更新于：2024-11-01

APB

更新于：2024-11-01

基本信息

别名

Aminopeptidase B、AP-B、APB

+ [4]

简介

Exopeptidase which selectively removes arginine and/or lysine residues from the N-terminus of several peptide substrates including Arg(0)-Leu-enkephalin, Arg(0)-Met-enkephalin and Arg(-1)-Lys(0)-somatostatin-14. Can hydrolyze leukotriene A4 (LTA-4) into leukotriene B4 (LTB-4) (By similarity).

关联

项与 APB 相关的药物

Ubenimex

乌苯美司

靶点

APB x LTA4H

作用机制

APB抑制剂 [+2]

在研机构

浙江普洛康裕制药有限公司 [+1]

原研机构

Nippon Kayaku Co., Ltd.

在研适应症

造血干细胞移植 [+5]

非在研适应症

肺动脉高压

最高研发阶段批准上市

首次获批国家/地区

日本

首次获批日期1987-03-01

项与 APB 相关的临床试验

CTR20232970 / CompletedN/A

乌苯美司胶囊（30mg）在中国健康受试者中空腹和餐后给药条件下、单中心、随机、开放、单剂量、两序列、两周期、双交叉生物等效性试验

主要研究目的：按有关生物等效性试验的规定，选择Nippon Kayaku Co., Ltd.为持证商的乌苯美司胶囊（商品名：Bestatin，规格：30mg）为参比制剂，对西安万隆制药股份有限公司生产并提供的受试制剂乌苯美司胶囊（规格：30mg）进行空腹和餐后给药人体生物等效性试验，比较受试制剂中药物的吸收速度和吸收程度与参比制剂的差异是否在可接受的范围内，评估两种制剂在空腹和餐后给药条件下的生物等效性。次要研究目的：观察健康志愿受试者口服受试制剂乌苯美司胶囊（规格：30mg）和参比制剂乌苯美司胶囊（商品名：Bestatin，规格：30mg）的安全性。

开始日期2023-10-11

申办/合作机构

西安万隆制药股份有限公司

CTR20232253 / CompletedN/A

乌苯美司胶囊在中国健康志愿者空腹及餐后给药条件下生物等效性试验

主要研究目的本研究以成都苑东生物制药股份有限公司研制的乌苯美司胶囊（10mg/粒）为受试制剂，原研厂家日本化药株式会社生产的乌苯美司胶囊（10mg/粒，商品名：Bestatin®）为参比制剂，评估受试制剂和参比制剂在空腹和餐后给药状态下的生物等效性，为该药注册申报及临床用药提供参考依据。次要研究目的评价中国健康志愿者空腹和餐后条件下受试制剂乌苯美司胶囊（10mg/粒）和参比制剂Bestatin®（10mg/粒）安全性。

开始日期2023-08-13

申办/合作机构

成都苑东生物制药股份有限公司

JPRN-jRCT2031210707 / Recruiting临床2期

Phase II Trial of Ubenimex Combined with Pembrolizumab + nab-Paclitaxel + Carboplatin for Untreated Patients with Advanced Squamous Non-Small Cell Lung Cancer: (UBE-Q) - UBE-Q

开始日期2023-01-04

申办/合作机构-

100 项与 APB 相关的临床结果

登录后查看更多信息

100 项与 APB 相关的转化医学

登录后查看更多信息

0 项与 APB 相关的专利（医药）

登录后查看更多信息

454

项与 APB 相关的文献（医药）

2024-10-28·Nucleic Acids Research

Polyubiquitinated PCNA triggers SLX4-mediated break-induced replication in alternative lengthening of telomeres (ALT) cancer cells

Article

作者: Park, Su Hyung ; Myung, Kyungjae ; Kim, Sangin ; Kang, Nalae ; Ra, Jae Sun ; Lee, Kyoo-young

AbstractReplication stresses are the major source of break-induced replication (BIR). Here, we show that in alternative lengthening of telomeres (ALT) cells, replication stress-induced polyubiquitinated proliferating cell nuclear antigen (PCNA) (polyUb-PCNA) triggers BIR at telomeres and the common fragile site (CFS). Consistently, depleting RAD18, a PCNA ubiquitinating enzyme, reduces the occurrence of ALT-associated promyelocytic leukemia (PML) bodies (APBs) and mitotic DNA synthesis at telomeres and CFS, both of which are mediated by BIR. In contrast, inhibiting ubiquitin-specific protease 1 (USP1), an Ub-PCNA deubiquitinating enzyme, results in an increase in the above phenotypes in a RAD18- and UBE2N (the PCNA polyubiquitinating enzyme)-dependent manner. Furthermore, deficiency of ATAD5, which facilitates USP1 activity and unloads PCNAs, augments recombination-associated phenotypes. Mechanistically, telomeric polyUb-PCNA accumulates SLX4, a nuclease scaffold, at telomeres through its ubiquitin-binding domain and increases telomere damage. Consistently, APB increase induced by Ub-PCNA depends on SLX4 and structure-specific endonucleases. Taken together, our results identified the polyUb-PCNA-SLX4 axis as a trigger for directing BIR.

2024-06-24·Nucleic Acids Research

Orphan nuclear receptors-induced ALT-associated PML bodies are targets for ALT inhibition

Article

作者: Boudier, Thomas ; Tzeng, Wan-Yi ; Shen, Yi-Ling ; Tsai, Chia-Tsen ; Joseph, Nithila A ; Chen, Liuh-Yow ; Gaela, Venus Marie ; Hsia, Hsuan-Yu ; Ting, Pin-Chao

AbstractOrphan nuclear receptors (NRs), such as COUP-TF1, COUP-TF2, EAR2, TR2 and TR4, are implicated in telomerase-negative cancers that maintain their telomeres through the alternative lengthening of telomeres (ALT) mechanism. However, how telomere association of orphan NRs is involved in ALT activation remains unclear. Here, we demonstrate that telomeric tethering of orphan NRs in human fibroblasts initiates formation of ALT-associated PML bodies (APBs) and features of ALT activity, including ALT telomere DNA synthesis, telomere sister chromatid exchange, and telomeric C-circle generation, suggesting de novo ALT induction. Overexpression of orphan NRs exacerbates ALT phenotypes in ALT cells, while their depletion limits ALT. Orphan NRs initiate ALT via the zinc finger protein 827, suggesting the involvement of chromatin structure alterations for ALT activation. Furthermore, we found that orphan NRs and deficiency of the ALT suppressor ATRX-DAXX complex operate in concert to promote ALT activation. Moreover, PML depletion by gene knockout or arsenic trioxide treatment inhibited ALT induction in fibroblasts and ALT cancer cells, suggesting that APB formation underlies the orphan NR-induced ALT activation. Importantly, arsenic trioxide administration abolished APB formation and features of ALT activity in ALT cancer cell line-derived mouse xenografts, suggesting its potential for further therapeutic development to treat ALT cancers.

2023-09-01·PROTEOMICS – Clinical Applications

Quantitative proteomic analysis of bronchoalveolar lavage fluids from patients with small cell lung cancers

Article

作者: Do, Yeji ; Vu, Hung M. ; Lee, Seung Hyeun ; Lee, Jun Hyung ; Sung, Ji‐Youn ; Nguyen, Thy N. C. ; Mohammad, Hazara Begum ; Kim, Min‐Sik

AbstractPurposeSmall cell lung cancer (SCLC) is one of the malignant cancers with aggressive progression and poor prognosis. Bronchoalveolar lavage fluid (BALF) has been arising recently as a potential source of biomarkers for lung cancers. In this study, we performed quantitative BALF proteomic analysis to identify potential biomarkers for SCLC.Experimental designBALF were collected from tumor‐bearing lungs and non‐tumor lungs of five SCLC patients. Then, BALF proteomes were prepared for a TMT‐based quantitative mass spectrometry analysis. Differentially expressed proteins (DEP) were identified when considering individual variation. Potential SCLC biomarker candidates were validated by immunohistochemistry (IHC). A public database of multiple SCLC cell lines was used to evaluate the correlation of these markers with SCLC subtypes and chemo‐drug responses.ResultsWe identified 460 BALF proteins in SCLC patients and observed considerable individual variation among the patients. Immunohistochemical analysis and bioinformatics resulted in the identification of CNDP2 and RNPEP as potential subtype markers for ASCL1 and NEUROD1, respectively. In addition, CNDP2 was found to be positively correlated with responses to etoposide, carboplatin, and irinotecan.Conclusions and clinical relevanceBALF is an emerging source of biomarkers, making it useful for the diagnosis and prognosis of lung cancers. We characterized the proteomes of paired BALF samples collected from tumor‐bearing and non‐tumor lungs of SCLC patients. Several proteins were found elevated in tumor‐bearing BALF, and especially CNDP2 and RNPEP appeared to be potential indicators for ASLC1‐high and NEUROD1‐high subtypes of SCLC, respectively. The positive correlation of CNDP2 with chemo‐drug responses would help to make decisions for treatment of SCLC patients. These putative biomarkers could be comprehensively investigated for a clinical use towards precision medicine.