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効能
抗悪性腫瘍薬, プロテアソーム阻害薬
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商品名
カイプロリス (小野薬品工業)
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説明
In July 2012, the US FDA approved carfilzomib (also referred to as PR-171) for the treatment of patients with multiple myeloma (MM) who have received at least two prior therapies including bortezomib and an immunomodulatory agent and have demonstrated disease progression within 60 days of completion of the last therapy. Carfilzomib binds to and irreversibly inhibits the chymotrypsin-like protease activity of the constitutive proteosome (β5) and immunoproteosome (β5i) via its epoxyketone pharmacophore. Proteosome inhibition results in the accumulation of polyubiquitinated proteins and induction of apoptosis through activation of both the intrinsic and extrinsic caspase pathways. Carfilzomib inhibits chymotrypsin activity with an IC50 of 6 nM and is less potent an inhibitor of trypsin and caspase (IC50s of 3600 and 2400 nM, respectively). Cell cycle arrest and apoptosis are seen in a variety of hematologic and solid tumor cell lines (e.g.,MM, acutemyeloid leukemia (AML), pancreatic cancer, lung cancer) treated with carfilzomib.
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化学的特性
White Solid
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使用
Carfilzomib is a second-generation proteasome inhibitor that is used as a treatment in relapsed and refractory multiple myeloma.
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定義
ChEBI: Carfilzomib is a synthetic tetrapeptide consisting of morpholin-4-acetyl, L-2-amino-4-phenylbutanoyl, L-leucyl and L-phenylalanyl residues joined in sequence with the C-terminus connected to the amino group of (2<element S)-2-amino-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-1-one via an amide linkage. Used for the treatment of patients with multiple myeloma.
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臨床応用
Carfilzomib is an irreversible inhibitor of the chymotrypsin-like protease in the proteasome and was
approved in the U.S. for the treatment of multiple myeloma. Carfilzomib was discovered by
Proteolix which was later acquired by Onyx Therapeutics who completed the development of this drug.
Carfilzomib is also undergoing clinical evaluation for additional oncology indications such as relapsed
solid tumors, lymphoma, prolymphocytic leukemia, acute myeloid leukemia and acute lymphocytic leukemia.
