Last update 01 Nov 2024

APB

Last update 01 Nov 2024

Basic Info

Synonyms

Aminopeptidase B, AP-B, APB

+ [4]

Introduction

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).

Drugs associated with APB

Ubenimex

Target

APB x LTA4H

Mechanism

APB inhibitors [+2]

Active Org.

Zhejiang Apeloa Kangyu Pharmaceutical Co., Ltd. [+1]

Originator Org.

Nippon Kayaku Co., Ltd.

Active Indication

Hematopoietic stem cell transplantation [+5]

Inactive Indication

Pulmonary Arterial Hypertension

Drug Highest PhaseApproved

First Approval Ctry. / Loc.

First Approval Date01 Mar 1987

Clinical Trials associated with APB

CTR20232970 / CompletedNot Applicable

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

[Translation] A single-center, randomized, open-label, single-dose, two-sequence, two-period, double-crossover bioequivalence study of ubenimex capsules (30 mg) in Chinese healthy subjects under fasting and fed conditions

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。

[Translation]

Main purpose of study: According to the relevant provisions of bioequivalence test, Nippon Kayaku Co., Ltd. is the licensee of Ubenimex Capsules (trade name: Bestatin, specification: 30mg) as the reference preparation, and the test preparation Ubenimex Capsules (specification: 30mg) produced and provided by Xi'an Wanlong Pharmaceutical Co., Ltd. are conducted on fasting and postprandial human bioequivalence tests to compare whether the absorption rate and degree of the drug in the test preparation are within the acceptable range with the reference preparation, and to evaluate the bioequivalence of the two preparations under fasting and postprandial administration conditions. Secondary purpose of study: To observe the safety of oral administration of the test preparation Ubenimex Capsules (specification: 30mg) and the reference preparation Ubenimex Capsules (trade name: Bestatin, specification: 30mg) by healthy volunteers.

Start Date11 Oct 2023

Sponsor / Collaborator

Xian Wanlong Pharmaceutical Co. Ltd.

CTR20232253 / CompletedNot Applicable

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

[Translation] Bioequivalence study of ubenimex capsules in Chinese healthy volunteers under fasting and fed conditions

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。

[Translation]

Main research purpose This study uses Ubenimex Capsules (10 mg/capsule) developed by Chengdu Yuandong Biopharmaceutical Co., Ltd. as the test preparation, and Ubenimex Capsules (10 mg/capsule, trade name: Bestatin®) produced by the original manufacturer Nippon Kayaku Co., Ltd. as the reference preparation to evaluate the bioequivalence of the test preparation and the reference preparation under fasting and postprandial administration conditions, and provide a reference basis for the registration application and clinical use of the drug. Secondary research purpose Evaluate the safety of the test preparation Ubenimex Capsules (10 mg/capsule) and the reference preparation Bestatin® (10 mg/capsule) under fasting and postprandial conditions in healthy Chinese volunteers.

Start Date13 Aug 2023

Sponsor / Collaborator

Chengdu Easton Biopharmaceuticals Co., Ltd.

JPRN-jRCT2031210707 / RecruitingPhase 2

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

Start Date04 Jan 2023

Sponsor / Collaborator-

100 Clinical Results associated with APB

100 Translational Medicine associated with APB

0 Patents (Medical) associated with APB

454

Literatures (Medical) associated with APB

28 Oct 2024·Nucleic Acids Research

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

Article

Author: 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.

24 Jun 2024·Nucleic Acids Research

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

Article

Author: 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.

01 Sep 2023·PROTEOMICS – Clinical Applications

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

Article

Author: 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.

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