Request Demo

Last update 08 May 2025

ADAM17 x ADAM10

Last update 08 May 2025

Basic Info

Related Targets

ADAM17ADAM10

Drugs associated with ADAM17 x ADAM10

Aderbasib

Target

ADAM10 x ADAM17

Mechanism

ADAM10 inhibitors [+1]

Active Org.-

Originator Org.

Incyte Corp.

Active Indication-

Inactive Indication

Hematologic Neoplasms [+2]

Drug Highest PhaseDiscontinued

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with ADAM17 x ADAM10

NCT04295759

/ CompletedPhase 1IIT

A Phase I Study of the Adam-10 Inhibitor, INCB7839 in Children With Recurrent/Progressive High-Grade Gliomas to Target Microenvironmental Neuroligin-3

This is a multicenter phase 1 trial of INCB7839 for children with recurrent or progressive high-grade gliomas, including, but not limited to, diffuse intrinsic pontine glioma (DIPG) and other diffuse midline gliomas (DMGs), after upfront therapy.

Start Date27 Jul 2020

Sponsor / Collaborator

National Cancer Institute

NCT02141451

/ CompletedPhase 1/2IIT

Study of the ADAM17 Inhibitor INCB7839 Combined With Rituximab After Autologous Hematopoietic Cell Transplantation (HCT) For Patients With Diffuse Large B Cell Non-Hodgkin Lymphoma (DLBCL)

This is a single institution phase I/II study using an ADAM17 inhibitor (INCB7839) with rituximab as consolidation therapy after an autologous hematopoietic cell transplant (HCT) for patients with diffuse large B cell lymphoma (DLBCL). The study consists of two phases. The dose finding phase is a modified version of a phase I trial and the extended phase is a modified version of a phase II trial.

Start Date01 May 2014

Sponsor / Collaborator

University of Minnesota Masonic Cancer Center

NCT01254136

/ TerminatedPhase 1/2

A Phase I/II Study to Assess the Safety and Therapeutic Effect of INCB007839 in Combination With Trastuzumab and Vinorelbine in Patients With Metastatic HER2+ Breast Cancer.

This Phase I/II study is designed to assess the safety and therapeutic effect of INCB007839 in combination with trastuzumab and vinorelbine in patients with metastatic HER2+ breast cancer.

Start Date01 Oct 2010

Sponsor / Collaborator

Incyte Corp.

100 Clinical Results associated with ADAM17 x ADAM10

100 Translational Medicine associated with ADAM17 x ADAM10

0 Patents (Medical) associated with ADAM17 x ADAM10

514

Literatures (Medical) associated with ADAM17 x ADAM10

01 Jun 2025·Life Science Alliance

Antibodies targeting ADAM17 reverse neurite outgrowth inhibition by myelin-associated inhibitors

Article

Author: Chan, Eric ; Nikolov, Dimitar B ; Mendoza, Rachelle P ; Tipping, Murray J ; Romin, Yevgeniy ; Saha, Nayanendu

Upon spinal cord injury, axons attempting to regenerate need to overcome the repulsive actions of myelin-associated inhibitors, including the myelin-associated glycoprotein, Nogo-A, and the oligodendrocyte myelin glycoprotein. These inhibitors bind and signal through a neuronal receptor/co-receptor/transducer complex composed of NgR1, Lingo-1, and p75. Consequently, p75 is cleaved by alpha secretase followed by gamma-secretase, triggering downstream signaling that inhibits axonal regrowth. ADAM10 and ADAM17 are both known to function as alpha secretases in neurons. Here we show that ADAM17, and not ADAM10, is the alpha secretase that recognizes and cleaves p75, when it is a part of a 5-component neuron-myelin signaling complex comprising NgR1, Lingo-1, p75, GT1b, and a myelin inhibitor. Importantly, we demonstrate the ability of inhibitory anti-ADAM17 mAbs to abrogate the cleavage of p75 in a neuroblastoma-glioma cell line and reverse the neurite outgrowth inhibition by myelin-associated inhibitors.

01 Apr 2025·Immunology

IL‐6 Signalling to Responding T Cells Is Key to Calcitonin Gene‐Related Peptide‐Exposed Endothelial Cell Enhancement of Th17 Immunity During Langerhans Cell Antigen Presentation

Article

Author: Stohl, Lori L. ; Wagner, John A. ; Ding, Wanhong ; Granstein, Richard D. ; Moattari, Cameron ; Zhou, Xi K.

ABSTRACTCalcitonin gene‐related peptide (CGRP) biases Langerhans cell (LC) Ag presentation to CD4+ T cells towards Th17‐type immunity through actions on endothelial cells (ECs). We now report further evidence that IL‐6 signalling at responding T cells mediates this effect. This CGRP effect was absent with ECs from IL‐6 KO mice. Exposure of LCs, but not T cells, to IL‐6 enhanced IL‐6 and IL‐17A production and reduced IFN‐γ in the T‐cell response. Pretreatment of LCs with IL‐6 receptor α‐chain (IL‐6Rα) antibodies prior to IL‐6 exposure significantly inhibited these responses. However, T‐cell pretreatment with an IL‐6/IL‐6Rα chimera mimicked the effect of IL‐6 pretreatment of LCs on T‐cell responses. When this experiment was performed in the presence of the ADAM17 and ADAM10 inhibitor TAPI‐1 during LC pretreatment of LCs and during the Ag presentation culture, release of soluble IL‐6Rα chains into the medium was very significantly reduced, but this did not affect levels of T‐cell cytokine release. Interestingly, LC exposure to IL‐6 significantly increased LC IL‐6 expression. Furthermore, pretreatment of T cells with antibodies against the IL‐6 receptor β‐chain significantly inhibited the IL‐6 effect. CGRP may stimulate ECs in lymphatics and/or lymph nodes to produce IL‐6 which likely results in migrating LCs nonclassically presenting IL‐6. Furthermore, we found that IL‐6 induces IL‐6 production by LCs, suggesting an autocrine amplification pathway for this effect.

03 Feb 2025·Journal of Clinical Investigation

Metalloproteinase inhibitors regulate biliary progenitor cells through sDLK1 in organoid models of liver injury

Article

Author: Tharmapalan, Pirashaanthy ; Sanchez, Otto ; Aliar, Kazeera ; Saw, Sanjay ; Fang, Hui ; Shetty, Ronak ; Khokha, Rama ; Vyas, Foram ; Knox, Jennifer J ; Sarkar, Soumili ; Waterhouse, Paul D ; Reddy Narala, Swami ; Defamie, Virginie

Understanding cell fate regulation in the liver is necessary to advance cell therapies for hepatic disease. Liver progenitor cells (LPCs) contribute to tissue regeneration after severe hepatic injury, yet signals instructing progenitor cell dynamics and fate are largely unknown. Tissue inhibitor of metalloproteinases 1 (TIMP1) and TIMP3 control the sheddases ADAM10 and ADAM17, key for NOTCH activation. Here we uncover the role of the TIMP/ADAM/NOTCH/DLK1 axis in LPC maintenance and cholangiocyte specification. Combined TIMP1/TIMP3 loss in vivo caused abnormal portal triad stoichiometry accompanied by collagen deposits, dysregulated Notch signaling, and increased soluble DLK1. The MIC1-1C3+CD133+CD26- biliary progenitor population was reduced following acute CCl4 or chronic DDC liver injury and in aged TIMP-deficient livers. Single-cell RNA sequencing data interrogation and RNAscope identified portal mesenchymal cells coexpressing ADAM17/DLK1 as enzymatically equipped to process DLK1 and direct LPC differentiation. Specifically, TIMP-deficient biliary fragment-derived organoids displayed increased propensity for cholangiocyte differentiation. ADAM17 inhibition reduced Sox9-mediated cholangiocyte differentiation, prolonging organoid growth and survival, whereas WT organoids treated with soluble DLK1 triggered Sox9 expression and cholangiocyte specification in mouse and patient-derived liver organoids. Thus, metalloproteinase inhibitors regulate instructive signals for biliary cell differentiation and LPC preservation within the portal niche, providing a new basis for cell therapy strategies.

Analysis

Perform a panoramic analysis of this field.

view full example data

AI Agents Built for Biopharma Breakthroughs

Accelerate discovery. Empower decisions. Transform outcomes.

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis