SHD

Last update 23 Jan 2025

Basic Info

Synonyms

SH2 domain-containing adapter protein D, SHD, Src homology 2 domain containing transforming protein D

Introduction

May function as an adapter protein.

100 Clinical Results associated with SHD

100 Translational Medicine associated with SHD

0 Patents (Medical) associated with SHD

387

Literatures (Medical) associated with SHD

01 Jan 2025·European Journal of Medicinal Chemistry

Discovery of novel phenyl urea SHP2 inhibitors with anti-colon cancer and potential immunomodulatory effects

Article

Author: Shen, Guoqing ; Hu, Yingxin ; Wang, Tianyu ; Zhang, Kuojun ; Zhang, Xiangyu ; Guo, Jiazheng ; Wang, Kaizhen ; Jiang, Sheng

Src Homology-2 Domain Containing Protein Tyrosine Phosphatase-2 (SHP2) is a non-receptor-type protein tyrosine phosphatase (PTP), which is recognized as potential and attractive cancer therapeutic target. Currently, no SHP2 inhibitors have been approved for clinical use, and colorectal cancer (CRC) cells exhibited frequent resistance to reported SHP2 inhibitors, such as SHP099 and TNO155. Herein, we reported our discovery and optimization of phenyl urea as novel SHP2 inhibitors. A8, the most potential SHP2 inhibitor, exhibited great antiproliferative activities against SHP099/TNO155-insensitive tumor cell lines, and rescued PD-L1-mediated immunosuppression. A8 significantly suppressed in vivo tumor growth in a CT26 mouse model and activated immunomodulatory effects in tumor microenvironment. Our work demonstrated that A8 has the potential to be a lead compound for the further development of SHP2 inhibitor and the treatment of CRC.

01 Dec 2024·Cellular and Molecular Life Sciences

Re-expression of epigenetically silenced PTPRR by histone acetylation sensitizes RAS-mutant lung adenocarcinoma to SHP2 inhibition

Article

Author: Xue, Nina ; You, Shen ; Wang, Weida ; Ji, Ming ; Du, Tingting ; Hu, Xiaowen ; Hou, Zhenyan ; Chen, Xiaoguang ; Wang, Mingjin

Silenced protein tyrosine phosphatase receptor type R (PTPRR) participates in mitogen-activated protein kinase (MAPK) signaling cascades during the genesis and development of tumors. Rat sarcoma virus (Ras) genes are frequently mutated in lung adenocarcinoma, thereby resulting in hyperactivation of downstream MAPK signaling. However, the molecular mechanism manipulating the regulation and function of PTPRR in RAS-mutant lung adenocarcinoma is not known. Patient records collected from the Cancer Genome Atlas and Gene Expression Omnibus showed that silenced PTPRR was positively correlated with the prognosis. Exogenous expression of PTPRR suppressed the proliferation and migration of lung cancer cells. PTPRR expression and Src homology 2 containing protein tyrosine phosphatase 2 (SHP2) inhibition acted synergistically to control ERK1/2 phosphorylation in RAS-driven lung cancer cells. Chromatin immunoprecipitation assay revealed that HDAC inhibition induced enriched histone acetylation in the promoter region of PTPRR and recovered PTPRR transcription. The combination of the HDAC inhibitor SAHA and SHP2 inhibitor SHP099 suppressed the progression of lung cancer markedly in vitro and in vivo. Therefore, we revealed the epigenetic silencing mechanism of PTPRR and demonstrated that combination therapy targeting HDAC and SHP2 might represent a novel strategy to treat RAS-mutant lung cancer.

01 Nov 2024·EuroIntervention

Percutaneous Valvular and Structural Heart Disease Interventions.2024 Core Curriculum of the European Association of Percutaneous Cardiovascular Interventions (EAPCI) of the ESC in collaboration with the European Association of Cardiovascular Imaging (EACVI) and the Cardiovascular Surgery Working Group (WG CVS) of the European Society of Cardiology

Article

Author: Mehilli, Julinda ; Bonaros, Nikolaos ; O'Connor, Stephen ; Czerny, Martin ; Lurz, Philipp ; Ghanem, Alexander ; Agricola, Eustachio ; Veulemans, Verena ; Deharo, Pierre ; Dudek, Dariusz ; Paradies, Valeria ; Ninios, Vlasis ; Buchanan, Gill Louise ; Naber, Christopher ; De Backer, Ole ; Van Belle, Eric ; Joshi, Francis R ; Luz, Andre ; Arzamendi, Dabit ; Chieffo, Alaide ; van Mieghem, Nicolas ; Tchétché, Didier ; Ghazzal, Ziyad ; Vincent, Flavien ; Silva, Joana Delgado ; Fraccaro, Chiara ; van Wely, Marleen ; Poliacikova, Petra ; Baumbach, Andreas ; Fovino, Luca Nai ; Barbato, Emanuele ; Favero, Luca ; Nuis, Rutger-Jan ; Sondegaard, Lars ; Elbaz-Greener, Gabby ; Droogmans, Steven ; Parma, Radoslaw ; Kala, Petr ; Thiele, Holger ; Karam, Nicole ; Pilgrim, Thomas ; James, Stefan ; Mylotte, Darren ; Amat-Santos, Ignacio Jesus ; Kunadian, Vijay ; Gilard, Martine ; Hermanides, Renicus ; Schmidt, Michael Rahbek ; Silva, Bruno ; Tarantini, Giuseppe ; Uebing, Anselm ; Blackman, Daniel ; Teles, Rui Campante ; MacCarthy, Phil ; Rück, Andreas ; Thielmann, Matthias ; Donal, Erwan ; Giannini, Cristina

The percutaneous treatment of structural, valvular, and non-valvular heart disease (SHD) is rapidly evolving. The Core Curriculum (CC) proposed by the EAPCI describes the knowledge, skills, and attitudes that define competency levels required by newly trained SHD interventional cardiologists (IC) and provides guidance for training centres. SHD ICs are cardiologists who have received complete interventional cardiology training. They are multidisciplinary team specialists who manage adult SHD patients from diagnosis to follow-up and perform percutaneous procedures in this area. They are competent in interpreting advanced imaging techniques and master planning software. The SHD ICs are expected to be proficient in the aortic, mitral, and tricuspid areas. They may have selective skills in either the aortic area or mitral/tricuspid areas. In this case, they must still have common transversal competencies in the aortic, mitral, and tricuspid areas. Additional SHD domain competencies are optional. Completing dedicated SHD training, aiming for full aortic, mitral, and tricuspid competencies, requires at least 18 months. For full training in the aortic area, with basic competencies in mitral/tricuspid areas, the training can be reduced to 1 year. The same is true for training in the mitral/tricuspid area, with competencies in the aortic area. The SHD IC CC promotes excellence and homogeneous training across Europe and is the cornerstone of future certifications and patient protection. It may be a reference for future CC for national associations and other SHD specialities, including imaging and cardiac surgery.

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