Bestatin
ubenimex
CAS: 58970-76-6
Molecular Formula: C16H24N2O4
Bestatin - Names and Identifiers
| Name | ubenimex |
| Synonyms | nk421 Bestatin bestatin ubenimex UBENIMEX UbenaMix, Inobestin, NK 421 N-(3-amino-2-hydroxy-4-phenylbutanoyl)leucine N-[(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl]leucine 3-(r)-amino-2-(s)-hydroxy-4-phenylbutanoyl-(s)-leucine N-[(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl]-D-leucine N-[(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl]-L-leucine L-Leucine,N-[(2S,3R)-3-aMino-2-hydroxy-1-oxo-4-phenylbutyl]- n-(3-amino-2-hydroxy-1-oxo-4-phenylbutyl)-,(s-(r*,s*))-l-leucin |
| CAS | 58970-76-6 |
| EINECS | 261-529-2 |
| InChI | 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 |
| InChIKey | VGGGPCQERPFHOB-RDBSUJKOSA-N |
Bestatin - Physico-chemical Properties
| Molecular Formula | C16H24N2O4 |
| Molar Mass | 308.37 |
| Density | 1.0917 (rough estimate) |
| Melting Point | 245°C (dec.)(lit.) |
| Boling Point | 448.76°C (rough estimate) |
| Specific Rotation(α) | D20 -15.5° (c = 1.0 in 1N HCl) |
| Flash Point | 319.5°C |
| 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, a |
| Solubility | DMSO : 8.33 mg/mL (27.01 mM; Need ultrasonic) |
| Vapor Presure | 1.8E-15mmHg at 25°C |
| Appearance | White powder |
| Color | White |
| Merck | 13,9910 |
| pKa | 8.1, 3.1(at 25℃) |
| Storage Condition | Keep in dark place,Sealed in dry,Room Temperature |
| Refractive Index | 1.5800 (estimate) |
| MDL | MFCD00083262 |
| Physical and Chemical Properties | White powder, soluble in methanol, ethanol, DMSO and other organic solvents, derived from Streptomyces. |
| In vitro study | Bestatin inhibits the proliferation of all human leukemia cell lines except kg1. In U937 cells, Bestatin induced DNA fragmentation and DNA ladder and enhanced caspase-3 activity. Bestatin dose-dependently induced DNA fragmentation in human leukemia cell lines. Bestatin dose-dependently inhibited the invasion of SN12M cells into the recombinant basement membrane (Matrigel). Bestatin concentration-dependently inhibits the degeneration of type IV collagen by tumor cells, but not by tumor conditioned medium (TCM). In SN12M cells, Bestatin inhibits substrate hydrolysis activity towards aminopeptidase. Bestatin inhibits tubular formation in human umbilical vein endothelial cells (HUVECs). Bestatin exerts a direct stimulating effect on lymphocytes (and monocytes) through the immobilization of leucine aminopeptidase on the cell surface, by aminopeptidase B inhibits the catabolism of phagocytic hormones exert an indirect effect on monocytes (lymphocytes). |
| In vivo study | Bestatin significantly inhibited mouse dorsal balloon assay melanoma cell-induced angiogenesis. Bestatin reduced the number of established primary tumor mass vessels in the dorsal side of mice seeded with B16-BL6 melanoma cells. In the esophageal tissue of EGDA rats, Bestatin statistically Significantly Inhibited Leukotriene B4 biosynthesis, and in EGDA rats, Bestatin reduced EAC by Incidence Rate, from 57.7% to 26.1%. |
Bestatin - Risk and Safety
| Safety Description | S22 - Do not breathe dust. S24/25 - Avoid contact with skin and eyes. |
| 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) |
Bestatin - Standard
Authoritative Data Verified Data
This product is JV-[(2S,3R)-3-amino-2-hydroxy-4-phenylbutyryl] -L-leucine. Calculated as dried product, including C16H24N204 shall not be less than 98.5%.
Last Update：2024-01-02 23:10:35
Bestatin - Trait
Authoritative Data Verified Data
- This product is white crystalline powder; Odorless.
- This product is slightly soluble in water or methanol; Soluble in glacial acetic acid, dissolved in 0.lmol/L hydrochloric acid solution or 0.lmol/L sodium hydroxide solution.
specific rotation
take this product, precision weighing, add 0.1 mol/L hydrochloric acid solution was dissolved and quantitatively diluted to prepare a solution containing about 10mg per 1ml, which was measured according to law (General rule 0621), and the specific rotation was from 15.0 ° to 18.0 °.
Last Update：2022-01-01 11:32:51
Bestatin - Differential diagnosis
Authoritative Data Verified Data
- take about 5mg of this product, add 0.5ml of 1 mol/L sodium hydroxide solution and 1 drop of copper sulfate solution, and show dark blue.
- take about 10mg of this product, add 2ml of 20% acetic acid solution, 5mg of Trione and 2 drops of 1 mol/L sodium hydroxide solution, and heat, the solution gradually appears blue-purple.
- take this product and ubenimex reference, with 30% acetic acid solution were dissolved into each 1ml containing 1 mg of test solution and reference solution, according to the related substances under the chromatographic conditions test, the retention time of the main peak of the test solution should be consistent with the retention time of the main peak of the control solution.
- The infrared absorption spectrum of this product should be consistent with that of the control (Spectrum set 911).
Last Update：2022-01-01 11:32:51
Bestatin - Exam
Authoritative Data Verified Data
acidity
take 0.25g of this product, add 25ml of water, shake, filter, take the filtrate, according to the law (General 0631),pH value should be 4.5~7.0.
Related substances
take this product, add 30% acetic acid solution to dissolve and dilute to make a solution containing about 10mg per lml as a test solution; Take an appropriate amount for precision measurement, quantitative dilution with 30% acetic acid solution was made to contain 0.1 mg solution, as a control solution. Test according to high performance liquid chromatography (General 0512). Silica gel bonded with eighteen alkyl silane was used as filler; Methanol-0.6% sodium dihydrogen phosphate solution (45:55) was used as mobile phase, column temperature was 40°C; Detection wavelength was 254nm. The number of theoretical plates shall not be less than 2500 based on ubenimex peak. 20 u1 of the test solution and the control solution were respectively injected into the human liquid chromatograph, and the chromatogram was recorded to 2 times of the retention time of the main component peak. If there are impurity peaks in the chromatogram of the test solution, the sum of each impurity peak area shall not be greater than the main peak area of the control solution (1.0%).
loss on drying
take this product, dry to constant weight at 105°C, weight loss shall not exceed 0.5% (General rule 0831).
ignition residue
take l.Og of this product and check it according to law (General rule 0841). The residue left shall not exceed 0.1%.
Heavy metals
The residue left under the item of taking the ignition residue shall not contain more than 20 parts per million of heavy metal when examined by law (General rule 0821, Law II).
Last Update：2022-01-01 11:32:52
Bestatin - Content determination
Authoritative Data Verified Data
take this product about 0.25g, precision weighing, add glacial acetic acid 30ml to dissolve, according to the potential titration method (General 0701 ), with perchloric acid titration solution (0.1 mol/L) titration, and the results of the titration were corrected with a blank test. Each 1 ml of perchloric acid titration solution (0.1 mol/L) corresponds to 30.84mg of C16H24N204.
Last Update：2022-01-01 11:32:52
Bestatin - Category
Authoritative Data Verified Data
immunomodulatory drugs, antineoplastic drugs.
Last Update：2022-01-01 11:32:53
Bestatin - Storage
Authoritative Data Verified Data
sealed storage.
Last Update：2022-01-01 11:32:53
Bestatin - Ubenimex Capsules
Authoritative Data Verified Data
This product contains ubenimex (C16N24N204) should be 90.0% to 110.0% of the label.
trait
The contents of this product are white or off-white powder or granules.
identification
- take an appropriate amount of the content of this product (about 30mg equivalent to ubenimex), add 6mL of 20% acetic acid solution, shake to dissolve ubenimex, filter, and take 2ml of the filtrate, ninhydrin 5mg and 2 drops of 1 mol/L sodium hydroxide solution were heated, and the solution became blue-purple.
- in the chromatogram recorded under the content determination item, the retention time of the main peak of the test solution should be consistent with the retention time of the main peak of the reference solution.
examination
- Content uniformity take 1 capsule (10mg specification) of this product, pour the content into a 10ml measuring flask, wash the capsule shell with 3ml methanol, wash the washing solution into the measuring flask, add an appropriate amount of 17% acetic acid solution, fully shake to dissolve ubenimex, dilute to the scale with 17% acetic acid solution, shake well, filter, take the continued filtrate, and determine the content according to the method under the content determination item, the provisions shall be met (General rule 0941).
- dissolution of this product, according to the dissolution and release determination method (General rule 0931 third method), with dilute hydrochloric acid 24ml water to ML solution lOOml(lOmg specifications) or 200ml(30mg specification) for the dissolution medium, the speed is 50 revolutions per minute, according to the operation, after 30 minutes, take the appropriate amount of solution, filtration, take the filtrate as the test solution; another ubenimex reference product was precision weighed, dissolved and quantitatively diluted with dissolution medium to make about 0 in 1 ml. 1 mg clomg specification) or 0.15mg(30mg specification) solution, as a control solution. According to the chromatographic conditions under the content determination item, 20 u1 of the test solution and the reference solution are accurately measured, and the human liquid chromatograph is injected respectively, and the chromatogram is recorded. According to the external standard method, the dissolution amount of each particle was calculated by the peak area. The limit is 80% of the labeled amount and shall be in accordance with the provisions.
- others should comply with the relevant provisions under the capsule (General 0103).
Content determination
- measured by high performance liquid chromatography (General 0512).
- chromatographic conditions and system suitability test using eighteen alkyl silane bonded silica gel as filler; Methanol-0.6% sodium dihydrogen phosphate solution (45:55) as mobile phase; Column temperature is 40°C; the detection wavelength was 254nm. The number of theoretical plates shall not be less than 2500 based on ubenimex peak.
- determine the contents under the item of loading difference, mix evenly, weigh an appropriate amount (about 50mg equivalent to ubenimex) accurately, put it in a 50ml measuring flask, and add an appropriate amount of 17% acetic acid solution, fully shake to dissolve ubenimex, dilute to the scale with 17% acetic acid solution, shake well, filter, take the continued filtrate as the test solution, and inject 20u1 into human liquid chromatograph, record the chromatogram; Take another ubenimex reference product, precisely weigh, add 17% acetic acid solution to dissolve and quantitatively dilute to make a solution containing 1 mg per 1 ml, and determine with the same method. According to the external standard method to calculate the peak area, that is.
category
Same as ubenimex.
specification
(l)10mg (2)30mg
storage
sealed storage.
Last Update：2022-01-01 11:32:54
Bestatin - Reference Information
| combination drug | due to the complexity of tumors, for some malignant tumors that are difficult to cure and easy to relapse, the curative effect of traditional treatment methods such as radiotherapy and chemotherapy is not obvious, and the combination drug strategy aimed at improving the curative effect will be the general direction of cancer treatment in the future. Ubenimesus is now combined with a variety of chemical drugs for the treatment of tumors, the effect is obvious. Recent studies have shown that ubenimesus combined with chemotherapy drugs 5-fluorouracil, doxorubicin, calcium folinate, etc. in the treatment of advanced recurrent liver cancer (especially small liver cancer with tumor diameter <3cm and 3~5cm) can enhance cell apoptosis and intracellular reactive oxygen levels, and the therapeutic effect is better than chemotherapy alone. For advanced gastric cancer, combined with S-1 combined with oxaliplatin chemotherapy, ubenimesus can reduce the serum MMP2 and MMP9 levels and enhance the anti-tumor effect. Ubenimesus can also enhance the inhibitory effect of all-trans retinoic acid on the proliferation of acute promyelocytic leukemia cells and the ability to induce cell differentiation. In addition, ubenimesus can significantly increase the inhibitory effect of cisplatin on A549 cell growth, and it may become a sensitizer for cisplatin treatment of CD13 non-small cell lung cancer. |
| indications | ubenimex is used as an immune function enhancer for adjuvant treatment of cancer chemotherapy and radiotherapy, and can be used for leukemia, multiple myeloma, myelodysplastic syndrome and hematopoietic stem cell transplantation. It is also used for other solid tumors and also for senile immunodeficiency. |
| biological activity | Bestatin (Ubenimex) is a competitive aminopeptidase B inhibitor that acts on K562 cells with an IC50 of 100 mg/ml. |
| target | TargetValue Aminopeptidase-N |
| Target | Value |
| in vitro study | Bestatin inhibit the proliferation of all human leukemia cell lines except KG1. In U937 cells, Bestatin induce DNA fragmentation and DNA ladder and enhance the activity of caspase-3. Bestati dose-dependent induction of DNA fragmentation in human leukemia cell lines. Bestatin dose-dependent inhibition of SN12M cell invasion into the recombinant basement membrane (matrix gel). Bestatin concentration-dependent inhibition of type IV collagen degeneration of tumor cells, but not through tumor-conditioned medium (TCM). In SN12M cells, the substrate hydrolysis activity towards aminopeptidase was Bestatin inhibited. Bestatin inhibits tubular formation in human umbilical vein endothelial cells (HUVECs). Bestatin exerts a direct stimulating effect on lymphocytes (and monocytes) through leucine aminopeptidase immobilized on the cell surface, and exerts an indirect effect on monocytes (lymphocytes) through aminopeptidase B inhibiting the catabolism of phagocytic hormones. |
| in vivo study | Bestatin significantly inhibit the angiogenesis induced by melanoma cells measured by the back balloon of mice. In the dorsal side of mice planted with B16-BL6 melanoma cells, the number of blood vessels in the established primary tumor mass was Bestatin reduced. In the esophageal tissue of EGDA rats, Bestatin statistically significantly inhibited the biosynthesis of leukotriene B4. In EGDA rats, the incidence of EAC was Bestatin reduced from 57.7% to 26.1%. |
| chemical properties | white powder, soluble in methanol, ethanol, DMSO and other organic solvents, derived from Streptomyces. |
| use | adjuvant treatment of acute and chronic cellular leukemia |
| category | toxic substances |
| toxicity classification | highly toxic |
| acute toxicity | abdominal cavity-rat LD50: 780 mg/kg; abdominal cavity-mouse LD50: 190 mg/kg |
| flammability hazard characteristics | combustible; Combustion produces toxic nitrogen oxide smoke |
| storage and transportation characteristics | ventilation and low temperature drying; Store separately from warehouse food raw materials |
| extinguishing agent | dry powder, foam, sand, carbon dioxide, mist water |
Last Update：2024-04-10 22:29:15
Supplier List
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Product Name: Ubenimex Visit Supplier Webpage Request for quotationCAS: 58970-76-6
Tel: 18301782025
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Multiple SpecificationsSpot supply
Product Name: Ubenimex Visit Supplier Webpage Request for quotationCAS: 58970-76-6
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
Wechat: 18301782025
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