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
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard
100.055.917
EC Number
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
C 16 H 24 N 2 O 4
Molar mass
308.378 g·mol−1
Melting point
245 °C (473 °F; 518 K) (decomposes)
Hazards
GHS labelling :[ 2]
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).
Chemical compound
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 in the binding pocket of leukotriene A4 hydrolase. Rendered from PDB 1HS6 .
See also
References
^ N-((2S,3R)-3-Amino-2-hydroxy-4-phenylbutyryl)-L-leucine at Sigma-Aldrich
^ "Ubenimex" . pubchem.ncbi.nlm.nih.gov . Retrieved 12 December 2021 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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; 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 .
^ 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 .
External links
The MEROPS online database for peptidases and their inhibitors: Bestatin
Receptor (ligands )
BLT Tooltip Leukotriene B4 receptor
BLT1 Tooltip Leukotriene B4 receptor 1 BLT2 Tooltip Leukotriene B4 receptor 2
CysLT Tooltip Cysteinyl leukotriene receptor
CysLT1 Tooltip Cysteinyl leukotriene receptor 1 CysLT2 Tooltip Cysteinyl leukotriene receptor 2 CysLTE Tooltip Cysteinyl leukotriene receptor E
Enzyme (inhibitors )
5-LOX Tooltip Arachidonate 5-lipoxygenase 12-LOX Tooltip Arachidonate 12-lipoxygenase 15-LOX Tooltip Arachidonate 15-lipoxygenase LTA4 H Tooltip Leukotriene A4 hydrolase LTB4 H Tooltip Leukotriene B4 ω-hydroxylase LTC4 S Tooltip Leukotriene C4 synthase LTC4 H Tooltip Leukotriene C4 hydrolase LTD4 Tooltip Leukotriene D4 hydrolase
Others