Design of drug-like hepsin inhibitors against prostate cancer and kidney stones

Hepsin, a transmembrane serine protease abundant in renal endothelial cells, is a promising therapeutic target against several cancers, particularly prostate cancer. It is involved in the release and polymerization of uromodulin in the urine, which plays a role in kidney stone formation. In this work, we design new potential hepsin inhibitors for high activity, improved specificity towards hepsin, and promising ADMET properties. The ligands were developed through a novel hierarchical pipeline. This pipeline explicitly accounts for off-target binding to the related serine proteases matriptase and HGFA (human hepatocyte growth factor activator). We completed the pipeline incorporating ADMET properties of the candidate inhibitors into custom multi-objective optimization functions. The ligands designed show excellent prospects for targeting hepsin the blood stream and the urine and thus enable key experimental studies. The computational pipeline proposed is remarkably cost-efficient and can be easily adapted for designing inhibitors against new drug targets.

Clinical pathology significance of Hepsin in breast infiltrating ductal carcinoma / 实用肿瘤学杂志

Objective To investigate the expression of hepsin and its role in the pathogenesis of breast infiltrating ductal cancer ( BIDC) .Methods The expression level of hepsin was examined by immunobloting and immunohistochemistry in breast tissue samples from 8 healthy controls and 139 patients with BIDC,respectively. The correlation between hepsin level and its significance in clinical pathology of BIDC was assessed by statistical analysis.Results High level of hepsin was detected in nearly 70.5 percent of BIDC samples(98 out of 139)by immunobloting and immunohistochemistry , while the level of hepsin was relatively low or hardly detectable in healthy controls.In addition,there was a significant correlation between hepsin level and clinical stages as well as the level of histological differentiation of BIDC .Conclusion Increased expression of hepsin might play an impor-tant role in pathogenesis and progression of BIDC .The level of hepsin is positively correlated to clinical stages of BIDC,but negatively correlated with the level of histological differentiation of BIDC .

Hepsin immunohistochemical expression in prostate cancer in relation to Gleason's grade and serum prostate specific antigen.

Background: Hepsin (HPN), a type II trans-membrane serine protease, has been reported to be one of the most up regulated genes in prostate cancer. The aim of the present study was to find out immuno-histochemistry based phenotypic expression of HPN in formalin fixed paraffin embedded sections of prostate cancer compared with that in benign prostatic hyperplasia, in a prospective clinical setting, to know the differential status of HPN expression in benign and malignant prostatic disease. Materials and Methods: Tissue biopsies of histologically proven cases of prostatic cancers (48), benign prostatic hyperplasia (42), benign prostatic hyperplasia with prostatic intraepithelial neoplasia (7) and 4 cases of benign prostatic hyperplasia with prostatitis, were subjected to immunohistochemical staining with HPN antibody by strepavidin biotin method. Results: Hepsin expression was 100% in prostate carcinoma, 11.9% (5/42) in benign prostatic hyperplasia, 57.14% (4/7) in benign prostatic hyperplasia with prostatic intraepithelial neoplasia (PIN), and none in benign prostatic hyperplasia with prostatitis. Hepsin staining showe higher expression in high grade tumor in comparison to low grade tumor. Conclusions: Positive immunohistochemical expression of hepsin in cent percent cases of prostate cancer cases is intriguing, underscoring the significance of hepsin gene expression in prostate cancer.

Research of Hepsin in prostate cancer / 国际肿瘤学杂志

Hepsin is a type Ⅱ transmembrane serine protease and it' s over expressed in the majority of human prostate cancers. It has a close association with the invasion and metastasis of prostate cancer. In this paper, we review the research of Hepsin in prostate cancer.

Expression and Significance of Differential Expression Gene Hepsin in the Prostate Cancer / 中国康复理论与实践

@#Objective To evaluate the expression and significance of differential expression gene Hepsin in the prostate cancer (PC) screened by the cDNA microarray technique.Methods The techniques of semiquantitative RT-PCR and Western blotting were used to detect the mRNA and protein expression of Hepsin. Specimens of 40 cases of PC, 15 benign prostatic hyperplasia (BPH) and 6 normal prostate tissues were examined by the immunohistochemical stain.Results Hepsin was more expressed in PC tissue than normal prostate tissue (P=0.026) and was confirmed by Western blot analysis. Immunohistochemical test confirmed this and demonstrated that Hepsin did not expressed in normal prostate but expressed in PC and BPH and there was a significant difference in Hepsin expression level between PC and BPH tissues ( P=0.000).Conclusion Hepsin high expressed in PC may be a new molecular marker in early diagnosis of PC and a new target for gene therapy of PC.