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Bestatin

Product Name
Bestatin
CAS No.
58970-76-6
Chemical Name
Bestatin
Synonyms
UBENIMEX;nk421;BENIMEX;BESTATIN;NSC 265489;Bestatin D10;Bestatin, >=99%;Ubenimex Ubenimex;Bestatin Impurity;Bestatin free base
CBNumber
CB9324019
Molecular Formula
C16H24N2O4
Formula Weight
308.37
MOL File
58970-76-6.mol
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Bestatin Property

Melting point:
245 °C (dec.)(lit.)
alpha 
D20 -15.5° (c = 1.0 in 1N HCl)
Boiling point:
448.76°C (rough estimate)
Density 
1.0917 (rough estimate)
refractive index 
1.5800 (estimate)
storage temp. 
Keep in dark place,Sealed in dry,Room Temperature
solubility 
Aqueous Acid (Slightly, Sonicated), DMSO (Slightly, Heated)
pka
8.1, 3.1(at 25℃)
form 
Powder
color 
White
optical activity
[α]20/D 11°, c = 1 in 1 M NaOH
Water Solubility 
Soluble in water (<1 25), DMSO (2 mg/ml), methanol (5 mg/ml), 1eq. NaOH (50 mM), ethanol (<1 mg/ml at 25°C), acetic acid, aq. HCl, and alkaline solution. Insoluble in ethyl acetate, benzene, hexane, and chloroform.
Merck 
13,9910
InChIKey
VGGGPCQERPFHOB-RDBSUJKOSA-N
CAS DataBase Reference
58970-76-6(CAS DataBase Reference)
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Safety

Safety Statements 
22-24/25
WGK Germany 
3
RTECS 
OH2915000
HS Code 
29242998
Toxicity
LD50 in male, female mice, male, female rats (g/kg): 1.3, 1.9, 1.9, 2.1 s.c.; 0.19, 0.19, 0.90, 0.78 i.p.; >4.0, >4.0, >2.0, >2.0 orally (Sakakibara)
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Hazard and Precautionary Statements (GHS)

Symbol(GHS)
Signal word
Warning
Hazard statements

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P271Use only outdoors or in a well-ventilated area.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P302+P352IF ON SKIN: wash with plenty of soap and water.

P304+P340IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

P312Call a POISON CENTER or doctor/physician if you feel unwell.

P403+P233Store in a well-ventilated place. Keep container tightly closed.

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N-Bromosuccinimide Price

Sigma-Aldrich
Product number
200484-M
Product name
Bestatin - CAS 58970-76-6 - Calbiochem
Purity
Binds to cell surfaces and inhibits surface aminopeptidases, notably aminopeptidase B and leucine aminopeptidase.
Packaging
200484-10MG
Price
$195
Updated
2024/03/01
Sigma-Aldrich
Product number
200484-M
Product name
Bestatin
Purity
Binds to cell surfaces and inhibits surface aminopeptidases, notably aminopeptidase B and leucine aminopeptidase.
Packaging
200484-500MG
Price
$10260
Updated
2024/03/01
Sigma-Aldrich
Product number
200484-M
Product name
Bestatin
Purity
Binds to cell surfaces and inhibits surface aminopeptidases, notably aminopeptidase B and leucine aminopeptidase.
Packaging
200484-200MG
Price
$18700
Updated
2024/03/01
Sigma-Aldrich
Product number
482609
Product name
N-[(2S,3R)-3-Amino-2-hydroxy-4-phenylbutyryl]-L-leucine
Purity
97%
Packaging
500mg
Price
$325
Updated
2024/03/01
Sigma-Aldrich
Product number
200484-M
Product name
Bestatin
Purity
Binds to cell surfaces and inhibits surface aminopeptidases, notably aminopeptidase B and leucine aminopeptidase.
Packaging
200484-250MG
Price
$18700
Updated
2024/03/01
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Bestatin Chemical Properties,Usage,Production

Description

Bestatin is an aminopeptidase inhibitor originally isolated from S. olivoreticuli. It inhibits aminopeptidase B (IC50 = 0.05 μg/ml), aminopeptidase N (IC50 = 16.9 μM), leucine aminopeptidase (IC50 = 0.01 μg/ml), and the aminopeptidase activity of leukotriene A4 (LTA4) hydrolase (Kapp = 172 nM). It is selective for these aminopeptidases over aminopeptidase A, trypsin, chymotrypsin, elastase, papain, pepsin, and thermolysin. Bestatin inhibits the production of LTB4 in erythrocytes when used at a concentration of 70 μM. It increases the expression of Akt, inhibits proliferation, migration, and invasion, and induces autophagy and apoptosis in 5637 bladder cancer cells. Bestatin (5 and 15 mg/kg) decreases serum levels of LTB4 and reduces tumor growth in a patient-derived xenograft (PDX) mouse model of colorectal cancer.

Chemical Properties

white powder, soluble in methanol, ethanol, DMSO and other organic solvents, from Streptomyces olivoreticuli.

Originator

Inst. of Microbial Chem (Japan)

Uses

Ubenimex (also known as bestatin) is a competitive aminopeptidase B inhibitor with an IC50 of 100 mg/ml for K562 cells. Proliferation of all the cell lines except KG1 was inhibited by bestatin. P39/TSU, HL60 and U937 were highly sensitive, with 50% growth inhibitory concentration. It is useful in the treatment of non-lymphocytic leukemia. In other types of cancers ubenimex added to radiotherapy or chemotherapy following surgery significantly inmases survival time through immunopotentiation. It is being studied for use in the treatment of acute myelocytic leukemia.

Uses

Bestatin is "pseudo"-dipeptide isolated from Strepotmyces olivreticuli in 1976. Bestatin is a potent aminopeptidase B inhibitor with no carboxypeptidase activity. Bestatin acts as an immunomodulator by activating macrophages and T lymphocytes. Bestatin also exhibits good antitumour activity and is has been investigated in clinical trials.

Application

Bestatin can indirectly act on monocytes by inhibiting Aminopeptidase B, which in turn inhibits the catabolism of tuftsin. Bestatin has also been shown to inhibit Leukotriene A4 hydrolase. It can directly stimulate lymphocytes through its fixation on the cell surface. The agent has been used in multiple leukemia studies. Bestatin is an aminopeptidase inhibitor, inhibits enkephalin metabolism and leukotriene A4 hydrolase. Inhibits tumor cell proliferation.

brand name

Bestatin

General Description

Bestatin was found in the culture broth of Streptomyces olivoreticuli in 1976by Umezawa et al. in the course of screening specific enzyme inhibitors of microbial origin. It shows inhibitory activity against specific exopeptidases, e.g., aminopeptidase B and leucine aminopeptidase. However, it does not act against aminopeptidase A, carboxypeptidases A and B, or endopeptidases. Bestatin acts as a bioresponse modifier and shows antitumor activity via stimulation of immuno response in the host. In combination with cytotoxic anticancer drugs, it is now under clinical evaluation for use in cancer therapy.

Biological Activity

Aminopeptidase inhibitor (K i = 0.001-90 mM); inhibits enkephalin metabolism and leukotriene A 4 hydrolase. Inhibits tumor cell proliferation.

Safety Profile

Poison by intraperitoneal route.Moderately toxic by subcutaneous route. Experimentalreproductive effects. When heated to decomposition itemits toxic fumes of NOx.

storage

Store at +4°C

Clinical claims and research

Bestatin (ubenimex) is a potent inhibitor of aminopeptidase N and aminopeptidase B, which was isolated from a culture filtrate of Streptomyces olivoreticuli during the search for specific inhibitors of enzymes present on the membrane of eukaryotic cells. Inhibitors of aminopeptidase activity are associated with macrophage activation and differentiation, and Bestatin has shown significant therapeutic effects in several clinical trials. In one multi-institutional study, patients with acute non-lymphocytic leukemia (ANLL) were randomized to receive either Bestatin or control orally after completion of induction and consolidation therapy, and concomitant with maintenance chemotherapy. Remission duration was prolonged in the Bestatin group, although this difference did not reach statistical significance. However, OS was prolonged in the Bestatin group. Recently, a confirmatory phase III trial in ANLL was reported that extended the observation to a significant prolongation of remission. Bestatin has also shown adjuvant activity when administered to acute leukemia and CML patients who did not develop graft-versus-host disease (GVHD) within 30 days following BMT. Bestatin-treated acute leukemia patients had an increased incidence of chronic low-grade GVHD compared with the control arm and a lower relapse rate. Recently, a phase III study of resected stage 1 squamous cell lung cancer patients treated orally with either Bestatin or placebo daily for 2 years revealed that 5-year cancer-free survival was significantly greater in the Bestatin group (71%) as compared to the placebo group (62%). OS was also significantly improved, as was cancer-free survival. Recent studies in patients with nonsmall cell lung cancer (NSCLCs) suggest that it also has anti-angiogenic activity.

Mode of action

Bestatin acts as an immunomodulator by activating macrophages and T lymphocytes.

References

1. umezawa h, aoyagi t, suda h, hamada m, takeuchi t, bestatin, an inhibitor of aminopeptidase b, produced by actinomycetes, j antibiot (tokyo). 1976 jan; 29(1):97-9.2. umezawa, h., aoyagi, t., suda, h., hamada, m., and takeuchi, t. 197615. antibiotics 29, 97.3. suda, h., takita, t., aoyagi, t., and umezawa, h. (1976) j. antibiotics 29, 100.4. nakamura, h., suda, h., takita, t., aoyagi, t., umezawa, h., and iitaka, y. (1976) j. antibiotics 29, 102.5. umezawa, s., tsuchiya, t., and tatsuta, k. (1966) bull. chem. sot. japan 39, 1235. 6. barlow, c. b., and gijthrie, r. d. (1967) j. chem. sot. (c) 1194. 7. bukhari, s. t. k., guthrie, r. d., scott, a. i., and wrixon, a. d. (1970) tetrahedron 26, 3653.8. suda et al. inhibition of aminopeptidase b and leucine aminopeptidase by bestatin and its stereoisomer, archives of biochemistry and biophysics, 77, 196-200 (1976)

Bestatin Preparation Products And Raw materials

Raw materials

Preparation Products

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Bestatin Suppliers

AF Biochem Co., Ltd.
Tel
+86-028-60911900 13540204019
Email
sales@afbiochem.com
Country
China
ProdList
481
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57
Suizhou HongQi Chemical Corporation Limited
Tel
0722-3257376 13026100080
Fax
0722-3257381
Email
774811011@qq.com
Country
China
ProdList
64
Advantage
55
Zhangshu Hongyuan Biomedical Technology Co., Ltd.
Tel
19195036662
Email
335864138@qq.com
Country
China
ProdList
159
Advantage
58
Zhangshu Chenxi Biotechnology Co., Ltd
Tel
19070905030
Email
cx@chenxisw.com
Country
China
ProdList
57
Advantage
58
J & K SCIENTIFIC LTD.
Tel
010-82848833 400-666-7788
Fax
86-10-82849933
Email
jkinfo@jkchemical.com
Country
China
ProdList
96815
Advantage
76
Meryer (Shanghai) Chemical Technology Co., Ltd.
Tel
021-61259108 18621169109
Fax
86-21-61259102
Email
market03@meryer.com
Country
China
ProdList
40228
Advantage
62
3B Pharmachem (Wuhan) International Co.,Ltd.
Tel
821-50328103-801 18930552037
Fax
86-21-50328109
Email
3bsc@sina.com
Country
China
ProdList
15839
Advantage
69
Chembest Research Laboratories Limited
Tel
+86-21-20908456
Fax
021-58180499
Email
sales@BioChemBest.com
Country
China
ProdList
6005
Advantage
61
Beijing HwrkChemical Technology Co., Ltd
Tel
010-89508211 18501085097
Fax
010-89508210
Email
sales.bj@hwrkchemical.com
Country
China
ProdList
8418
Advantage
55
Energy Chemical
Tel
021-021-58432009 400-005-6266
Fax
021-58436166
Email
sales8178@energy-chemical.com
Country
China
ProdList
44688
Advantage
61
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View Lastest Price from Bestatin manufacturers

Hebei Yanxi Chemical Co., Ltd.
Product
Ubenimex 58970-76-6
Price
US $0.00/kg
Min. Order
1kg
Purity
0.99
Supply Ability
500kg
Release date
2023-10-08
Hong Kong Tiansheng New Material Trading Co., Ltd
Product
Ubenimex 58970-76-6
Price
US $46.00/KG
Min. Order
1KG
Purity
99%
Supply Ability
1 ton
Release date
2021-12-13
Hong Kong Tiansheng New Material Trading Co., Ltd
Product
Ubenimex 58970-76-6
Price
US $12.39/KG
Min. Order
1Kg/Bag
Purity
99%
Supply Ability
2tons
Release date
2021-12-27

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