG-3 cells, IC50=0.00089μM	25992880
insect cells	Function assay		30 mins	Inhibition of recombinant human CYP19 expressed in baculovirus infected insect cells using MFC as substrate measured after 30 mins by fluorometric analysis, IC50=0.0053μM	27647367
T47D	Function assay		24 hrs	Inhibition of aromatase activity in human T47D cells after 24 hrs, IC50=29.5μM	27770735
T47D	Function assay		24 hrs	Inhibition of aromatase activity in human T47D cells after 24 hrs, IC50=29.5μM	28427017
MCF7	Cytotoxicity assay		48 hrs	Cytotoxicity against human MCF7 cells after 48 hrs by MTT assay, IC50=4.73μM	29202405
MCF7	Growth inhibition assay		72 hrs	Growth inhibition of human MCF7 cells incubated for 72 hrs by cell counting based method, GI50=4.1μM	30822713
MDA-MB-231	Growth inhibition assay		72 hrs	Growth inhibition of human MDA-MB-231 cells incubated for 72 hrs by cell counting based method, GI50=10μM	30822713
insect cells	Function assay			Inhibition of recombinant human aromatase expressed in baculovirus infected insect cells using O-benzyl fluorescein benzyl ester as substrate in presence of NADPH generating system by fluorescence based analysis, IC50=0.0019μM	31416738
MCF-7aro	Function assay		1 hr	Inhibition of aromatase in human MCF-7aro cells using [1beta-3H] androstenedione as substrate incubated for 1 hr by liquid scintillation counting method, IC50=0.0019μM	31732252
insect cells	Function assay		30 mins	Inhibition of human recombinant aromatase expressed in baculovirus infected insect cells using O-benzylfluorescein benzyl ester as substrate after 30 mins, IC50=0.0011μM	ChEMBL
Klik om meer experimentele gegevens over cellijnen te bekijken

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

Molecuulgewicht	285.3	Formule	C₁₇H₁₁N₅	Opslag (vanaf de datum van ontvangst)	3 jaar-20°Cpoeder
CAS-nr.	112809-51-5	SDF downloaden		Opslag van stamoplossingen	1 jaar-80°Cin oplosmiddel 1 maand-20°Cin oplosmiddel
Synoniemen	CGS 20267			Smiles	C1=CC(=CC=C1C#N)C(C2=CC=C(C=C2)C#N)N3C=NC=N3

Oplosbaarheid (Solubility)

In vitro
Batch:

DMSO : 57 mg/mL (199.78 mM)
(Met vocht verontreinigd DMSO kan de oplosbaarheid verminderen. Gebruik verse, watervrije DMSO.)

Water : Insoluble

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.
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.	2.850mg/ml (9.99mM)	Taking the 1 mL working solution as an example, add 50 μL of 57 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.	0.450mg/ml (1.58mM)	Taking the 1 mL working solution as an example, add 50 μL of 9 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 (Mechanism of Action)

Targets/IC₅₀/Ki	Aromatase (Cell-free assay) 0.07 nM-20 nM
In vitro	Letrozole potently inhibits aromatase derived from a variety of different sources including human placental microsomes, particulate fractions of human breast cancer, rat ovarian microsomes, MCF-7 cells transfected with aromatase (MCF-7Ca), JEG-3 human choriocarcinoma cells , CHO cells, hamster ovarian tissue, and particulate fractions of human breast cancer with IC50 of 11, 2, 7, 0.07, 0.07, 1.4, 20 and 0.8 nM. In the non-cellular systems, the IC50 of this compound is calculated to be 1-13 nM. It maximally inhibits estradiol production in vitro in LH-stimulated hamster ovarian tissue at 0.1 μM with an IC50 of 0.02 μM and does not significantly affect progesterone production up to 350 μM. In ACTH-stimulated rat adrenal tissue in vitro, aldosterone production is inhibited by with an IC50 of 210 μM. This chemical inhibits growth of the MCF-7 epithelial breast cancer cells in a dose-dependent way with IC50 of 1 nM. Inhibition can be observesed even at the very low concentrations tested (0.1 nM). Treatment of normal MCF-12A epithelial cells with this compound did not affect their growth even when high letrozole concentrations (100 nM) or prolonged culture times. Concurrent administration of 17-β-estradiol with it (10 nM) decreased the stimulatory effect of the enzymatic activity of MMP-2 and - 9 released by estradiol.
Kinase Assay	Activiteit van humane placentaire aromatase
Kinase Assay	De test wordt uitgevoerd in een totaal volume van 1 ml bij 37 ℃. Tenzij anders vermeld, bevat het incubatiemengsel 11 nM [4- ¹⁴C] androstene-3, 17-dion ([4- ¹⁴C]A), 24 mM NADPH (tetranatriumzout Type III), de geschikte concentraties van de gewenste remmer en 120 μg microsomaal eiwit. Het (4- ¹⁴C)A wordt toegevoegd als een oplossing in 1,7% ethanol in 0,05 M kaliumfosfaatbuffer (pH 7,4), zodat de uiteindelijke concentratie ethanol niet meer dan 0,02% (v/v) bedraagt. De reactie wordt gestart door de toevoeging van enzym en na 20 min gestopt door de toevoeging van 7 vol ethylacetaat. Het mengsel wordt geschud op een vortexmixer en gedurende 5 min gecentrifugeerd bij 600 g. De waterige fase wordt opnieuw geëxtraheerd met 7 vol ethylacetaat, en de gecombineerde extracten worden tot droogte verdampt met behulp van een Evapo-Mix. Meer dan 99% van de radioactiviteit van toegevoegd [4- ¹⁴C] wordt teruggevonden met dit extractiesysteem. Het verkregen residu wordt opgelost in 150 μL aceton, en 100 μL aliquots worden gedurende 65 min gechromatografeerd op dunne-laagplaten voorbekleed met silicagel 60 met behulp van ethylacetaat: isooctaan (140:60, v/v; systeem A) of tolueen: chloroform: methanol (70:140:20; systeem B). De radioactieve zones van de plaat worden gelokaliseerd met een Berthold LB 2760 dunne-laagscanner. De radioactieve estradiol (E2) en estron (E1) pieken worden geïdentificeerd door vergelijking met authentieke standaarden. De corresponderende bindingsband van silicagel wordt overgebracht naar flacons die 10 mL scintillatievloeistof bevatten en geteld met een 6880 Liquid Scintillatiesysteem.
In vivo	Letrozole inhibits aromatase in vivo with ED50 of 1-3 μg/kg p.o.. This compound displays anti-endocrine effects. It inhibits androstenedione-induced uterine hypertrophy in immature rats with ED50 of 1-3 μg/kg. In the adult female rat, this compound (0.3-1 mg/kg daily p.o., 14 days) completely interrupts ovarian cyclicity and reduces uterine weight and serum estradiol (E2) concentrations to a similar extent to that seen after ovariectomy. This chemical induces dose-dependent regression of estrogen-dependent, 9,10-dimethylbenz-a-anthracene-induced mammary tumors in adult female rats. The ED50 for it is determined to be 10 - 30 µg/kg/day, with complete inhibition at a daily dose of 10 µg/day. It produces dose-dependent inhibition of tumor growth of MCF-7 cells transfected with human aromatase gene (MCF-7Ca) implanted athymic nude mice, with complete inhibition at 20 mg/kg per day p.o..
Referenties	[1] https://pubmed.ncbi.nlm.nih.gov/14630089/ [2] https://pubmed.ncbi.nlm.nih.gov/2149502/ [3] https://pubmed.ncbi.nlm.nih.gov/12569569/ [4] https://pubmed.ncbi.nlm.nih.gov/20095792/ [5] https://pubmed.ncbi.nlm.nih.gov/7628871/ [6] https://pubmed.ncbi.nlm.nih.gov/2973160/

Informatie over klinische proeven (Clinical Trial Information)

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

NCT-nummer	Werving	Aandoeningen	Sponsor/medewerkers	Startdatum	Fasen
NCT06143631	Not yet recruiting	Leiomyoma Uterine\|Leiomyoma\|Fibroid\|Fibroid Uterus	University of California San Francisco\|Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)	May 13 2024	Phase 4
NCT05872204	Recruiting	Low Grade Serous Ovarian Carcinoma\|Adult Type Granulosa Cell Tumor	Universitaire Ziekenhuizen KU Leuven\|Kom Op Tegen Kanker\|Eli Lilly and Company\|European Network of Gynaecological Oncological Trial Groups (ENGOT)	November 30 2023	Phase 2

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):

Letrozole Aromatase inhibitor

Chemische structuur

Molecuulgewicht: 285.3

Kwaliteitscontrole (Quality Control)

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

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

Oplosbaarheid (Solubility)

Molariteitscalculator

In vivo formulatiecalculator (heldere oplossing)

Werkingsmechanisme (Mechanism of Action)

Informatie over klinische proeven (Clinical Trial Information)

Letrozole Aromatase inhibitor

Chemische structuur

Molecuulgewicht: 285.3

Kwaliteitscontrole (Quality Control)

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

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

Oplosbaarheid (Solubility)

Molariteitscalculator

In vivo formulatiecalculator (heldere oplossing)

Werkingsmechanisme (Mechanism of Action)

Informatie over klinische proeven (Clinical Trial Information)

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