CAS 58970-76-6|Ubenimex

Introduction：Basic information about CAS 58970-76-6|Ubenimex, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Table of Contents

1. Names
2. Ubenimex BiologicalActivity
3. Chemical & Physical Properties
4. Toxicological Information
CHEMICAL IDENTIFICATION
HEALTH HAZARD DATA
ACUTE TOXICITY DATA
5. Safety Information
6. Articles26
7. Synonyms

Common Name	Ubenimex
CAS Number	58970-76-6	Molecular Weight	308.373
Density	1.2±0.1 g/cm3	Boiling Point	604.7±55.0 °C at 760 mmHg
Molecular Formula	C₁₆H₂₄N₂O₄	Melting Point	245 °C (dec.)(lit.)
MSDS	ChineseUSA	Flash Point	319.5±31.5 °C

Names

Name	Ubenimex
Synonym	More Synonyms

Ubenimex BiologicalActivity

Description	Bestatin is a natural, broad-spectrum, and competitive aminopeptidase inhibitor.
Related Catalog	Signaling Pathways >>Metabolic Enzyme/Protease >>AminopeptidaseResearch Areas >>Cancer
In Vitro	Bestatin enhances ATRA-induced differentiation and inhibits ATRA-driven phosphorylation of p38 MAPK in ATRA-sensitive APL NB4 cells. Bestatin can not reverse the differentiation block in ATRA-resistant APL MR2 cells. CD13 ligation with anti-CD13 antibody WM-15 results in phosphorylation of p38 MAPK, reduces the inhibition of Bestatin on the phosphorylation of p38 MAPK, and completely abolishes the enhancement of Bestatin on ATRA-inducing differentiation in NB4 cells[2]. Bestatin (600 μM)-treated cells progress slower through the cell cycle due to decreased rate of cell growth and the frequency of cell division. Bestatin inhibits the frequency of mitosis and the inherent multinuclearity in D. discoideum, and is not cytotoxic to D. discoideum cells at 0-600 μM. Bestatin inhibits aminopeptidase activity in lysates of PsaA-GFP- and GFP-expressing cells by 69.39% ± 10.5% and 39.93% ± 18.7% of control, respectively[4].
In Vivo	Bestatin (20 μM) significantly reduces CD13 expression in diabetic mice and results a significant inhibition of MMP-9 specific gelationolytic band densities compared to diabetic vehicle-treated mice. Bestatin treatment significantly inhibits the expression of VEGF and heparanase in diabetic mice. Intravitreal bestatin treatment significantly downregulates the expression of both HIF-1α and VEGF in diabetic mice retinas. Furthermore, the upregulated expression of heparanase in diabetic mice retinas is significantly inhibited by intravitreal bestatin treatment[1]. Bestatin (10, 1, and 0.1mg/kg, i.p.) treatment before the antigen-potentiated humoral response to SRBC results in an increased number of splenocytes producing hemolytic anti-SRBC antibodies (PFC) and the 2-ME-resistant serum hemagglutinin titer (at a dose of 0.1 mg/kg). Bestatin (1 and 0.1 mg/kg) administered to mice five times on alternate days after cyclophosphamide injection does not change the suppressive effect of the drug regarding the number of PFC, and even causes the further decrease of the total anti-SRBC hemagglutinins at dose of 1 mg/kg on day 7 after antigen stimulation[3].
Kinase Assay	Cells are harvested, washed, and lysed in NP-40 lysis buffer (50 mM Tris-HCl [pH 7.5], 150 mM NaCl, 0.5% NP-40). Total cell protein is quantified using the Bradford assay and 1-mg/mL protein aliquots are made. Ten microliters of total cell protein is mixed with 290 μL of substrate solution (0.1 mg/mL dithiothreitol [DTT], 0.1 mg/mL albumin, and 1 mM alanine-β-naphthylamide). Fluorometric measurements (340 nm excitation, 400 nm emission) are made after 15 and 30 min. The slope of the line between the 15- and 30-min measurements is used to represent aminopeptidase activity. Total cell protein is preincubated with bestatin, amastatin, puromycin, EDTA, and/or ZnCl2 for 20 min before the fluorometric aminopeptidase assay.
Cell Assay	Growing cells (1×106 to 2×106 cells/mL) are diluted to 1.0×103 cells/mL and transferred (3 mL) into a well in a 12-well multiwell plate (2.5-cm diameter/well). Cells are treated with 0, 10, 50, 100, 300, or 600 μM Bestatin and allowed to grow at 21°C shaking at 180 rpm for 48 h. A hemocytometer is used to measure cell density after 0, 24, and 48 h.
Animal Admin	Bestatin is dissolved in PBS. The agent (doses of 10, 1, and 0.1 mg/kg) is injected i.p. to non-cyclophosphamide-treated mice, 5 or 10 times at 24-h intervals before SRBC immunization. The mice are immunized 24 h after the last dose of bestatin. Pharmacological immunosuppression is induced by a single intraperitoneal injection of cyclophosphamide administered at a dose of 350 mg/kg, 12 days before SRBC immunization. Bestatin at the doses of 1 and 0.1 mg/kg is injected to cyclophosphamide-immunosuppressed mice i.p. five times at 48-h intervals or 10 times at 24-h intervals before SRBC immunization. The first dose of bestatin is administered 24 h after cyclophosphamide, while the last dose of the drug is injected 24h before SRBC immunization.
References	[1]. Hossain A, et al. Protective effects of bestatin in the retina of streptozotocin-induced diabetic mice. Exp Eye Res. 2016 Aug;149:100-6 [2]. Qian X, et al. Inhibition of p38 MAPK Phosphorylation Is Critical for Bestatin to Enhance ATRA-Induced Cell Differentiation in Acute Promyelocytic Leukemia NB4 Cells. Am J Ther. 2016 May-Jun;23(3):e680-9. [3]. Lis M, et al. The effects of bestatin on humoral response to sheep erythrocytes in non-treated and cyclophosphamide-immunocompromised mice. Immunopharmacol Immunotoxicol. 2013 Feb;35(1):133-8 [4]. Poloz Y, et al. Bestatin inhibits cell growth, cell division, and spore cell differentiation in Dictyostelium discoideum. Eukaryot Cell. 2012 Apr;11(4):545-57

Chemical & Physical Properties

Density	1.2±0.1 g/cm3
Boiling Point	604.7±55.0 °C at 760 mmHg
Melting Point	245 °C (dec.)(lit.)
Molecular Formula	C₁₆H₂₄N₂O₄
Molecular Weight	308.373
Flash Point	319.5±31.5 °C
Exact Mass	308.173615
PSA	112.65000
LogP	2.64
Vapour Pressure	0.0±1.8 mmHg at 25°C
Index of Refraction	1.557
InChIKey	VGGGPCQERPFHOB-RDBSUJKOSA-N
SMILES	CC(C)CC(NC(=O)C(O)C(N)Cc1ccccc1)C(=O)O

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: OH2915000

CHEMICAL NAME :: L-Leucine, N-(3-amino-2-hydroxy-1-oxo-4-phenylbutyl)-, (S-(R*,S*))-

CAS REGISTRY NUMBER :: 58970-76-6

LAST UPDATED :: 199612

DATA ITEMS CITED :: 9

MOLECULAR FORMULA :: C16-H24-N2-O4

MOLECULAR WEIGHT :: 308.42

WISWESSER LINE NOTATION :: 1Y1&1YVQMVYQYZ1R

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD - Lethal dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: >2 gm/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: JJANAX Japanese Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan) V.21- 1968- Volume(issue)/page/year: 36,2971,1983

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 780 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Skin and Appendages - hair Nutritional and Gross Metabolic - weight loss or decreased weight gain

REFERENCE :: JJANAX Japanese Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan) V.21- 1968- Volume(issue)/page/year: 36,2971,1983

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 1900 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Skin and Appendages - hair Nutritional and Gross Metabolic - weight loss or decreased weight gain

REFERENCE :: JJANAX Japanese Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan) V.21- 1968- Volume(issue)/page/year: 36,2971,1983

TYPE OF TEST :: LD - Lethal dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: >4 gm/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: JJANAX Japanese Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan) V.21- 1968- Volume(issue)/page/year: 36,2971,1983

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 190 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Skin and Appendages - hair Nutritional and Gross Metabolic - weight loss or decreased weight gain

REFERENCE :: JJANAX Japanese Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan) V.21- 1968- Volume(issue)/page/year: 36,2971,1983

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 1300 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Skin and Appendages - hair Nutritional and Gross Metabolic - weight loss or decreased weight gain

REFERENCE :: JJANAX Japanese Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan) V.21- 1968- Volume(issue)/page/year: 36,2971,1983

TYPE OF TEST :: LD - Lethal dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: >1200 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: JJANAX Japanese Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan) V.21- 1968- Volume(issue)/page/year: 36,2971,1983 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 63700 mg/kg/91D-C

TOXIC EFFECTS :: Kidney, Ureter, Bladder - proteinuria

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 27,401,1984 ** REPRODUCTIVE DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 1250 mg/kg

SEX/DURATION :: female 16-20 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - extra-embryonic structures (e.g., placenta, umbilical cord) Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

REFERENCE :: HMMRA2 Hormone and Metabolic Research. (Georg Thieme Verlag, Postfach 732, D-7000 Stuttgart 1, Fed. Rep. Ger.) V.1- 1969- Volume(issue)/page/year: 21,366,1989

Safety Information

Personal Protective Equipment	Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter
Hazard Codes	Xn
Safety Phrases	S22-S24/25
RIDADR	NONH for all modes of transport
WGK Germany	3
RTECS	OH2915000

Articles26

Elastase and tryptase govern TNFα-mediated production of active chemerin by adipocytes.

PLoS ONE 7(12) , e51072, (2012)

Chemerin is a leukocyte chemoattractant and adipokine with important immune and metabolic roles. Chemerin, secreted in an inactive form prochemerin, undergoes C-terminal proteolytic cleavage to genera...

Gingipain aminopeptidase activities in Porphyromonas gingivalis.

Biol. Chem. 393(12) , 1471-6, (2012)

Bestatin, a specific inhibitor of metalloaminopeptidases,inhibits the growth of Porphyromonas gingivalis. To identify its target enzyme, a library of fluorescent substrates was used but no metalloamin...

Preparation and evaluation of a new releasable PEGylated tumor necrosis factor-α (TNF-α) conjugate for therapeutic application.

Sci. China Life Sci. 56(1) , 51-8, (2013)

To design a releasable PEGylated TNF-α (rPEG-TNF-α), a cathepsin B-sensitive dipeptide (Val-Cit moiety) was inserted into conventional PEG-modified TNF-α (PEG-TNF-α), facilitating its clinical use for...

Synonyms

BESTATIN

BENIMEX

Bestatin,UbeniMex

2-(3-Amino-2-hydroxy-4-phenyl-butyrylamino)-4-methyl-pentanoic acid

Leucine, N-(3-amino-2-hydroxy-1-oxo-4-phenylbutyl)-

nk421

MFCD00083262

N-(3-Amino-2-hydroxy-4-phenylbutanoyl)leucine

EINECS 261-529-2

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