UBENIMEX

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C16H24N2O4
Molecular Weight	308.3728
Optical Activity	( - )
Defined Stereocenters	3 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)C[C@H](NC(=O)[C@@H](O)[C@H](N)CC1=CC=CC=C1)C(O)=O

InChI

InChIKey=VGGGPCQERPFHOB-RDBSUJKOSA-N

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

HIDE SMILES / InChI

Description
Sources: http://www.eigerbio.com/resources/PR-15Dec2015.pdf | https://www.ncbi.nlm.nih.gov/pubmed/2223152

Ubenimex is a dipeptide, which specifically inhibits the activity of leukotriene A4 hydrolase, aminopeptidase B and leucine aminopeptidase of the cell membrane. The drug was isolated from Streptomyces oliooreticuli in 1976 in Nippon Kayaku, Japan and approved for the treatment of acute non-lymphocytic leukemia under the name Bestatin. In the USA the drug is currentlu in Phase II for the treatment of pulmonary arterial hypertension and lymphedema.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Leukotriene A-4 hydrolase 2 Target ID: P09960 Gene ID: 4048.0 Gene Symbol: LTA4H Target Organism: Homo sapiens (Human) Sources: http://www.eigerbio.com/resources/PR-15Dec2015.pdf	Inhibitor 8297	10.4 µM [IC50]
Cytosol aminopeptidase 2 Target ID: P28838 Gene ID: 51056.0 Gene Symbol: LAP3 Target Organism: Homo sapiens (Human) Sources: http://www.eigerbio.com/resources/PR-15Dec2015.pdf	Inhibitor 8297
Aminopeptidase B 2 Target ID: Q9H4A4 Gene ID: 6051.0 Gene Symbol: RNPEP Target Organism: Homo sapiens (Human) Sources: http://www.eigerbio.com/resources/PR-15Dec2015.pdf	Inhibitor 8297

Conditions

Condition	Modality	Highest Phase	Product
Acute non-lymphocytic leukemia 10 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8347731	Primary	Approved 8429	BESTATIN Approved Use Adjunct to chemotherapy agent to extend survival and to maintain remission after treatment for acute non-lymphocytic leukemia in adults. Launch Date 1987
Pulmonary arterial hypertension 35 Sources: https://www.clinicaltrials.gov/ct2/show/NCT02736149	Primary	Phase II 1132	Unknown Approved Use Unknown
Lymphedema 4 Sources: https://www.clinicaltrials.gov/ct2/show/NCT02700529	Primary	Phase II 1132	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Cryptosporidium parvum metalloaminopeptidase inhibitors prevent in vitro excystation.	1996 Dec	9124840
Bestatin-mediated inhibition of leucine aminopeptidase may hinder HIV infection.	1997 Dec	9477117
In vitro and in vivo evaluation of aminopeptidase inhibitors as antimicrosporidial therapies.	2001	11906096
Adult T-cell leukemia associated with gastric carcinoma: report of a case.	2001	11318127
[Effects of ubenimex ( bestatin) on the immunity of patients with squamous cell lung carcinoma treated with chemotherapy].	2001 Oct 20	21059319
Possible involvement of placental peptidases that degrade gonadotropin-releasing hormone (GnRH) in the dynamic pattern of placental hCG secretion via GnRH degradation.	2002 Jul	12137746
Induction of graft-versus-host disease and a graft-versus-leukemia effect using ubenimex in a patient with infantile leukemia relapsing after an unrelated cord blood transplant.	2002 Oct	12368960
[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].	2003 Aug	12938265
Aminopeptidase inhibitors inhibit proliferation and induce apoptosis of K562 and STI571-resistant K562 cell lines through the MAPK and GSK-3beta pathways.	2003 Nov	14738154
[A case of renal cell carcinoma with lymph node metastasis keeping remission for five years by adjuvant immunotherapy with ubenimex].	2003 Oct	14584289
Long-term cytogenetic remission with ubenimex monotherapy in a case of chronic myeloid leukemia.	2004 Aug	15269606
[Experimental study of the enhancement effect of aminopeptidase N inhibitor ubenimex on the differentiation induction activity of all-trans-retinoic acid in acute promyelocytic leukemia cells and its mechanism].	2006 Jul	17147245
CD13/Aminopeptidase N overexpression by basic fibroblast growth factor mediates enhanced invasiveness of 1F6 human melanoma cells.	2006 Jun 5	16685268
Complete remission induced by gemtuzumab ozogamicin in a Jehovah's Witness patient with acute myelogenous leukemia.	2007 Jun	17562618
Characterization of the catalytically active Mn(II)-loaded argE-encoded N-acetyl-L-ornithine deacetylase from Escherichia coli.	2007 Jun	17333302
Aminopeptidase B, a glucagon-processing enzyme: site directed mutagenesis of the Zn2+-binding motif and molecular modelling.	2007 Oct 31	17974014
Aminopeptidase N (APN)/CD13 inhibitor, Ubenimex, enhances radiation sensitivity in human cervical cancer.	2008 Mar 19	18366676
Stromal aminopeptidase N expression: correlation with angiogenesis in non-small-cell lung cancer.	2009 Nov	19908113
Idarubicin plus behenoyl cytarabine and 6-thioguanine compares favorably with idarubicin plus cytarabine-based regimen for children with previously untreated acute myeloid leukemia: 10-year retrospective, multicenter study in Korea.	2010 Jan	20052341
Synthesis of new (-)-bestatin-based inhibitor libraries reveals a novel binding mode in the S1 pocket of the essential malaria M1 metalloaminopeptidase.	2011 Mar 24	21366301
The aminopeptidase inhibitor CHR-2863 is an orally bioavailable inhibitor of murine malaria.	2012 Jun	22450967

Patents

Sample Use Guides

In Vivo Use Guide

Administer 30 mg ubenimex orally once a day.

Route of Administration: Oral

In Vitro Use Guide

MT-1, MOLT-4, HL-60, K562 and Raji cells were cultured in the presence of ubenimex (4.5, 45, 450 ug/ml and 4.5 mg/ml) at 37C. The number of viable HL-60 cells decreased with time at a high concentration of the drug (4.5 mg/ml) with time. The number of viable MT-1 cells was also decreased at the concentrations 4.5 mg/ml and 450 ug/ml. The number of viable MOLT-4 cells did not decrease even at high concentrations. The number of viable Raji cells also decreased at 4.5 mg/ml, but was not affected at 450 ug/ml.

Name

Type

Language

UBENIMEX

Official Name

English

UBENIMEX [MART.]

Common Name

English

ubenimex [INN]

Common Name

English

(-)-BESTATIN

Common Name

English

BESTATIN

Common Name

English

NSC-265489

Code

English

NK-421

Code

English

L-LEUCINE, N-((2S,3R)-3-AMINO-2-HYDROXY-1-OXO-4-PHENYLBUTYL)-

Systematic Name

English

N-((2S,3R)-3-AMINO-2-HYDROXY-4-PHENYLBUTANOYL)-LEUCINE

Systematic Name

English

Ubenimex [WHO-DD]

Common Name

English

UBENIMEX [JAN]

Common Name

English

UBENIMEX [MI]

Common Name

English

Classification Tree Code System Code

EU-Orphan Drug

EU/3/16/1638