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

Molecular Formula	C16H24N2O4
Molecular Weight	308.3728
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	3 / 3
E/Z Centers	0
Optical Activity	UNSPECIFIED

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

Ubenimex is a dipeptide, which specificallyinhibits 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 6 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 8504	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 8504
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 8504

Conditions

Condition	Modality	Highest Phase	Product
Acute non-lymphocytic leukemia 10 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8347731	Primary	Approved 8583	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 36 Sources: https://www.clinicaltrials.gov/ct2/show/NCT02736149	Primary	Phase II 1147	Unknown Approved Use Unknown
Lymphedema 4 Sources: https://www.clinicaltrials.gov/ct2/show/NCT02700529	Primary	Phase II 1147	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
7.1 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7840505/	150 mg 2 times / day multiple, oral dose: 150 mg route of administration: Oral experiment type: MULTIPLE co-administered:	UBENIMEX plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
2416.83 μg/L EXPERIMENT https://en.cnki.com.cn/Article_en/CJFDTotal-ZXYZ201206014.htm	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:	UBENIMEX plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
2.213 μg/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/530191_4299002M1034_1_005_1F.pdf#page=33	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:	UBENIMEX serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
3957.04 μg × h/L EXPERIMENT https://en.cnki.com.cn/Article_en/CJFDTotal-ZXYZ201206014.htm	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:		UBENIMEX plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
5.211 μg × h/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/530191_4299002M1034_1_005_1F.pdf#page=33	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:		UBENIMEX serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
2.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7840505/	150 mg 2 times / day multiple, oral dose: 150 mg route of administration: Oral experiment type: MULTIPLE co-administered:	UBENIMEX plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
3.49 h EXPERIMENT https://en.cnki.com.cn/Article_en/CJFDTotal-ZXYZ201206014.htm	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:	UBENIMEX plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
5.74 h OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/530191_4299002M1034_1_005_1F.pdf#page=33	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:	UBENIMEX serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
88.35% OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/530191_4299002M1034_1_005_1F.pdf#page=33			UBENIMEX serum	Homo sapiens

Doses

Dose	Population	Adverse events
900 mg 1 times / day multiple, oral Highest studied dose Dose: 900 mg, 1 times / day Route: oral Route: multiple Dose: 900 mg, 1 times / day Sources: https://www.sciencedirect.com/science/article/pii/B9780080279930500151	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: unknown Food Status: FED Sources: https://www.sciencedirect.com/science/article/pii/B9780080279930500151	Sources: https://www.sciencedirect.com/science/article/pii/B9780080279930500151

PubMed

Title	Date	PubMed
The aminopeptidase inhibitor CHR-2863 is an orally bioavailable inhibitor of murine malaria.	2012-06	22450967
Synthesis of new (-)-bestatin-based inhibitor libraries reveals a novel binding mode in the S1 pocket of the essential malaria M1 metalloaminopeptidase.	2011-03-24	21366301
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.	2010-01	20052341
Stromal aminopeptidase N expression: correlation with angiogenesis in non-small-cell lung cancer.	2009-11	19908113
Aminopeptidase N (APN)/CD13 inhibitor, Ubenimex, enhances radiation sensitivity in human cervical cancer.	2008-03-19	18366676
Aminopeptidase B, a glucagon-processing enzyme: site directed mutagenesis of the Zn2+-binding motif and molecular modelling.	2007-10-31	17974014
Complete remission induced by gemtuzumab ozogamicin in a Jehovah's Witness patient with acute myelogenous leukemia.	2007-06	17562618
Characterization of the catalytically active Mn(II)-loaded argE-encoded N-acetyl-L-ornithine deacetylase from Escherichia coli.	2007-06	17333302
[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].	2006-07	17147245
CD13/Aminopeptidase N overexpression by basic fibroblast growth factor mediates enhanced invasiveness of 1F6 human melanoma cells.	2006-06-05	16685268
Long-term cytogenetic remission with ubenimex monotherapy in a case of chronic myeloid leukemia.	2004-08	15269606
Aminopeptidase inhibitors inhibit proliferation and induce apoptosis of K562 and STI571-resistant K562 cell lines through the MAPK and GSK-3beta pathways.	2003-11	14738154
[A case of renal cell carcinoma with lymph node metastasis keeping remission for five years by adjuvant immunotherapy with ubenimex].	2003-10	14584289
[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].	2003-08	12938265
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.	2002-10	12368960
Possible involvement of placental peptidases that degrade gonadotropin-releasing hormone (GnRH) in the dynamic pattern of placental hCG secretion via GnRH degradation.	2002-07	12137746
[Effects of ubenimex ( bestatin) on the immunity of patients with squamous cell lung carcinoma treated with chemotherapy].	2001-10-20	21059319
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
Bestatin-mediated inhibition of leucine aminopeptidase may hinder HIV infection.	1997-12	9477117
Cryptosporidium parvum metalloaminopeptidase inhibitors prevent in vitro excystation.	1996-12	9124840

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.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 19:17:53 GMT 2025` Edited by `admin` on `Mon Mar 31 19:17:53 GMT 2025`
Record UNII	I0J33N5627
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

UBENIMEX

Official Name

English

NSC-265489

Preferred Name

English

UBENIMEX [MART.]

Common Name

English

ubenimex [INN]

Common Name

English

(-)-BESTATIN

Common Name

English

BESTATIN

Common Name

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