6-チオグアニン 化学特性,用途語,生産方法
外観
ほとんど白色〜うすい褐色, 粉末
溶解性
アルカリまたは酸に可溶、水に不溶。水酸化ナトリウム溶液に溶ける。
用途
阻害剤、薬理研究用。
効能
抗悪性腫瘍薬, 代謝拮抗薬
説明
6-Thioguanine (NSC 752, Thioguanine, 2-Amino-6-purinethiol), is an antineoplastic metabolic antagonist that inhibits DNA synthesis by being metabolically converted to 6-thioGMP. This inhibits purine biosynthesis at multiple steps, and may be phosphorylated and incorporated into DNA. In humans, it causes bone marrow depression and gastrointestinal toxicity. Due to safety problems it is currently less used as an antineoplastic agent but has some use as therapy for ulcerative colitis.
化学的特性
Crystalline, lyophilized, sterile, endot. It is white or slightly yellow powder with umami taste, easily soluble in water, but insoluble in organic solvents such as ethanol and acetone.
使用
6-Thioguanine acts as an antineoplastic and purine antimetabolite. It is also useful as an inhibition of stimulated expression of TNF-related apoptosis-inducing ligand (TRAIL) protein. It is involved in the treatment of acute leukemias and Psoriasis. Further, it is used for the treatment of ulcerative colitis and autoimmune diseases.
適応症
6-Thioguanine is a purine analogue structurally related
to 6-mercaptopurine and azathioprine. Thioguanine interferes
with several enzymes required for de novo
purine synthesis, and its metabolites are incorporated
into DNA and RNA, further impeding nucleic acid synthesis.
The mechanism of action of thioguanine in psoriasis
is not clearly understood; it has been hypothesized
to affect the proliferation and trafficking of lymphocytes
as well as the proliferation of keratinocytes.
主な応用
6-Thioguanine is a variant of guanine with hydrogen bonding at the N-7 of the purine ring. Its association with cytosine alters the dimension of the base stacking. 6-Thioguanine usage in treating inflammatory bowel disease (IBD) contributes to nodular regenerative hyperplasia (NRH) in the liver.
6-Thioguanine has been used:
to induce autophagy and apoptosis in colorectal cancer cell lines HCT116
as a selection marker in the mutation and survival assay in chinese hamster lung fibroblasts culture V79
as a selection marker in clonogenic Lung metastasis assay of 4T1-luc cells
定義
ChEBI: 6-Thioguanine is a 2-aminopurine that is the 6-thiono derivative of 2-amino-1,9-dihydro-6H-purine.
一般的な説明
6-thioguanine appears as odorless or almost odorless pale yellow crystalline powder. The drug is available in 40-mg tablets for oral use. It is used to treat acute nonlymphocytic leukemia.
空気と水の反応
6-Thioguanine may be sensitive to prolonged exposure to air. Insoluble in water.
反応プロフィール
6-Thioguanine is incompatible with strong oxidizing agents.
火災危険
Flash point data for 6-Thioguanine are not available; however, 6-Thioguanine is probably combustible.
作用機序
The mechanism of action involves incorporation of thetriphosphate into DNA and RNA, resulting in inhibition ofprocessing and function. Thioguanine is a purine antagonist. It is a pro-drug that is converted intracellullarly directly to thioguanine monophosphate (also called 6-thioguanylic acid) (TGMP) by the enzyme hypoxanthine-guanine phosphoribosyl transferase (HGPRT). TGMP is further converted to the di- and triphosphates, thioguanosine diphosphate (TGDP) and thioguanosine triphosphate (TGTP). The cytotoxic effect of thioguanine is a result of the incorporation of these nucleotides into DNA. Thioguanine has some immunosuppressive activity.1 Thioguanine is specific for the S phase of the cell cycle.
副作用
Dose-related myelosuppression is the major adverse
effect produced by 6-thioguanine. Patients deficient in
thiopurine methyltransferase (TPMT), a cytosolic enzyme
required for metabolism of 6-thioguanine, are at
heightened risk. Other adverse effects include gastrointestinal
complaints and elevations of liver transaminases.
There have been rare reports of more serious hepatotoxicity,
including acute hepatitis, acute cholestasis,
and hepatic venoocclusive disease.
安全性プロファイル
Poison by ingestion andintraperitoneal routes. Human mutation data reported. Anexperimental teratogen. Other reproductive effects. Ahuman skin irritant. When heated to decomposition itemits very toxic fumes of SOx and NOx.
純化方法
It crystallises from H2O as needles. It has UV at 258 and 347nm (H2O, pH 1) and 242, 270 and 322nm max (H2O, pH 11). [Elion & Hitchings J Am Chem Soc 77 1676 1955, Fox et al. J Am Chem Soc 80 1669 1958.] It is an antineoplastic agent [Kataoka et al. Cancer Res 44 519 1984]. [Beilstein 26 III/IV 3926.]
6-チオグアニン 上流と下流の製品情報
原材料
準備製品