[(1R)-3-methyl-1-[(2S)-3-phenyl-2-(pyrazin-2-ylformamido)propanamido]butyl]boronic acid

• ChemBase ID: 5119
• Molecular Formular: C19H25BN4O4
• Molecular Mass: 384.2372
• Monoisotopic Mass: 384.1968857
• SMILES: n1c(cncc1)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CC(C)C)B(O)O
• Canonical SMILES: CC(C[C@@H](B(O)O)NC(=O)[C@@H](NC(=O)c1cnccn1)Cc1ccccc1)C
• InChI: InChI=1S/C19H25BN4O4/c1-13(2)10-17(20(27)28)24-18(25)15(11-14-6-4-3-5-7-14)23-19(26)16-12-21-8-9-22-16/h3-9,12-13,15,17,27-28H,10-11H2,1-2H3,(H,23,26)(H,24,25)/t15-,17-/m0/s1
• InChIKey: GXJABQQUPOEUTA-RDJZCZTQSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: [(1R)-3-methyl-1-[(2S)-3-phenyl-2-(pyrazin-2-ylformamido)propanamido]butyl]boronic acid
• IUPAC Traditional name: @bortezomib; bortezomib
• Synonyms: N-[(1R)-1-(DIHYDROXYBORYL)-3-METHYLBUTYL]-N-(PYRAZIN-2-YLCARBONYL)-L-PHENYLALANINAMIDE; Velcade; MG-341; PS-341; Bortezomib; B-[(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(2-pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid; [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid; Radiciol; NSC 681239; DPBA; LDP 341; MG 341; MLN 341; PS 314; PS 341

Database IDs

• CAS Number: 179324-69-7
• PubChem SID: 99443946; 160968549
• PubChem CID: 387447

CALCULATED PROPERTIES

JChem

• Acid pKa: 13.037311
• H Acceptors: 6
• H Donor: 4
• LogD (pH = 5.5): 1.5302998
• LogD (pH = 7.4): 1.5302991
• Log P: 1.5303
• Molar Refractivity: 99.3738 cm^3
• Polarizability: 40.15836 Å^3
• Polar Surface Area: 124.44 Å^2
• Rotatable Bonds: 9
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 0.89
• LOG S: -3.86
• Solubility (Water): 5.32e-02 g/l

PROPERTIES

Physical Property

• Solubility: Chloroform; Dimethyl Sulfoxide; DMSO; Ethanol; Methanol
• Apperance: White to Off-White Solid
• Melting Point: 122-124°C

Safety Information

• Storage Condition: -20°C; Hygroscopic, -20°C Freezer, Under Inert Atmosphere

Pharmacology Properties

• Target: IGF-1R

Product Information

• Salt Data: Free Base

DETAILS

DrugBank - DB07475

Drug information: experimental

Selleck Chemicals - S1013

Research Area

• Description: Solid tumours, Non-small cell lung cancer

Protocol

• Protocol: Kinase Assay ^[1]
• Kinetic Methods: In a typical kinetic run, 2.00 mL of assay buffer (20 mM HEPES, 0.5 mM EDTA, 0.035% SDS, pH 7.8) and Suc-Leu-Leu-Val-Tyr-AMC in DMSO are added to a 3 mL fluorescence cuvette, and the cuvette is placed in the jacketed cell holder of a fluorescence spectrophotometer. Reaction temperature is maintained at 37 °C by a circulating water bath. After the reaction solution has reached thermal equilibrium (5 minutes), 1 μL?10 μL of the stock enzyme solution is added to the cuvette. Reaction progress is monitored by the increase in fluorescence emission at 440 nm (λ_ex = 380 nm) that accompanies cleavage of AMC from peptide-AMC substrates.
• Protocol: Cell Assay ^[1]
• Cell Lines: U266, IM-9, and Hs Sultan cells
• Concentrations: 0-10 μM
• Incubation Time: 48 hours
• Methods:

  The inhibitory effect of Bortezomib on MM and BMSC growth is assessed by measuring MTT dye absorbance of the cells. Cells from 48-hour cultures are pulsed with 10 μL of 5 mg/mL MTT to each well for the last 4 hour of 48-hour cultures, followed by 100 μL of isopropanol containing 0.04 N HCl. Absorbance is measured at 570 nm using a spectrophotometer.

• Protocol: Animal Study ^[2]
• Animal Models: Mice are inoculated s.c. into the right flank with RPMI 8226 MM cells.
• Formulation: Bortezomib is dissolved in 0.9% sodium chloride.
• Doses: ≤1mg/kg
• Administration: Administered via i.v.

References

• References: [1] Hideshima T, et al. Cancer Res, 2001, 61(7), 3071-3076.
• References: [2] LeBlanc R, et al. Cancer Res, 2002, 62(17), 4996-5000.
• References: [3] Yu C, et al. Blood, 2003, 102(10), 3765-3774.
• References: [4] Nie D, et al. Leuk Lymphoma, 2012.

Toronto Research Chemicals - B675700

Bortezomib is the first proteasome inhibitor to be approved by the US FDA for multiple myeloma, a blood cancer. A reversible inhibitor of the 26S proteasome-a barrel-shaped multiprotein particle found in the nucleus and cytosol of all eukaryotic cells.

REFERENCES

• Hideshima T, et al. Cancer Res, 2001, 61(7), 3071-3076.
• LeBlanc R, et al. Cancer Res, 2002, 62(17), 4996-5000.
• Yu C, et al. Blood, 2003, 102(10), 3765-3774.
• Nie D, et al. Leuk Lymphoma, 2012.
• Nawrocki, S.T., et al: Cancer Research, 65, 11510 (2005)
• Drahl C.: Chem. and Eng. News, 87, 41 (2009)