Ubenimex

Ubenimex^[1]

Names
IUPAC name (2S)-2-[[(2S,3R)-3-Amino-2-hydroxy-4-phenylbutanoyl]amino]-4-methylpentanoic acid
Other names Bestatin; N-[(2S,3R)-3-Amino-2-hydroxy-4-phenylbutyryl]-L-leucine
Identifiers
CAS Number	58970-76-6 65391-42-6 (HCl)
ChEMBL	ChEMBL29292
ChemSpider	65145
Jmol interactive 3D	Image
PubChem	72172
UNII	I0J33N5627
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
SMILES CC(C)C[C@@H](C(=O)O)NC(=O)[C@H]([C@@H](CC1=CC=CC=C1)N)O
Properties
Chemical formula	C16H24N2O4
Molar mass	308.38 g·mol^−1
Melting point	245 °C (473 °F; 518 K) (decomposes)
Hazards
S-phrases	S22 S24/25
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references

Ubenimex (INN), also known more commonly as bestatin, is a competitive, reversible protease inhibitor. It is an inhibitor of arginyl aminopeptidase (aminopeptidase B),^[2] leukotriene A₄ hydrolase (a zinc metalloprotease that displays both epoxide hydrolase and aminopeptidase activities),^[3] alanyl aminopeptidase (aminopeptidase M/N),^[4] leucyl/cystinyl aminopeptidase (oxytocinase/vasopressinase),^[5][6] and membrane dipeptidase (leukotriene D₄ hydrolase). It is being studied for use in the treatment of acute myelocytic leukemia.^[7] It is derived from Streptomyces olivoreticuli.^[8] Ubenimex has been found to inhibit the enzymatic degradation of oxytocin, vasopressin, enkephalins, and various other peptides and compounds.

Crystal structure of ubenimex in the binding pocket of leukotriene A4 hydrolase. Rendered from PDB 1HS6.

See also

• Amastatin
• Pepstatin

References

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." (29): 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." (48): 131–137.
4. K Sekine, H Fujii and F Abe (1999). "Induction of apoptosis by Bestatin (ubenimex) in human leukemic cell lines" 13 (5): 729–734.
5. 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.
6. 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.
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. 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.

External links

• The MEROPS online database for peptidases and their inhibitors: Bestatin