Letrozole

別名: CGS 20267 中文名稱：來曲唑

目錄號(hào)：S1235 Purity: 99.99%

Letrozole是第三代aromatase抑制劑，無細(xì)胞試驗(yàn)中IC50為0.07-20 nM。在臨床研究中，對(duì)17α-OH progesterone、TSH、促黃體激素、促卵泡激素或雄烯二酮的血漿濃度沒有作用，不影響正常的尿電解質(zhì)排泄或甲狀腺功能。Letrozole 可誘導(dǎo)自噬。

Letrozole Chemical Structure

CAS: 112809-51-5

規(guī)格	價(jià)格	庫(kù)存
10mM (1mL in DMSO)	3930.28	現(xiàn)貨
25mg	814.34	現(xiàn)貨
100mg	2350.53	現(xiàn)貨
1g	7944.3	現(xiàn)貨
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產(chǎn)品質(zhì)控

批次：純度： 99.99%

99.99

Letrozole相關(guān)產(chǎn)品

相關(guān)產(chǎn)品	Fadrozole (CGS16949A) Obacunone (AI3-37934)	點(diǎn)擊展開
相關(guān)化合物庫(kù)	FDA藥物庫(kù) 天然產(chǎn)物庫(kù) 已知活性藥物庫(kù)-I 外泌體分泌相關(guān)化合物庫(kù) 人類激素相關(guān)化合物庫(kù)	點(diǎn)擊展開

細(xì)胞實(shí)驗(yàn)數(shù)據(jù)示例

細(xì)胞系	實(shí)驗(yàn)類型	給藥濃度	孵育時(shí)間	活性描述	文獻(xiàn)信息
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
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
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
MCF7	Cytotoxicity assay		48 hrs	Cytotoxicity against human MCF7 cells after 48 hrs by MTT assay, IC50=4.73μM	29202405
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
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
MCF7	Cytotoxicity assay		24 to 96 hrs	Cytotoxicity against human MCF7 cells after 24 to 96 hrs, IC50=0.02μM	24345481
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
MCF7	Cytotoxicity assay		72 hrs	Cytotoxicity against estrogen-dependent human MCF7 cells after 72 hrs by MTT assay, IC50=0.007μM	24345481
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
OVCAR3	Growth inhibition assay		48 hrs	Growth inhibition of human OVCAR3 cells after 48 hrs by sulforhodamine B assay, GI50=5.87μM	20950898
OVCAR8	Growth inhibition assay		48 hrs	Growth inhibition of human OVCAR8 cells after 48 hrs by sulforhodamine B assay, GI50=4.5μM	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
OVCAR5	Growth inhibition assay		48 hrs	Growth inhibition of human OVCAR5 cells after 48 hrs by sulforhodamine B assay, GI50=1.62μM	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
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
SKOV3	Growth inhibition assay		48 hrs	Growth inhibition of human SKOV3 cells after 48 hrs by sulforhodamine B assay, GI50=1.09μM	20950898
BT549	Growth inhibition assay		48 hrs	Growth inhibition of human BT549 cells after 48 hrs by sulforhodamine B assay, GI50=0.89μM	20950898
OVCAR4	Growth inhibition assay		48 hrs	Growth inhibition of human OVCAR4 cells after 48 hrs by sulforhodamine B assay, GI50=0.88μM	20950898
MCF7	Growth inhibition assay		48 hrs	Growth inhibition of human MCF7 cells after 48 hrs by sulforhodamine B assay, GI50=0.7μM	20950898
T47D	Growth inhibition assay		48 hrs	Growth inhibition of human T47D cells after 48 hrs by sulforhodamine B assay, GI50=0.44μM	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
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-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
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
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
JEG-3	Function assay			Inhibition of aromatase (unknown origin) expressed in JEG-3 cells, IC50=0.00089μM	25992880
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
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
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
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生物活性

產(chǎn)品描述

靶點(diǎn)

Aromatase ^[1]
(Cell-free assay)

0.07 nM-20 nM

體外研究(In Vitro)
體外研究活性	Letrozole有效抑制不同來源的芳香酶，包括人胎盤微粒體，人乳腺癌顆粒部分，大鼠卵巢微粒體，轉(zhuǎn)染芳香酶的MCF-7細(xì)胞(MCF-7Ca)，JEG-3絨膜癌細(xì)胞，CHO細(xì)胞，倉(cāng)鼠卵巢組織，人乳腺癌顆粒部分，IC50分別是11, 2, 7, 0.07, 0.07, 1.4, 20和 0.8 nM。在非細(xì)胞系統(tǒng)中，letrozole 的IC50是1-13 nM。^[1]Letrozole在LH誘導(dǎo)的倉(cāng)鼠卵巢組織中抑制雌二醇產(chǎn)生，IC50 是0.02 μM，達(dá)到350 μM濃度時(shí)，不顯著影響孕酮的產(chǎn)生。在ACTH誘導(dǎo)的大鼠腎組織中，抑制醛甾酮的產(chǎn)生，IC50 是210 μM. ^[2] Letrozole以劑量依賴的方式抑制MCF-7乳腺癌細(xì)胞的生長(zhǎng)，IC50是1 nM。在低濃度下(0.1 nM)抑制作用依然可以觀測(cè)到。letrozole 處理MCF-12A不影響生長(zhǎng)，即使letrozole 濃度達(dá)到 (100 nM)或者延長(zhǎng)培養(yǎng)時(shí)間。Letrozole (10 nM) 顯著抑制4-雄甾烯-3,17-二酮(100 nM) 或者睪酮 (100 nM) 對(duì)MCF-7在細(xì)胞增殖方面的激活作用。聯(lián)合使用17-β-雌二醇和letrozole (10 nM)降低由雌二醇誘導(dǎo)的MMP-2和MMP-9的活化作用。^[3]
激酶實(shí)驗(yàn)	人類胎盤芳香酶活性
激酶實(shí)驗(yàn)	反應(yīng)在37℃條件下，總體積為1 mL的體系中進(jìn)行。孵育的混合物包含11 nM [4- ¹⁴C] 雄甾烯-3, 17-二酮([4- ¹⁴C]A)，24 mM NADPH (焦磷酸鈉鹽III型)，適當(dāng)濃度的化合物，120 μg微粒體蛋白。(4- ¹⁴C)A用含有1.7% 溶解，溶于的0.05 M 磷酸鉀緩沖液 (pH 7.4)溶解，乙醇終濃度不超過0.02%。加入酶觸發(fā)反應(yīng)，20分鐘后加入7倍體積乙酸乙酯終止反應(yīng)?；旌衔镎鹗?，600g離心5分鐘。用7倍體積的乙酸乙酯重新提起，混合兩次所得樣品，Evapo-Mix蒸干。用這種方法，99%的[4- ¹⁴C]的放射性能夠保留。獲得的殘?jiān)苡?50ul丙酮，取100ul做65分鐘的薄層層析，用體積比為140:60的乙酸乙酯：異辛烷或者體積比為70:140:20（系統(tǒng)B）。用Berthold LB 2760定位放射性區(qū)域。放射性標(biāo)記的雌二醇和孕酮通過與標(biāo)準(zhǔn)品比對(duì)來確認(rèn)。硅膠結(jié)合的條帶轉(zhuǎn)移到10ml閃爍緩沖液中，用6880液體閃爍法系統(tǒng)計(jì)數(shù)。
細(xì)胞實(shí)驗(yàn)	細(xì)胞系	人類乳腺癌細(xì)胞 MCF-7
	濃度	~100 nM
	孵育時(shí)間	1天
	方法	細(xì)胞以5,000 到10,000個(gè)每孔的密度接種于24孔板上，第二天，加入不同濃度的Letrozole。孵育末期，細(xì)胞用胰酶消化，用Coulter particle計(jì)數(shù)器計(jì)數(shù)。

體內(nèi)研究(In Vivo)
體內(nèi)研究活性	在體內(nèi)實(shí)驗(yàn)中， Letrozole抑制芳香酶活性，口服ED50 是1-3 微克/毫克。^[2] Letrozole具有抗內(nèi)分泌效果。在未成年大鼠體內(nèi)，Letrozole抑制雄烯二酮引起的子宮肥大，ED50 為1-3 微克/千克。在成年雌性大鼠體內(nèi)，Letrozole (0.3-1 毫克/千克每天口服，14 天)完全打斷卵巢周期，并降低子宮重量和血清雌二醇(E2)濃度，使其與切除卵巢后的水平相同。^[1] Letrozole誘導(dǎo)劑量依賴的雌激素依賴的抑制9,10-二甲苯-a-蒽誘導(dǎo)的雌性大鼠的腫瘤。Letrozole 的ED50是10-30 微克/千克/天，完全抑制的劑量是10微克/天。^[4]
動(dòng)物實(shí)驗(yàn)	Animal Models	含有人類芳香化酶基因(MCF-7Ca)的人類乳腺癌異種移植MCF-7
	Dosages	20毫克/千克/天
	Administration	口服

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試驗(yàn)信息 (data from https://clinicaltrials.gov, updated on 2024-05-22)
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

參考文獻(xiàn)
[1] Haynes BP, et al. J Steroid Biochem Mol Biol, 2003, 87(1), 35-45. [2] Bhatnagar AS, et al. J Steroid Biochem Mol Biol, 1990, 37(6), 1021-1027. [3] Mitropoulou TN, et al. Int J Cancer, 2003, 104(2), 155-160. [4] Dellapasqua S, et al. Expert Opin Drug Metab Toxicol, 2010, 6(2), 251-259. [5] Lee K, et al. Int J Cancer, 1995, 62(3), 297-302. [6] Steele RE, et al. Steroids, 1987, 50(1-3), 147-161. + 展開

參考文獻(xiàn)

[1] Haynes BP, et al. J Steroid Biochem Mol Biol, 2003, 87(1), 35-45.
[2] Bhatnagar AS, et al. J Steroid Biochem Mol Biol, 1990, 37(6), 1021-1027.
[3] Mitropoulou TN, et al. Int J Cancer, 2003, 104(2), 155-160.

[4] Dellapasqua S, et al. Expert Opin Drug Metab Toxicol, 2010, 6(2), 251-259.
[5] Lee K, et al. Int J Cancer, 1995, 62(3), 297-302.
[6] Steele RE, et al. Steroids, 1987, 50(1-3), 147-161.

+ 展開