Bortezomib C화학적 특성, 용도, 생산
화학적 성질
Yellow Solid
용도
Bortezomib is the first proteasome inhibitor to be approved b 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. T
정의
ChEBI: L-Phenylalaninamide substituted at the amide nitrogen by a 1-(dihydroxyboranyl)-3-methylbutyl group and at Nalpha by a pyrazin-2-ylcarbonyl group. It is a dipeptidyl boronic acid tha
reversibly inhibits the 26S proteasome.
일반 설명
Proteasomes normally function to degrade proteins that areno longer needed by the cell. Such proteins are normallymarked by the addition of ubiquitin, a 76 amino acid proteinthat is added to the -amino group of lysine residues onthe target proteins. The marked proteins are then hydrolyzedby the large barrel-shaped proteasomes to givepeptides of 7 to 8 residues that may be further hydrolyzedand reutilized by the cell. This process serves to regulateprotein levels within the cell, remove defective proteins,and becomes important in maintaining normal signal transduction.Inhibition of the proteasomes results in the buildup of ubiquitylated proteins, which disrupts cell-signalingprocesses and cell growth. The signaling bytranscription factor NF-B (nuclear factor B) appears tobe especially sensitive to bortezomib. NF-B is associatedwith the transcription of antiapoptotic and proliferativegenes but is under the control of IB (inhibitor of NF-B).IB can itself be phosphorylated by IKK (IB kinase),which marks IB for ubiquitylation and destruction allowingNF-B to mediate its antiapoptotic and proliferative effects effects.In the presence of the competitive inhibitor bortezomib(IC
50＝0.6 nM), the 26S proteasome is inhibitedand the ubiquitylated I
kB is still capable of inhibiting NF-
kB, preventing its effects.
Pharmaceutical Applications
Bortezomib belong to the class of drugs called proteasome inhibitors and is licensed in the United States and
the United Kingdom for the treatment of multiple myeloma. The drug has been licensed for patients in whom
the myeloma has progressed despite prior treatment or where a bone marrow transplant is not possible or was
not successful. It is marketed under the name Velcade? or Cytomib?. Velcade is administered via injection
and is sold as powder for reconstitution.
Bortezomib was the first drug approved in the new drug class of proteasome inhibitors and boron seems to
be its active element. For the mode of action, it is believed that the boron atom binds with high affinity and
specificity to the catalytic site of 26S proteasome and inhibits its action. Therapy with Bortezomib can lead
to a variety of adverse reactions, including peripheral neuropathy, myelosuppression, renal impairment and
gastrointestinal (GI) disturbances together with changes in taste. Nevertheless, the side effects are in most
cases less severe than with alternative treatment options such as bone marrow transplantation.
Bortezomib 준비 용품 및 원자재
원자재
준비 용품
