Therapeutic Use of Carboxypeptidase G2 (CPG2)
Drugs and toxins, such as methotrexate (MTX), can accumulate in the body due to reduced ingestion or renal clearance. MTX has been shown to be effective in the management of various of diseases, including rheumatoid arthritis, psoriasis and malignancies. While high doses of MTX can cause serious side effects like pulmonary toxicity, nephrotoxicity, hepatotoxicity, hematological toxicity, and an increased risk of infections.
Carboxypeptidase G2 (CPG2) has been developed as a therapeutic enzyme because of its ability to convert MTX into non-toxic metabolites. A recombinant carboxypeptidase, generically called glucarpidase and branded as Voraxaze, was approved by FDA in 2012 to reduce toxic plasma methotrexate concentration.
Glucarpidase (Voraxaze) is a Pseudomonas sp. strain RS-16 derived carboxypeptidase, and the recombinant form of it is a homodimer protein consisting of 390 amino acids with a molecular weight of 83 kDa. Glucarpidase is produced using recombinant DNA technology in genetically engineered Escherichia coli (E. coli). Glycopeptidase catalyzes folates and folate analogs (including methotrexate, MTX) at the terminal glutamate residues, and hydrolyzes methotrexate into the inactive metabolites glutamate, 2,4-diamino-N10-methylpteroic acid (DAMPA), and 7-hydroxy-DAMPA. These inactive metabolites are cleared by the liver. Glucuronidase (Voraxaze) was developed by BTG International.
In addition, the conjugation protein of CPG2 and antibody fragments F(ab')2 or scFv against specific tumour antigens and the related prodrugs treatments for tumor-targeted drug delivery by the antibody-directed enzyme therapies (ADEPT) have been reported.
Yaohai Bio-Pharma Offers One-Stop CDMO Solution for Carboxypeptidase G2
Carboxypeptidase G2 Pipeline
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Generic name
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Brand Name/Altermative name
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Expression System
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Indications
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Manufacturer
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Latest stage
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Glucarpidase
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Voraxaze, Carboxypeptidase G2, CPG-2, OP-07, Megludase, メグルダーゼ
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E. coli
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Patients with delayed methotrexate (MTX) clearance due to impaired renal function, Drug toxicity
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BTG International, Ohara Pharmaceutical.
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Approval
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Recombinant glucarpidase G2
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Pending Update
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E. coli
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Patients with delayed MTX clearance due to impaired renal function, Drug toxicity
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Chongqing Kerun Biomedical R&D
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Phase II/III
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antibody-directed enzyme-prodrug therapy，ADEPT
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MFECP1, MFE-23:CPG2, antibody and CPG2 conjugation
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Pending Update
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Tumor, cancer
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Cancer Research UK
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Phase I
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gene-directed enzyme-prodrug therapy，GDEPT
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adenoviral methioninase gene therapy/selenomethionine GDEPT
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Pending Update
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Tumor, cancer
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AntiCancer, Inc.
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Pre-clinical
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