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Last update 23 Jan 2025

PEPD

Last update 23 Jan 2025

Basic Info

Synonyms

imidodipeptidase, PEPD, peptidase D

+ [5]

Introduction

Dipeptidase that catalyzes the hydrolysis of dipeptides with a prolyl (Xaa-Pro) or hydroxyprolyl residue in the C-terminal position (PubMed:17081196, PubMed:35165443). The preferred dipeptide substrate is Gly-Pro, but other Xaa-Pro dipeptides, such as Ala-Pro, Met-Pro, Phe-Pro, Val-Pro and Leu-Pro, can be cleaved (PubMed:17081196). Plays an important role in collagen metabolism because the high level of iminoacids in collagen (PubMed:2925654).

Drugs associated with PEPD

CQ31

Target

PEPD x XPNPEP1

Mechanism

PEPD inhibitors [+1]

Active Org.

Memorial Sloan Kettering Cancer Center

Originator Org.

Memorial Sloan Kettering Cancer Center

Active Indication

Inflammation

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

CQ80

Target

PEPD x XPNPEP1

Mechanism

PEPD inhibitors [+1]

Active Org.

Memorial Sloan Kettering Cancer Center

Originator Org.

Memorial Sloan Kettering Cancer Center

Active Indication-

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with PEPD

100 Translational Medicine associated with PEPD

0 Patents (Medical) associated with PEPD

1,336

Literatures (Medical) associated with PEPD

01 Mar 2025·Theriogenology

Integrated analyses of transcriptomes, metabolomes, and proteomes unveil the role of FoXO signaling axis in buck semen cryopreservation

Article

Author: Zhong, Tao ; Guo, Jiazhong ; Cao, Jiaxue ; Wu, Shun ; Li, Li ; Zhan, Siyuan ; Niu, Lili ; Zhang, Hongping ; Wang, Linjie ; Chen, Guolin

Sperm cryopreservation is a complex process involving gene expression, protein synthesis, membrane stability, and metabolic adaptation. However, molecular alterations in sperm cryopreservation and the mechanisms defending against freezing damage remain poorly understood. This study investigates these changes and defense mechanisms using transcriptomics, proteomics, and metabolomics data. During sperm cryopreservation, the expression level of G protein subunit alpha i3 (GNAI3) was significantly downregulated in post-thaw sperm (P < 0.001), while matrix metallopeptidase 9 (MMP9) was upregulated compared to FS groups (P < 0.01). Additionally, interleukin 6 (IL6) expression in the CS group showed an approximate increase (P < 0.05), whereas ribosomal protein S27a (RPS27A) expression decreased markedly (P < 0.05). Other important molecules such as macrophage stimulating 1 receptor (MST1R), hypoxia-inducible factor 1 subunit alpha (HIF1A), fibroblast growth factor 8 (FGF8), CD9 molecule (CD9), peptidase D (PEPD) and terminal nucleotidyltransferase 5B (TENT5B) also exhibited significant changes in expression (P < 0.05). Moreover, the study revealed the regulatory roles of metabolites such as glucose and glutamic acid during sperm cryopreservation. The involvement of catalase (CAT) protein in antioxidant defense was also noted. The interactions among mRNAs, miRNAs, proteins, and metabolites highlight the critical role of the FoxO signaling pathway in modulating responses to freezing. Our study reveals the molecular regulatory mechanisms of sperm during cryopreservation, emphasizing the importance of the FoxO pathway and specific metabolites in response to cryo-injury. These findings provide deeper insights into the complexity of sperm cryobiology and offer practical guidance for optimizing sperm cryopreservation.

01 Feb 2025·Journal of Molecular Histology

Ameliorative effects of Edaravone against Valproic Acid-Induced kidney damage

Article

Author: Bolkent, Sehnaz ; Sancar, Serap ; Bayrak, Bertan Boran ; Cakmak, Neziha Hacihasanoglu ; Yanardag, Refiye

Valproic acid (VPA) is a well-known and increasingly documented antiepileptic drug that has been widely used in the treatment of epilepsy and/or epilepsy-related disorders. Prolonged clinical use of VPA has been reported to cause side effects such as nephrotoxicity. Edaravone (EDA) is a powerful free radical scavenger. The aim of the study was to investigate the protective effects of EDA against VPA-induced oxidative renal injury. Four experimental groups were formed by randomly assigning thirty-eight male Sprague Dawley rats. The first group, (Control Group, n = 8), consisted of healthy rats. The second group, (Group II, n = 10), comprised control rats given intraperitoneally EDA (30 mg/kg/day) for seven days. The third group (Group III, n = 10) was administered intraperitoneally only VPA (500 mg/kg/day) for seven days. The last group (Group IV, n = 10) was treated with VPA + EDA for seven days. On the 8th day, kidney tissues were immediately removed from rats. In kidney homogenates, reduced glutathione levels and Na/K⁺-ATPase, paraoxonase1 and prolidase activities were remarkably decreased while catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase, myeloperoxidase, and xanthine oxidase activities and lipid peroxidation, protein carbonyl, advanced oxidized protein products, and hydroxyproline contents were notably elevated in VPA given group. Consistently, administration of EDA decreased renal degenerative changes seen in the kidney tissue of VPA given rats. Treatment with EDA in the VPA group significantly resulted in the recovery of both biochemical and histopathological alterations. As a result, EDA is potentially beneficial to revert oxidative renal damage induced by VPA.

10 Jan 2025·Journal of Clinical Oncology

Minimally Invasive Assessment of Peripheral Residual Disease During Maintenance or Observation in Transplant-Eligible Patients With Multiple Myeloma

Article

Author: Lahuerta, Juan Jose ; Cabrera, Carmen ; San-Miguel, Jesus ; Méndez, José Ángel ; Cabezudo, Elena ; Rios, Rafael ; Carrillo, Estrella ; Granell, Miquel ; Gutiérrez, Xabier ; Sureda, Ana María ; Blanchard, Mª Jesús ; Puente, María ; Riaza, Rosalía ; Casanova, María ; Notarfranchi, Laura ; Hernandez, Miguel-Teodoro ; Nájera, Mª José ; Escoda, Lourdes ; Bravo, Pilar ; Giménez, Eugenio ; Mateos, Maria-Victoria ; Hernández, José Ángel ; Burgos, Leire ; González, Marta Sonia ; Dios, Ana ; Martínez, Carmen ; Blade, Joan ; Labrador, Jorge ; Casado, Luís Felipe ; Soler, Juan Alfonso ; Monreal, Eugenia ; Palomera, Luis ; Aguilar, Carlos ; Martinez-Lopez, Joaquin ; Cedena, Maria Teresa ; García, Antonio ; Rivas, Paz ; Agullo, Cristina ; Teruel, Ana Isabel ; Rosiñol, Laura ; Íñigo, Belén ; Sampol, Antonia ; Montes, Carmen ; Lasa, Marta ; de Oteyza, Jaime Pérez ; Fernández, Ángel ; Peñalver, Francisco Javier ; Suárez, Alexia ; Oriol, Albert ; Prósper, Felipe ; Gironella, Mercedes ; Ruíz, Elena ; Martinez-Martinez, Rafael ; Orfao, Alberto ; González, Ana Pilar ; Gonzalez, Carmen ; García, Aránzazu ; Mª Moraleda, Jose ; Bargay, Joan ; Paiva, Bruno ; Prieto, Elena ; Puig, Noemi ; Mª Martí, Josep ; Castro, Sergio ; Mª Arguiñano, Jose ; Alegre, Adrián ; Escalante, Fernando ; Cabañas, Valentin ; González, Esther ; De Arriba, Felipe ; del Barrio, Rebeca Iglesias ; Calasanz, Maria Jose ; Encinas, Cristina ; Ibáñez, Ángela ; de la Guía, Ana López ; Couto, Carmen ; Calle, Mª del Carmen ; de Miguel, Dunia ; Guerrero, Camila ; Jarque, Isidro ; González, Yolanda ; Santamaría, Amparo ; Krsnik, Isabel ; Perez, Jose J. ; Flores-Montero, Juan ; Romera, Marta ; Motlló, Cristina

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.In multiple myeloma (MM), measurable residual disease (MRD) is assessed in bone marrow (BM). However, less invasive evaluation of peripheral residual disease (PRD) in blood could be advantageous and less cumbersome. We investigated the prognostic value of PRD monitoring after 24 cycles of maintenance in 138 transplant-eligible patients with MM enrolled in the GEM2012MENOS65/GEM2014MAIN clinical trials. PRD was assessed using next-generation flow (NGF) and mass spectrometry (MS). Positive PRD by NGF in 16/138 (11.5%) patients was associated with a 13-fold increased risk of progression and/or death; median progression-free survival (PFS) and overall survival (OS) were 2.5 and 47 months, respectively. Considering patients' MRD status in BM as the reference, PRD detection using NGF showed positive and negative predictive values of 100% and 73%, respectively. Presence of PRD helped identifying patients at risk of imminent progression among those with positive MRD in BM. Patients with undetectable PRD according to both NGF and MS showed 2-year PFS and OS rates of 97% and 100%, respectively. In multivariate analyses including the Revised International Staging System and the complete remission status, only MRD in BM and PRD by NGF showed independent prognostic value for PFS. This study supports the use of less invasive PRD monitoring during maintenance or observation in transplant-eligible patients with MM.

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