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Prostate-specific Membrane Antigen (PSMA)

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As a leading supplier in ADCs cytotoxin discovery and manufacture, BOC Sciences offers specific products for prostate-specific membrane antigen (PSMA). As a transmembrane glycoprotein, prostate-specific membrane antigen (PSMA) is a promising target for noninvasive detection of recurrent prostate cancer (PCa) and therapy of metastatic castration-resistant PCa (mCRPC) using PSMA-targeted agents such as radioligands. Although PSMA-targeted radiopharmaceutical therapy (RPT) has enabled significant imaging and prostate-specific antigen (PSA) responses, accumulating clinical data reveal its limitations, including a subgroup of non-responders, relapse, radiation-induced toxicity, and the requirement of specialized facilities for its administration. To date, non-radioactive attempts to leverage PSMA to treat PC with antibodies, nanomedicines, or cell-based therapies have met with modest success and are gaining an increasingly important role in the clinical management of PCa patients.

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More information About Prostate-specific Membrane Antigen (PSMA)

Prostate-specific Membrane Antigen (PSMA) Characteristics

Prostate-specific membrane antigen (PSMA) is the prototypic cell-surface marker of prostate cancer and is abundantly expressed in non-prostatic tumor neovasculature. The PSMA gene consists of 19 exons that span approximately 60 kb of genomic DNA and encodes a type II transmembrane protein with a short amino-terminal cytoplasmic tail (19 amino acids), a hydrophobic transmembrane domain (24 amino acids), and a large extracellular domain (707 amino acids) at the carboxy-terminus. The deduced amino acid sequence contains 10 canonical sites for N-linked glycosylation, and carbohydrate moieties are critical for PSMA function and cellular trafficking.

PSMA consists of domain I  (brown), domain II (green), and C-terminal domain (purple). Fig. 1. PSMA consists of domain I (brown), domain II (green), and C-terminal domain (purple).

Prostate-specific Membrane Antigen (PSMA) Inhibitor

PSMA antibody-drug conjugates (PSMA ADC) have demonstrated preclinical proof-of-concept. PSMA ADC comprises a fully human, dimer-specific PSMA mAb linked to monomethyl auristatin E (MMAE), a dolastatin derivative that potently inhibits tubulin polymerization. PSMA ADC incorporates a dipeptide linkage designed to maintain serum stability while maximizing intracellular drug release by human cathepsin B. PSMA ADC was evaluated for antitumor activity in vitro with mouse xenograft model of androgen-independent disease. PSMA ADC eliminated PSMA-expressing cells with picomolar potency and >700-fold selectivity in cell culture. When used to treat mice with established human C4-2 tumors, PSMA ADC significantly improved median survival 9-fold relative to controls in the absence of apparent toxicity. Treatment effects were also manifest as significant reductions in serum PSA. PSMA ADC is currently being evaluated in preclinical toxicology studies. Furthermore, vipivotide tetraxetan is a highly effective prostate-specific membrane antigen (PSMA) inhibitor, widely used in antibody-drug conjugate (ADC) development.

References:

  1. Rajasekaran, A.K.; et al.Clinical Trials of Cancer Therapies Targeting Prostate-Specific Membrane Antigen. Reviews on Recent Clinical Trials, 2007, 2: 82-190.
  2. Paller MD, C.GJ.; et al. A pilot study of prostate-pecific membrane antigen (PSMA) dynamics inmenundergoing treatment for advanced prostate cancer. The Prostate., 2019:1-7.
  3. Aminia, S.K.; et al. Potential effective inhibitory compounds against Prostate Specific Membrane Antigen (PSMA): A molecular docking and molecular dynamics study. Archives of Biochemistry and Biophysics, 2021, 699: 108747.
* Only for research. Not suitable for any diagnostic or therapeutic use.

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