乌苯美司

乌苯美司
临床资料
商品名（英语：Drug nomenclature）	百士欣等
其他名称	Bestatin; N-[(2S,3R)-3-Amino-2-hydroxy-4-phenylbutyryl]-L-leucine
AHFS/Drugs.com	国际药品名称
法律规范状态
法律规范	澳：未列入管制; 中：处方药 ;
药物动力学数据
药物代谢	肝脏
生物半衰期	2.1±0.7小时
排泄途径	尿
识别信息
	IUPAC命名法 N-[(2S,3R)-3-Amino-2-hydroxy-4-phenylbutanoyl]-L-leucine ; (2S)-2-[(2S,3R)-3-Amino-2-hydroxy-4-phenylbutanamido]-4-methylpentanoic acid（系统命名法）; ;
CAS号	65391-42-6（盐酸盐） ; 58970-76-6
PubChem CID	72172;
DrugBank	DB03424;
ChemSpider	65145;
UNII	I0J33N5627;
KEGG	D00087;
ChEMBL	ChEMBL29292 ;
CompTox Dashboard（英语：CompTox Chemicals Dashboard） (EPA)	DTXSID4048430 ;
ECHA InfoCard	100.055.917
化学信息
化学式	C16H24N2O4
摩尔质量	308.38 g·mol−1
3D模型（JSmol（英语：JSmol））	交互式图像;
熔点	245 °C（473 °F）
	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;

乌苯美司（INN：Ubenimex）^[4]，又名贝他定（英语：Bestatin），是一种竞争性、可逆性的蛋白酶抑制剂，最初由橄榄网状链霉菌（英语：Streptomyces abikoensis）（学名：Streptomyces olivoreticuli）培养滤液中分离得到^[2]^[5]^[6]。

乌苯美司是以下酶的抑制剂：

氨基肽酶B（英语：Aminopeptidase B）^[7]
白三烯A4水解酶（英语：Leukotriene-A4 hydrolase）（一种具有环氧化物水解酶（英语：Epoxide hydrolase）和氨基肽酶（英语：Aminopeptidase）活性的双功能锌酶）^[8]
丙氨酸氨肽酶（氨基肽酶M/N）^[9]
亮氨酰/半胱氨酰氨肽酶（英语：Insulin regulated aminopeptidase）（催产素酶/抗利尿激素酶）^[10]^[11]
‌膜二肽酶（英语：Membrane dipeptidase）（白三烯D₄水解酶）

用途

乌苯美司正在被研究用于治疗急性骨髓性白血病^[12]和淋巴水肿^[13]。由于乌苯美司是免疫调节剂，可增强T细胞功能^[2]，它也被研究作为HIV-1 DNA疫苗接种的免疫佐剂^[14]。

参见

胃酶抑素
Amastatin（英语：Amastatin）

参考文献

^ STANDARD FOR THE UNIFORM SCHEDULING OF MEDICINES AND POISONS. Federal Register of Legislation. 2020-10 [2021-08-15]. （原始内容存档于2021-01-25）.
^ ^2.0 ^2.1 ^2.2 ^2.3 ^2.4 乌苯美司片（西安万隆）. 丁香园·用药助手. [2025-03-16].
^ Ueda T, Tohyama K, Wano Y, Tsutani H, Fukushima T, Iwasaki H, Urasaki Y, Gotoh N, Kimura S, Okumura E; et al. Pharmacokinetic and clinical pilot study of high-dose intermittent ubenimex treatment in patients with myelodysplastic syndrome. Anticancer Res. 1994 Sep-Oct, 14 (5B): 2093–7. PMID 7840505.
^ N-((2S,3R)-3-Amino-2-hydroxy-4-phenylbutyryl)-L-leucine at Sigma-Aldrich
^ Abe F, Alvord G, Koyama M, Matsuda A, Talmadge JE. Pharmacokinetics of bestatin and oral activity for treatment of experimental metastases 28 (1): 29–33. 1989-01 [2025-03-16]. PMC 11038206 . PMID 2909281. doi:10.1007/BF00205797.
^ Bauvois, B; Dauzonne, D. Aminopeptidase-N/CD13 (EC 3.4.11.2) inhibitors: Chemistry, biological evaluations, and therapeutic prospects. Medicinal Research Reviews. January 2006, 26 (1): 88–130. PMC 7168514 . PMID 16216010. doi:10.1002/med.20044.
^ Umezawa, H.; Aoyagi, T.; Suda, H.; Hamada, M.; Takeuchi, T. Bestatin, an inhibitor of aminopeptidase B, produced by actinomycetes.. The Journal of Antibiotics. 1976, 29 (29): 97–99. PMID 931798. doi:10.7164/antibiotics.29.97 .
^ Muskardin, D.T.; Voelkel, N.F.; Fitzpatrick, F.A. Modulation of pulmonary leukotriene formation and perfusion pressure by Bestatin, an inhibitor of leukotriene A4 hydrolase.. Biochemical Pharmacology. 1994, 48 (48): 131–137. PMID 8043014. doi:10.1016/0006-2952(94)90232-1.
^ K Sekine; H Fujii; F Abe. Induction of apoptosis by Bestatin (ubenimex) in human leukemic cell lines. Leukemia. 1999, 13 (5): 729–734. PMID 10374877. doi:10.1038/sj.leu.2401388 .
^ Nakanishi Y, Nomura S, Okada M, Ito T, Katsumata Y, Kikkawa F, Hattori A, Tsujimoto M, Mizutani S. Immunoaffinity purification and characterization of native placental leucine aminopeptidase/oxytocinase from human placenta. Placenta. 2000, 21 (7): 628–34. PMID 10985965. doi:10.1053/plac.2000.0564.
^ Naruki M, Mizutani S, Goto K, Tsujimoto M, Nakazato H, Itakura A, Mizuno K, Kurauchi O, Kikkawa F, Tomoda Y. Oxytocin is hydrolyzed by an enzyme in human placenta that is identical to the oxytocinase of pregnancy serum. Peptides. 1996, 17 (2): 257–61. PMID 8801531. S2CID 28486489. doi:10.1016/0196-9781(95)02124-8.
^ Hirayama, Y; Sakamaki, S; Takayanagi, N; Tsuji, Y; Sagawa, T; Chiba, H; Matsunaga, T; Niitsu, Y. 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. 2003, 30 (8): 1113–8. PMID 12938265.
^ Tian, W; Rockson, S; Jiang, X; Kim, J; Begaye, A; Shuffle, EM; Tu, AB; Cribb, M; Nepiyushchikh, Z; Feroze, AH; Zamanian, RT; Dhillon, RT; Voelkel, NF; Peters-Golden, M; Kitajewski, J; Dixon, JB; Nicolls, MR. Leukotriene B4 antagonism ameliorates experimental lymphedema. Science Translational Medicine. 2017, 9 (389): eaal3920. PMID 28490670. doi:10.1126/scitranslmed.aal3920 .
^ Sasaki S, Fukushima J, Hamajima K, Ishii N, Tsuji T, Xin KQ, Mohri H, Okuda K. Adjuvant effect of Ubenimex on a DNA vaccine for HIV-1 111 (1): 30–35. 1998-01 [2025-03-16]. PMC 1904860 . PMID 9472658. doi:10.1046/j.1365-2249.1998.00466.x.

外部链接

The MEROPS online database for peptidases and their inhibitors: Bestatin

这是一篇与药学相关的小作品。您可以通过编辑或修订扩充其内容。

[1] STANDARD FOR THE UNIFORM SCHEDULING OF MEDICINES AND POISONS. Federal Register of Legislation. 2020-10 [2021-08-15]. （原始内容存档于2021-01-25）.

[dxy-2] 2.0 ^2.1 ^2.2 ^2.3 ^2.4 乌苯美司片（西安万隆）. 丁香园·用药助手. [2025-03-16].

[3] Ueda T, Tohyama K, Wano Y, Tsutani H, Fukushima T, Iwasaki H, Urasaki Y, Gotoh N, Kimura S, Okumura E; et al. Pharmacokinetic and clinical pilot study of high-dose intermittent ubenimex treatment in patients with myelodysplastic syndrome. Anticancer Res. 1994 Sep-Oct, 14 (5B): 2093–7. PMID 7840505.

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

[5] Abe F, Alvord G, Koyama M, Matsuda A, Talmadge JE. Pharmacokinetics of bestatin and oral activity for treatment of experimental metastases 28 (1): 29–33. 1989-01 [2025-03-16]. PMC 11038206 . PMID 2909281. doi:10.1007/BF00205797.

[6] Bauvois, B; Dauzonne, D. Aminopeptidase-N/CD13 (EC 3.4.11.2) inhibitors: Chemistry, biological evaluations, and therapeutic prospects. Medicinal Research Reviews. January 2006, 26 (1): 88–130. PMC 7168514 . PMID 16216010. doi:10.1002/med.20044.

[7] Umezawa, H.; Aoyagi, T.; Suda, H.; Hamada, M.; Takeuchi, T. Bestatin, an inhibitor of aminopeptidase B, produced by actinomycetes.. The Journal of Antibiotics. 1976, 29 (29): 97–99. PMID 931798. doi:10.7164/antibiotics.29.97 .

[8] Muskardin, D.T.; Voelkel, N.F.; Fitzpatrick, F.A. Modulation of pulmonary leukotriene formation and perfusion pressure by Bestatin, an inhibitor of leukotriene A4 hydrolase.. Biochemical Pharmacology. 1994, 48 (48): 131–137. PMID 8043014. doi:10.1016/0006-2952(94)90232-1.

[9] K Sekine; H Fujii; F Abe. Induction of apoptosis by Bestatin (ubenimex) in human leukemic cell lines. Leukemia. 1999, 13 (5): 729–734. PMID 10374877. doi:10.1038/sj.leu.2401388 .

[pmid10985965-10] Nakanishi Y, Nomura S, Okada M, Ito T, Katsumata Y, Kikkawa F, Hattori A, Tsujimoto M, Mizutani S. Immunoaffinity purification and characterization of native placental leucine aminopeptidase/oxytocinase from human placenta. Placenta. 2000, 21 (7): 628–34. PMID 10985965. doi:10.1053/plac.2000.0564.

[pmid8801531-11] Naruki M, Mizutani S, Goto K, Tsujimoto M, Nakazato H, Itakura A, Mizuno K, Kurauchi O, Kikkawa F, Tomoda Y. Oxytocin is hydrolyzed by an enzyme in human placenta that is identical to the oxytocinase of pregnancy serum. Peptides. 1996, 17 (2): 257–61. PMID 8801531. S2CID 28486489. doi:10.1016/0196-9781(95)02124-8.

[12] Hirayama, Y; Sakamaki, S; Takayanagi, N; Tsuji, Y; Sagawa, T; Chiba, H; Matsunaga, T; Niitsu, Y. 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. 2003, 30 (8): 1113–8. PMID 12938265.

[13] Tian, W; Rockson, S; Jiang, X; Kim, J; Begaye, A; Shuffle, EM; Tu, AB; Cribb, M; Nepiyushchikh, Z; Feroze, AH; Zamanian, RT; Dhillon, RT; Voelkel, NF; Peters-Golden, M; Kitajewski, J; Dixon, JB; Nicolls, MR. Leukotriene B4 antagonism ameliorates experimental lymphedema. Science Translational Medicine. 2017, 9 (389): eaal3920. PMID 28490670. doi:10.1126/scitranslmed.aal3920 .

[14] Sasaki S, Fukushima J, Hamajima K, Ishii N, Tsuji T, Xin KQ, Mohri H, Okuda K. Adjuvant effect of Ubenimex on a DNA vaccine for HIV-1 111 (1): 30–35. 1998-01 [2025-03-16]. PMC 1904860 . PMID 9472658. doi:10.1046/j.1365-2249.1998.00466.x.

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