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);
3D model (JSmol)	Interactive image;
ChEMBL	ChEMBL29292 ;
ChemSpider	65145;
ECHA InfoCard	100.055.917
PubChem CID	72172;
UNII	I0J33N5627 ;
CompTox Dashboard (EPA)	DTXSID4048430 ;
	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	308.378 g·mol−1
Melting point	245 °C (473 °F; 518 K) (decomposes)
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). verify (what is ?) 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.^{[citation needed]}

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

References

^ 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" (29): 97–99. {{cite journal}}: Cite journal requires |journal= (help)
^ 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. {{cite journal}}: Cite journal requires |journal= (help)
^ K Sekine; H Fujii; F Abe (1999). "Induction of apoptosis by Bestatin (ubenimex) in human leukemic cell lines". 13 (5): 729–734. {{cite journal}}: Cite journal requires |journal= (help)
^ 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.
^ 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.
^ 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

Template:Peptide receptor modulators

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[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. {{cite journal}}: Cite journal requires |journal= (help)

[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. {{cite journal}}: Cite journal requires |journal= (help)

[4] K Sekine; H Fujii; F Abe (1999). "Induction of apoptosis by Bestatin (ubenimex) in human leukemic cell lines". 13 (5): 729–734. {{cite journal}}: Cite journal requires |journal= (help)

[pmid10985965-5] 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.

[pmid8801531-6] 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.

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See also

References

External links