ウベニメクス

ウベニメクス
	IUPAC名 (2S)-2-[[(2S,3R)-3-Amino-2-hydroxy-4-phenylbutanoyl]amino]-4-methylpentanoic acid
	別称 Bestatin; N-[(2S,3R)-3-Amino-2-hydroxy-4-phenylbutyryl]-L-leucine
識別情報
CAS登録番号	58970-76-6, 65391-42-6 (HCl)
PubChem	72172
ChemSpider	65145
UNII	I0J33N5627
KEGG	D00087
ChEMBL	CHEMBL29292
	SMILES CC(C)C[C@@H](C(=O)O)NC(=O)[C@H]([C@@H](CC1=CC=CC=C1)N)O;
	InChI InChI=1S/C16H24N2O4/c1-10(2)8-13(16(21)22)18-15(20)14(19)12(17)9-11-6-4-3-5-7-11/h3-7,10,12-14,19H,8-9,17H2,1-2H3,(H,18,20)(H,21,22)/t12-,13+,14+/m1/s1 Key: VGGGPCQERPFHOB-RDBSUJKOSA-N; InChI=1/C16H24N2O4/c1-10(2)8-13(16(21)22)18-15(20)14(19)12(17)9-11-6-4-3-5-7-11/h3-7,10,12-14,19H,8-9,17H2,1-2H3,(H,18,20)(H,21,22)/t12-,13+,14+/m1/s1 Key: VGGGPCQERPFHOB-RDBSUJKOBZ;
特性
化学式	C16H24N2O4
モル質量	308.37 g mol−1
融点	245 °C, 518 K, 473 °F ((decomposes))
危険性
Sフレーズ	S22 S24/25
	特記なき場合、データは常温 (25 °C)・常圧 (100 kPa) におけるものである。

ウベニメクス（INN: Ubenimex）またはベスタチン (bestatin) は、競合的、可逆的プロテアーゼ阻害剤である。アルギニルアミノペプチダーゼ^[2]、ロイコトリエンA₄ヒドロラーゼ^[3]、膜アラニルアミノペプチダーゼ^[4]、ロイシル/シスチニルアミノペプチダーゼ^[5]^[6]、膜ジペプチダーゼを阻害する。急性骨髄性白血病^[7]やリンパ水腫^[8]の治療への利用が研究されている。Streptomyces abikoensisが産生する^[9]。ウベニメクスは、オキシトシン、バソプレッシン、エンケファリン、その他の様々なペプチドや化合物の酵素分解を阻害することが知られている。

Crystal structure of ubenimex — ロイコトリエンA₄ヒドロラーゼの結合ポケット中のウベニメクスの結晶構造。1HS6

出典

^ N-((2S,3R)-3-Amino-2-hydroxy-4-phenylbutyryl)-L-leucine at Sigma-Aldrich
^ Umezawa, H.; Aoyagi, T.; Suda, H.; Hamada, M.; Takeuchi, T. (1976). Bestatin, an inhibitor of aminopeptidase B, produced by actinomycetes.. pp. 97–99.
^ Muskardin, D.T.; Voelkel, N.F.; Fitzpatrick, F.A. (1994). Modulation of pulmonary leukotriene formation and perfusion pressure by Bestatin, an inhibitor of leukotriene A4 hydrolase.. pp. 131–137.
^ K Sekine; H Fujii; F Abe (1999). Induction of apoptosis by Bestatin (ubenimex) in human leukemic cell lines. 13. pp. 729–734.
^ “Immunoaffinity purification and characterization of native placental leucine aminopeptidase/oxytocinase from human placenta”. Placenta 21 (7): 628–34. (2000). doi:10.1053/plac.2000.0564. PMID 10985965.
^ “Oxytocin is hydrolyzed by an enzyme in human placenta that is identical to the oxytocinase of pregnancy serum”. Peptides 17 (2): 257–61. (1996). doi:10.1016/0196-9781(95)02124-8. PMID 8801531.
^ Hirayama, Y; Sakamaki, S; Takayanagi, N; Tsuji, Y; Sagawa, T; Chiba, H; Matsunaga, T; Niitsu, Y (2003). “Chemotherapy with ubenimex corresponding to patient age and organ disorder for 18 cases of acute myelogeneous leukemia in elderly patients--effects, complications and long-term survival”. Gan to kagaku ryoho. Cancer & chemotherapy 30 (8): 1113–8. PMID 12938265.
^ Tian, W; Rockson, S; Jiang, X; Kim, J; Begaye, A; Shuffle, EM; Tu, AB; Cribb, M et al. (2017). “Leukotriene B4 antagonism ameliorates experimental lymphedema”. Science Translational Medicine 9 (389): eaal3920. PMID 28490670.
^ Bauvois, B; Dauzonne, D (January 2006). “Aminopeptidase-N/CD13 (EC 3.4.11.2) inhibitors: Chemistry, biological evaluations, and therapeutic prospects”. Medicinal Research Reviews 26 (1): 88–130. doi:10.1002/med.20044. PMID 16216010.

外部リンク

The MEROPS online database for peptidases and their inhibitors: Bestatin

[1] N-((2S,3R)-3-Amino-2-hydroxy-4-phenylbutyryl)-L-leucine at Sigma-Aldrich

[2] Umezawa, H.; Aoyagi, T.; Suda, H.; Hamada, M.; Takeuchi, T. (1976). Bestatin, an inhibitor of aminopeptidase B, produced by actinomycetes.. pp. 97–99.

[3] Muskardin, D.T.; Voelkel, N.F.; Fitzpatrick, F.A. (1994). Modulation of pulmonary leukotriene formation and perfusion pressure by Bestatin, an inhibitor of leukotriene A4 hydrolase.. pp. 131–137.

[4] K Sekine; H Fujii; F Abe (1999). Induction of apoptosis by Bestatin (ubenimex) in human leukemic cell lines. 13. pp. 729–734.

[pmid10985965-5] “Immunoaffinity purification and characterization of native placental leucine aminopeptidase/oxytocinase from human placenta”. Placenta 21 (7): 628–34. (2000). doi:10.1053/plac.2000.0564. PMID 10985965.

[pmid8801531-6] “Oxytocin is hydrolyzed by an enzyme in human placenta that is identical to the oxytocinase of pregnancy serum”. Peptides 17 (2): 257–61. (1996). doi:10.1016/0196-9781(95)02124-8. PMID 8801531.

[7] Hirayama, Y; Sakamaki, S; Takayanagi, N; Tsuji, Y; Sagawa, T; Chiba, H; Matsunaga, T; Niitsu, Y (2003). “Chemotherapy with ubenimex corresponding to patient age and organ disorder for 18 cases of acute myelogeneous leukemia in elderly patients--effects, complications and long-term survival”. Gan to kagaku ryoho. Cancer & chemotherapy 30 (8): 1113–8. PMID 12938265.

[8] Tian, W; Rockson, S; Jiang, X; Kim, J; Begaye, A; Shuffle, EM; Tu, AB; Cribb, M et al. (2017). “Leukotriene B4 antagonism ameliorates experimental lymphedema”. Science Translational Medicine 9 (389): eaal3920. PMID 28490670.

[9] Bauvois, B; Dauzonne, D (January 2006). “Aminopeptidase-N/CD13 (EC 3.4.11.2) inhibitors: Chemistry, biological evaluations, and therapeutic prospects”. Medicinal Research Reviews 26 (1): 88–130. doi:10.1002/med.20044. PMID 16216010.

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関連項目

出典

外部リンク