Ubenimex

Ubenimex[1]
Names
IUPAC name
N-[(2S,3R)-3-Amino-2-hydroxy-4-phenylbutanoyl]-L-leucine
Systematic IUPAC name
(2S)-2-[(2S,3R)-3-Amino-2-hydroxy-4-phenylbutanamido]-4-methylpentanoic acid
Other names
Bestatin; N-[(2S,3R)-3-Amino-2-hydroxy-4-phenylbutyryl]-L-leucine
Identifiers
3D model (JSmol)
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.055.917 Edit this at Wikidata
EC Number
  • 261-529-2
KEGG
UNII
  • 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
  • CC(C)C[C@@H](C(=O)O)NC(=O)[C@H]([C@@H](CC1=CC=CC=C1)N)O
Properties
C16H24N2O4
Molar mass 308.378 g·mol−1
Melting point 245 °C (473 °F; 518 K) (decomposes)
Hazards
GHS labelling:[2]
GHS07: Exclamation mark
Warning
H315, H319, H335
P261, P264, P271, P280, P302+P352, P304+P340, P305+P351+P338, P312, P321, P332+P313, P337+P313, P362, P403+P233, P405
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
checkY verify (what is checkY☒N ?)

Ubenimex (INN), also known more commonly as bestatin, is a competitive, reversible protease inhibitor. It is an inhibitor of arginyl aminopeptidase (aminopeptidase B),[3] leukotriene A4 hydrolase (a zinc metalloprotease that displays both epoxide hydrolase and aminopeptidase activities),[4] alanyl aminopeptidase (aminopeptidase M/N),[5] leucyl/cystinyl aminopeptidase (oxytocinase/vasopressinase),[6][7] and membrane dipeptidase (leukotriene D4 hydrolase). It is being studied for use in the treatment of acute myelocytic leukemia[8] and lymphedema.[9] It is derived from Streptomyces olivoreticuli.[10] Ubenimex has been found to inhibit the enzymatic degradation of oxytocin, vasopressin, enkephalins, and various other peptides and compounds.[citation needed]

Crystal structure of ubenimex
Crystal structure of ubenimex in the binding pocket of leukotriene A4 hydrolase. Rendered from PDB 1HS6.
  1. ^ N-((2S,3R)-3-Amino-2-hydroxy-4-phenylbutyryl)-L-leucine at Sigma-Aldrich
  2. ^ "Ubenimex". pubchem.ncbi.nlm.nih.gov. Retrieved 12 December 2021.
  3. ^ Umezawa, H.; Aoyagi, T.; Suda, H.; Hamada, M.; Takeuchi, T. (1976). "Bestatin, an inhibitor of aminopeptidase B, produced by actinomycetes". The Journal of Antibiotics. 29 (29): 97–99. doi:10.7164/antibiotics.29.97. PMID 931798.
  4. ^ 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". Biochemical Pharmacology. 48 (48): 131–137. doi:10.1016/0006-2952(94)90232-1. PMID 8043014.
  5. ^ K Sekine; H Fujii; F Abe (1999). "Induction of apoptosis by Bestatin (ubenimex) in human leukemic cell lines". Leukemia. 13 (5): 729–734. doi:10.1038/sj.leu.2401388. PMID 10374877.
  6. ^ Nakanishi Y, Nomura S, Okada M, Ito T, Katsumata Y, Kikkawa F, Hattori A, Tsujimoto M, Mizutani S (2000). "Immunoaffinity purification and characterization of native placental leucine aminopeptidase/oxytocinase from human placenta". Placenta. 21 (7): 628–34. doi:10.1053/plac.2000.0564. PMID 10985965.
  7. ^ Naruki M, Mizutani S, Goto K, Tsujimoto M, Nakazato H, Itakura A, Mizuno K, Kurauchi O, Kikkawa F, Tomoda Y (1996). "Oxytocin is hydrolyzed by an enzyme in human placenta that is identical to the oxytocinase of pregnancy serum". Peptides. 17 (2): 257–61. doi:10.1016/0196-9781(95)02124-8. PMID 8801531. S2CID 28486489.
  8. ^ 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.
  9. ^ 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 (2017). "Leukotriene B4 antagonism ameliorates experimental lymphedema". Science Translational Medicine. 9 (389): eaal3920. doi:10.1126/scitranslmed.aal3920. PMID 28490670.
  10. ^ 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. PMC 7168514. PMID 16216010.