Toremifene

Các tên gọi khác (2) :

Toremifeno
Toremifenum

Thuốc điều trị ung thư

Thuốc Gốc

Small Molecule

CAS: 89778-26-7

ATC: L02BA02

ĐG : GTx Inc. , http://www.gtxinc.com

CTHH: C₂₆H₂₈ClNO

PTK: 405.96

A first generation nonsteroidal selective estrogen receptor modulator (SERM) that is structurally related to tamoxifen. Like tamoxifen, it is an estrogen agonist for bone tissue and cholesterol metabolism but is antagonistic on mammary and uterine tissue. [PubChem]

Nhận Dạng Quốc Tế & Đặc Tính Hóa Học

Công thức hóa học

C₂₆H₂₈ClNO

Phân tử khối

405.96

Monoisotopic mass

405.18594223

InChI

InChI=1S/C26H28ClNO/c1-28(2)19-20-29-24-15-13-23(14-16-24)26(22-11-7-4-8-12-22)25(17-18-27)21-9-5-3-6-10-21/h3-16H,17-20H2,1-2H3/b26-25-

InChI Key

InChIKey=XFCLJVABOIYOMF-QPLCGJKRSA-N

IUPAC Name

(2-{4-[(1Z)-4-chloro-1,2-diphenylbut-1-en-1-yl]phenoxy}ethyl)dimethylamine

Traditional IUPAC Name

toremifene

SMILES

CN(C)CCOC1=CC=C(C=C1)C(=C(\CCCl)C1=CC=CC=C1)\C1=CC=CC=C1

Độ tan chảy

108-110 °C

Độ hòa tan

4.09e-04 g/l

logP

6.8

logS

-6

pKa (Strongest Basic)

8.76

PSA

12.47 Å²

Refractivity

133.41 m³·mol^-1

Polarizability

46.49 Å³

Rotatable Bond Count

H Bond Acceptor Count

H Bond Donor Count

Physiological Charge

Number of Rings

Bioavailability

MDDR-Like Rule

true

Dược Lực Học : Toremifene is an antineoplastic hormonal agent primarily used in the treatment of advanced breast cancer. Toremifene is a nonsteroidal agent that has demonstrated potent antiestrogenic properties in animal test systems. The antiestrogenic effects may be related to its ability to compete with estrogen for binding sites in target tissues such as breast. Toremifene inhibits the induction of rat mammary carcinoma induced by dimethylbenzanthracene (DMBA) and causes the regression of already established DMBA-induced tumors. In this rat model, Toremifene appears to exert its antitumor effects by binding the estrogen receptors. In cytosols derived from human breast adenocarcinomas, Toremifene competes with estradiol for estrogen receptor protein.

Cơ Chế Tác Dụng : A first generation nonsteroidal selective estrogen receptor modulator (SERM) that is structurally related to tamoxifen. Like tamoxifen, it is an estrogen agonist for bone tissue and cholesterol metabolism but is antagonistic on mammary and uterine tissue. [PubChem] Toremifene is a nonsteroidal triphenylethylene derivative. Toremifene binds to estrogen receptors and may exert estrogenic, antiestrogenic, or both activities, depending upon the duration of treatment, animal species, gender, target organ, or endpoint selected. The antitumor effect of toremifene in breast cancer is believed to be mainly due to its antiestrogenic effects, in other words, its ability to compete with estrogen for binding sites in the cancer, blocking the growth-stimulating effects of estrogen in the tumor. Toremifene may also inhibit tumor growth through other mechanisms, such as induction of apoptosis, regulation of oncogene expression, and growth factors.

Dược Động Học :

▧ Absorption :
Well absorbed
▧ Volume of Distribution :
* 580 L
▧ Protein binding :
Toremifen is primarily bound to albumin (92%), 2% bound to α1-acid glycoprotein, and 6% bound to β1-globulin in the serum.
▧ Metabolism :
Hepatic. Mainly by CYP3A4 to N-demethyltoremifene, which exhibits antiestrogenic effects but has weak antitumor potency in vivo.
▧ Route of Elimination :
Toremifene is extensively metabolized, principally by CYP3A4 to N-demethyltoremifene, which is also antiestrogenic but with weak in vivo antitumor potency.
▧ Half Life :
5 days
▧ Clearance :
* 5 L/h

Chỉ Định : For the treatment of metastatic breast cancer in postmenopausal women with estrogen receptor-positive or receptor-unknown tumors. Toremifene is currently under investigation as a preventative agent for prostate cancer in men with high-grade prostatic intraepithelial neoplasia and no evidence of prostate cancer.

Tương Tác Thuốc :

Abarelix Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Amiodarone Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Amitriptyline Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Amoxapine Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Apomorphine Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Arsenic trioxide Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Artemether Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Asenapine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Chlorpromazine Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Cisapride Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Clarithromycin Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Clomipramine Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Conivaptan CYP3A4 Inhibitors (Strong) such as conivaptan may enhance the adverse/toxic effect of Toremifene. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Toremifene. Concurrent use of toremifene with strong CYP3A4 inhibitors should be avoided.
Dasatinib Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Desipramine Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Disopyramide Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Dofetilide Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Dolasetron Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Domperidone Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Doxepin Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Droperidol Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Erythromycin Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Etravirine Toremifene, when used concomitantly with etravirine, may experience a decrease in serum concentration. It is recommended to avoid concurrent therapy.
Flecainide Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Fluconazole Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Fluoxetine Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Flupentixol Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Foscarnet Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Gatifloxacin Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Halofantrine Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Haloperidol Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Ibutilide Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Imipramine Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Indapamide Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Isradipine Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Lapatinib Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Levofloxacin Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Loxapine Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Lumefantrine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Maprotiline Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Mefloquine Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Mesoridazine Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Methadone Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Moxifloxacin Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Nilotinib May cause additive QTc-prolonging effects. Concomitant therapy is contraindicated.
Norfloxacin Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Nortriptyline Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Octreotide Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Pazopanib Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.
Pentamidine Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Perflutren Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Pimozide Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Probucol Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Procainamide Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Propafenone Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Protriptyline Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Quetiapine Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Quinidine Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Quinine May cause additive QTc-prolonging effects. Concomitant therapy is contraindicated.
Ranolazine Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Rifabutin The rifamycin decreases the effect of anti-estrogen
Rifampicin The rifamycin decreases the effect of anti-estrogen
Risperidone Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Sotalol Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Sparfloxacin Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Sunitinib Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Tacrolimus Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Telithromycin Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Tetrabenazine May cause additive QTc-prolonging effects. Concomitant therapy is contraindicated.
Thioridazine May cause additive QTc-prolonging effects. Concomitant therapy is contraindicated.
Thiothixene Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Trimipramine Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Voriconazole Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Vorinostat Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Ziprasidone Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy should be avoided.
Zuclopenthixol Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.

Liều Lượng & Cách Dùng : Tablet - Oral

Dữ Kiện Thương Mại

Giá thị trường

Biệt dược thương mại : Fareston 60 mg tablet

Giá bán buôn : USD >11.84

Đơn vị tính : tablet

Nhà Sản Xuất

Công ty :

Sản phẩm biệt dược : Acapodene
Công ty :

Sản phẩm biệt dược : Fareston

Đóng gói

Công ty : GTx Inc.

Website : http://www.gtxinc.com

Tài Liệu Tham Khảo Thêm

drugbank

http://www.drugbank.ca/drugs/DB00539

PubChem Compound

http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=3005573

PubChem Substance

http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46506087

KEGG Compound

http://www.genome.jp/dbget-bin/www_bget?cpd:C08166

ChemSpider

http://www.chemspider.com/Chemical-Structure.2275722.html

National Drug Code Directory

http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/11399-005-30

PharmGKB

http://www.pharmgkb.org/drug/PA451731

Wikipedia

http://en.wikipedia.org/wiki/Toremifene

RxList

http://www.rxlist.com/cgi/generic2/toremifene.htm

Drugs.com

http://www.drugs.com/cdi/toremifene.html

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