Eflornithine

Eflornithine C화학적 특성, 용도, 생산

개요

Metcalf et al.reported the synthesis of eflornithine (difluoromethyl ornithine [DFMO]) in 1978. Their interest arose from the desire to prepare ornithine decarboxylase (ODC) inhibitors as tools for studying the role of polyamines as regulators of growth processes. Ornithine decarboxylase catalyzes the conversion of ornithine to putrescine (1,4-diaminobutane), which in turn leads to the formation of the polyamines, spermine, and spermidine. It was not until 1980 that Bacchi et al. demonstrated the potential of DFMO in the treatment of trypanosomiasis.

용도

Labelled Eflornithine. Irreversible inhibitor of ornithine decarboxylase, an enzyme involved in polyamine biosynthesis. Antineoplastic; antipneumocystic; antiprotozoal (Trypanosoma). Used in the treatment of hirsutism.

Indications

Eflornithine (difluoromethyl ornithine, Ornidyl) is a unique antiprotozoal agent in that its mode of action involves inhibition of a specific enzyme, ornithine decarboxylase. In eukaryotes, decarboxylation of ornithine is required for biosynthesis of polyamines, which are important in cell division and differentiation.
Eflornithine is given intravenously, and about 80% of the drug is excreted in the urine within 24 hours. It does not bind significantly to plasma proteins and has a terminal plasma half-life of about 3 hours. It crosses the blood-brain barrier and is one of the drugs of choice for treating the hemolymphatic and meningoencephalitic stage of T. brucei-gambiense. The most significant side effects are anemia and leukopenia. Oral therapy is associated with considerable gastrointestinal toxicity. Diarrhea, thrombocytopenia, and seizures are occasionally reported.

Mechanism of action

Difluoromethyl ornithine is a suicide inhibitor of ODC, a pyridoxal phosphate–dependent enzyme. Evidence suggests that cysteine-360 in ODC is the site of eflornithine alkylation. Alkylation of ODC blocks the synthesis of putrescine, the rate-determining step in the synthesis of polyamines. Mammalian ODC also may be inhibited, but because the turnover of ODC is so rapid in mammals, eflornithine does not produce serious side effects.

Clinical Use

Eflornithine is used for the treatment of West African sleepingsickness, caused by Trypanosoma brucei gambiense.It is specifically indicated for the meningoencephaliticstage of the disease. Eflornithine is a myelosuppressivedrug that causes high incidences of anemia, leukopenia,and thrombocytopenia. Complete blood cell counts must bemonitored during the course of therapy.The irreversible inactivation of ornithine decarboxylaseby eflornithine is accompanied by decarboxylation andrelease of fluoride ion from the inhibitor, suggesting enzyme-catalyzed activation of the inhibitor. Only the (—) isomer,stereochemically related to L-ornithine, is active.
Eflornithine is supplied as the hydrochloride salt. It may beadministered either intravenously or orally. Approximately80% of the unchanged drug is excreted in the urine.Penetration of eflornithine into the CSF is facilitated by inflammationof the meninges.

부작용

Side effects reported for eflornithine consist of anemia, diarrhea, and leukopenia.

Eflornithine 준비 용품 및 원자재

원자재

준비 용품

Eflornithine 공급 업체

공급자	전화	이메일	국가	제품 수	이점
Hubei xin bonus chemical co. LTD	86-13657291602	linda@hubeijusheng.com	CHINA	22968	58
CONIER CHEM AND PHARMA LIMITED	+8618523575427	sales@conier.com	China	49390	58
Shaanxi Dideu Medichem Co. Ltd	+86-029-89586680 +86-18192503167	1026@dideu.com	China	9320	58
Dideu Industries Group Limited	+86-29-89586680 +86-15129568250	1026@dideu.com	China	29220	58
Dayang Chem (Hangzhou) Co.,Ltd.	571-88938639 +8617705817739	info@dycnchem.com	CHINA	52867	58
Hefei TNJ Chemical Industry Co.,Ltd.	0551-65418684 +8618949823763	sales@tnjchem.com	China	25363	58
GIHI CHEMICALS CO.,LIMITED	+8618058761490	info@gihichemicals.com	China	49999	58
Pure Chemistry Scientific Inc.	001-857-928-2050 or 1-888-588-9418	sales@chemreagents.com	United States	10194	62
Chemsky (shanghai) International Co.,Ltd	021-50135380	shchemsky@sina.com	China	15421	60
Hubei Jusheng Technology Co.,Ltd	027-59599241 18871490274	1400878000@qq.com	China	9972	58

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