Drug General Information
Drug ID D0SH3I
Drug Name Bortezomib
Synonyms 179324-69-7; Velcade; Bortezomib (PS-341); UNII-69G8BD63PP; N-[(1R)-1-(DIHYDROXYBORYL)-3-METHYLBUTYL]-N-(PYRAZIN-2-YLCARBONYL)-L-PHENYLALANINAMIDE; MLN-341; [(1R)-3-methyl-1-[[(2S)-3-phenyl-2-(pyrazine-2-carbonylamino)propanoyl]amino]butyl]boronic acid; [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic acid; CHEMBL325041; 69G8BD63PP; Boronic acid,; DPBA; PROSCRIPT BORONIC ACID; LPD 341; LPD-341; VELCADE (TN); Velcade (TN); Pyz-Phe-boroLeu; Bortezomib(JAN/USAN/INN); Velcade, MG-341, PS-341, Bortezomib; N-[(1R)-1-(dihydroxyboranyl)-3-methylbutyl]-Nalpha-(pyrazin-2-ylcarbonyl)-L-phenylalaninamide; Bortezomib (Proteasome inhibitor); Peptide boronate
Drug Type Small molecular drug
Therapeutic Class Anticancer Agents
Company Takeda
Structure D0SH3I
Drug Resistance Mutations
Target Name Fibroblast growth factor receptor 3 (FGFR3) Target Info
Gene Name FGFR3
Uniprot ID FGFR3_HUMAN
Species Homo sapiens
Reference Sequence MGAPACALALCVAVAIVAGASSESLGTEQRVVGRAAEVPGPEPGQQEQLVFGSGDAVELS
CPPPGGGPMGPTVWVKDGTGLVPSERVLVGPQRLQVLNASHEDSGAYSCRQRLTQRVLCH
FSVRVTDAPSSGDDEDGEDEAEDTGVDTGAPYWTRPERMDKKLLAVPAANTVRFRCPAAG
NPTPSISWLKNGREFRGEHRIGGIKLRHQQWSLVMESVVPSDRGNYTCVVENKFGSIRQT
YTLDVLERSPHRPILQAGLPANQTAVLGSDVEFHCKVYSDAQPHIQWLKHVEVNGSKVGP
DGTPYVTVLKTAGANTTDKELEVLSLHNVTFEDAGEYTCLAGNSIGFSHHSAWLVVLPAE
EELVEADEAGSVYAGILSYGVGFFLFILVVAAVTLCRLRSPPKKGLGSPTVHKISRFPLK
RQVSLESNASMSSNTPLVRIARLSSGEGPTLANVSELELPADPKWELSRARLTLGKPLGE
GCFGQVVMAEAIGIDKDRAAKPVTVAVKMLKDDATDKDLSDLVSEMEMMKMIGKHKNIIN
LLGACTQGGPLYVLVEYAAKGNLREFLRARRPPGLDYSFDTCKPPEEQLTFKDLVSCAYQ
VARGMEYLASQKCIHRDLAARNVLVTEDNVMKIADFGLARDVHNLDYYKKTTNGRLPVKW
MAPEALFDRVYTHQSDVWSFGVLLWEIFTLGGSPYPGIPVEELFKLLKEGHRMDKPANCT
HDLYMIMRECWHAAPSQRPTFKQLVEDLDRVLTVTSTDEYLDLSAPFEQYSPGGQDTPSS
SSSGDDSVFAHDLLPPAPPSSGGSRT [Homo sapiens]
Targeted Disease Leukemia; Myeloma
Drug Resistance Mutations
Mutation info Missense: Y373C [1], [2]
Target Name Proteasome subunit beta type-5 (PSMB5) Target Info
Gene Name PSMB5
Uniprot ID PSB5_HUMAN
Species Homo sapiens
Reference Sequence MALASVLERPLPVNQRGFFGLGGRADLLDLGPGSLSDGLSLAAPGWGVPEEPGIEMLHGT
TTLAFKFRHGVIVAADSRATAGAYIASQTVKKVIEINPYLLGTMAGGAADCSFWERLLAR
QCRIYELRNKERISVAAASKLLANMVYQYKGMGLSMGTMICGWDKRGPGLYYVDSEGNRI
SGATFSVGSGSVYAYGVMDRGYSYDLEVEQAYDLARRAIYQATYRDAYSGGAVNLYHVRE
DGWIRVSSDNVADLHEKYSGSTP [Homo sapiens]
Targeted Disease Leukemia; Myeloma
Drug Resistance Mutations
Mutation info Missense: C52F [3]
Level of Resistance Confer 13 fold resistance
Mutation info Missense: A49T [4]
Level of Resistance Confer 66.7 fold resistance
Mutation info Missense: A49V [4]
Level of Resistance Confer 39.4 fold resistance
Mutation info Missense: A50V [4]
Level of Resistance Confer 66.7 fold resistance
References
REF 1 Bortezomib therapeutic effect is associated with expression of FGFR3 in multiple myeloma cells. Anticancer Res. 2009 Jan;29(1):1-9.
REF 2 Constitutively active FGFR3 with Lys650Glu mutation enhances bortezomib sensitivity in plasma cell malignancy. Anticancer Res. 2011 Jan;31(1):113-22.
REF 3 Anti-leukemic activity and mechanisms underlying resistance to the novel immunoproteasome inhibitor PR-924.Biochem Pharmacol.2014 May 1;89(1):43-51.
REF 4 Different mutants of PSMB5 confer varying bortezomib resistance in T lymphoblastic lymphoma/leukemia cells derived from the Jurkat cell line.Exp Hematol.2009 Jul;37(7):831-7.

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