What Is Letrozole?

Letrozole, alias Fury, is a white or off-white chemical. Chemical name 1- [bis (4-cyanophenyl) methyl] -1,2,4-triazole; 4,4 '-(1 H-1,2,4-triazol-1-ylidene Methyl) -bisbenzonitrile with a molecular formula of C ₁₇ H ₁₁ N ₅ and a molecular weight of 285.31. It is a new generation of aromatase inhibitor. It is a synthetic benztriazole derivative. Letrozole can reduce the estrogen level by inhibiting aromatase, thereby eliminating the stimulating effect of estrogen on tumor growth. Endocrine therapy for breast cancer. ^[1]

Chinese name: Letrozole
Foreign name: Letrozole

CAS number: 112809-51-5
Molecular formula: C17H11N5

Letrozole Basic Information

Chinese name: Letrozole

Chinese alias: 1- [bis (4-cyanophenyl) methyl] -1,2,4-triazole; 4,4 '-(1 H-1,2,4-triazol-1-yl Methylene) -bisbenzonitrile

Letrozole, Fury

English name: Letrozole Tablets

English alias: 4,4 '-(1H-1,2,4-TRIAZOL-1-YLMETHYLENE) BIS-BENZONITRILE; CGS-20267; FEMARA; LETROZOL; LetrozoleUsp28; Letrozole99%; CGS-20267, Femara; LETRAZOLE; letrozolex; Lelrozol; 1- [BIS (4-CYANOPHENYL) METHYL] -1,2,4-TRIAZOLE; 4,4 '-(1H-1,2,4-Triazol-1-ylmethylene) dibenzonitrile; 4,4'-( 1H-1,2,4-Triazole-1-ylmethylene) bisbenzonitrile; 4,4 '-[(1H-1,2,4-Triazole-1-yl) methylene] dibenzonitrile

CAS number: 112809-51-5

Molecular formula: C ₁₇ H ₁₁ N ₅

Molecular weight: 285.31 ^[2]

Molecular structure diagram:

Letrozole molecular structure

Appearance white or off-white powder

181-183 ° C

Letrozole product uses

[Use one] Pyrrole aromatase inhibitor. Used to treat breast cancer. ^[2]

Letrozole Pharmacology and Toxicology

In vitro and in vivo studies have shown that letrozole can effectively inhibit the conversion of androgens to estrogen, while estrogen in postmenopausal women is mainly derived from the aromatization of androgen precursors in peripheral tissues, so it is particularly suitable for postmenopausal breast cancer patient. Letrozole is 150-250 times more potent than the first-generation aromatase inhibitor alumutide. Because of its high selectivity, it does not affect glucocorticoids, mineralocorticoids, and thyroid function. Large-dose use has no inhibitory effect on adrenal corticosteroid secretion, so it has a high therapeutic index. Various preclinical studies have shown that letrozole has no potential toxicity to various systems and target organs throughout the body, and has the characteristics of good tolerance and strong pharmacological effects. Compared with other aromatase inhibitors and anti-estrogen drugs, letrozole has a stronger antitumor effect ^[3] .

Letrozole Overview

Letrozole is a new generation of highly selective aromatase inhibitors. It is a synthetic benztriazole derivative. By inhibiting aromatase, the estrogen level is reduced, thereby eliminating the stimulating effect of estrogen on tumor growth. In vivo activity is 150-250 times stronger than that of the first generation aromatase inhibitor ammonialumetide. Because of its high selectivity, it does not affect glucocorticoids, mineralocorticoids, and thyroid function. Large-dose use has no inhibitory effect on adrenal corticosteroid secretion, so it has a high therapeutic index. Various preclinical studies have shown that letrozole has no potential toxicity, no mutagenic and carcinogenic effects on various systems and target organs throughout the body, and has less toxic side effects and is well tolerated. Compared with estrogen drugs, the antitumor effect is stronger. It is suitable for the treatment of postmenopausal patients with advanced breast cancer who have failed antiestrogen therapy and early treatment of breast cancer.
In December 2005, the UK drug and health product regulatory agency approved letrozole (furon) produced by Novartis, Switzerland for the treatment of breast cancer patients, allowing it to be used for surgically treated early menopausal hormone-positive aggressive breasts Cancer patients. This is the second aromatase inhibitor approved after AstraZeneca's Renin has been approved in the United Kingdom in June 2005. Both drugs have been shown in clinical trials to better prevent the risk of breast cancer recurrence compared to current standard tamoxifen treatment.
Letrozole tablets are different from anastrozole. Letrozole tablets are suitable for postmenopausal advanced breast cancer, and are mostly used for second-line treatment after failure of anti-estrogen therapy ^[1] .
Anastrozole: a powerful and selective triazole aromatase inhibitor, which can inhibit the aromatase dependent on cytochrome P-450 and block the biosynthesis of estrogen, which stimulates breast cancer cells The main factor of growth. The 50% inhibitory concentration (IC50) of this product on human placenta aromatase is 15nmol / L ^[3] .

Letrozole Drug Absorption

After oral letrozole, the drug was quickly completely absorbed in the gastrointestinal tract, reaching the highest serum concentration within 1 h, and was quickly distributed to the tissues. Serum protein binding rate is low, only 60%, and the terminal elimination phase of serum has a half-life of about 2 days. Its elimination is mainly through metabolism into hydroxyl metabolites without pharmacological effects. Almost all metabolites and about 5% of the original drug are excreted through the kidney ^[3] .

Letrozole adverse reactions

Randomized group trials showed that letrozole was taken orally 2.5 mg per day, and the incidence of possible adverse reactions related to the drug was 33%, which was significantly lower than 46% in the AG group. Letrozole's adverse reactions are mostly mild or moderate, with nausea (2% -9%), headache (0% -7%), bone pain (4% -10%), hot flashes (0% -9) %) And weight gain (2% to 8%) are the main manifestations. Other rare cases include constipation, diarrhea, pruritus, rash, joint pain, chest pain, abdominal pain, fatigue, insomnia, dizziness, edema, high blood pressure, and arrhythmia. , Thrombosis, dyspnea, vaginal bleeding, etc. ^[3] .

Letrozole indications

1. The treatment of advanced postmenopausal breast cancer (estrogen receptor, progesterone receptor positive or unknown receptor status), mostly used in second-line treatment after failure of anti-estrogen therapy;

2. First-line treatment for locally advanced or spread postmenopausal breast cancer (foreign data);

3. Extended adjuvant therapy for postmenopausal breast cancer patients who have received standard adjuvant therapy with tamoxifen for 5 years (foreign data);

4. Adjuvant therapy for early patients with hormone-positive breast cancer ^[3] .

Letrozole dosage

2.5 mg each time, orally, once daily. Gender, age, liver and kidney function have no clinically relevant relationship with letrozole, so elderly patients and patients with impaired liver and kidney function do not need to adjust the dose. According to many years of clinical experience, it also has an ovulation-promoting effect ^[3] .

Letrozole drug effect

The drug has not been improved in combination with tamoxifen or other aromatase inhibitors ^[3] .

Letrozole Specifications

2.5mg

Letrozole synthesis method

4-bromomethylbenzonitrile (I) and triazole are reacted in chloroform-acetonitrile, and the product (II) is reacted with 4-fluorobenzonitrile in the presence of potassium tert-butoxide in dimethylformamide, That is letrozole ^[2] .