Delving into the Latest Updates on MRX-2843 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

Mechanism

FLT3 inhibitors(Tyrosine-protein kinase receptor FLT3 inhibitors), MerTK inhibitors(Tyrosine-protein kinase Mer inhibitors)

Therapeutic Areas

NeoplasmsHemic and Lymphatic DiseasesImmune System Diseases+ [1]

Active Indication

Refractory acute myeloid leukemiaRelapsing acute myeloid leukemiaAcute Lymphoblastic Leukemia+ [4]

Inactive Indication-

Originator Organization

Meryx, Inc.

Active Organization

Meryx, Inc.

Betta Pharmaceuticals Co., Ltd.

Inactive Organization-

Drug Highest PhasePhase 1/2

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC29H40N6O

InChIKeyLBEJYFVJIPQSNX-SOAUALDESA-N

CAS Registry1429882-07-4

This is a Phase I, open-label, non-randomized, dose escalation study in adolescents and adults with relapsed/refractory acute myeloid leukemia, acute lymphoblastic leukemia, or mixed phenotype acute leukemia. Patients will receive continuous oral MRX-2843 in 28 day cycles at predefined dose cohorts.

Start Date01 Apr 2022

Sponsor / Collaborator

Meryx, Inc.

NCT04946890

/ Not yet recruitingPhase 1/2

Phase I/II Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Effectiveness of MRX2843 Tablets in Patients With Relapsed/Refractory Acute Myeloid Leukemia

Patients will receive oral MRX2843 for 28 days to study the side effects, tolerability and best dose for treating relapsed or refractory acute myeloid leukemia With FLT3 Mutations.

Start Date01 Jul 2021

Sponsor / Collaborator

Betta Pharmaceuticals Co., Ltd.

NCT04762199

/ RecruitingPhase 1IIT

A Phase 1b Safety and Pharmacodynamic Study of MER Tyrosine Kinase Inhibitor, MRX-2843, in Combination With Osimertinib in Advanced EGFR Mutant Non-Small Cell Lung Cancer

This phase Ib trial evaluates the best dose and side effects of MRX-2843 when given in combination with osimertinib in treating patients with EGFR gene mutant non-small cell lung cancer that has spread to other places in the body (advanced). MRX-2843 and osimertinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Start Date24 Feb 2021

Sponsor / Collaborator

Emory University

[+1]

100 Clinical Results associated with MRX-2843

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100 Translational Medicine associated with MRX-2843

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100 Patents (Medical) associated with MRX-2843

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37

Literatures (Medical) associated with MRX-2843

08 Jan 2025·Journal of Agricultural and Food Chemistry

A Disintegrin and Metalloproteinase 17 Disrupts Bovine Macrophage MER Proto-Oncogene Tyrosine Kinase Integrity to Impede Apoptotic Cell Clearance and Promote Inflammation in Clinical Mastitis

Article

Author: Usman, Muhammad ; Zhao, Bichen ; Li, Ming ; Chang, Renxu ; Loor, Juan J. ; Wu, Wenda ; Zhang, Huijing ; Wang, Jingyi ; Xu, Chuang

In clinical mastitis of dairy cows, the abnormal accumulation of apoptotic cells (ACs) and subsequent secondary necrosis and inflammation pose significant concerns, with macrophage-mediated efferocytosis, crucial for ACs clearance, remaining unexplored in this context. In nonruminants, MER proto-oncogene tyrosine kinase (MERTK) receptors are essential for efferocytosis and A Disintegrin and Metalloproteinase 17 (ADAM17) is thought to play a role in regulating MERTK integrity. This study aimed to delineate the in situ role of efferocytosis in clinical mastitis, with a particular focus on the interaction between MERTK and ADAM17 in bovine macrophages. In mastitic mammary tissue, a significant accumulation of ACs was observed, along with active macrophage efferocytosis. Western blotting analysis revealed elevated expressions of MERTK and ADAM17, and immunofluorescence confirmed that MERTK is predominantly localized within CD163⁺ macrophages. Additionally, elevated levels of soluble MERTK (sol-MER) in serum indicated impaired integrity and functionality of MERTK. In vitro experiments with the bovine macrophage cell line Bo-mac cells selectively phagocytosed apoptotic MAC-T cells, a process associated with increased MERTK phosphorylation and an anti-inflammatory phenotype. The activation of ADAM17 by Phorbol 12-myristate 13-acetate (PMA) induced sol-Mer release and impaired efferocytosis, with these effects reversed by the ADAM17 inhibitor TAPI-1. Bo-mac efferocytosis was influenced by the presence and activation of MERTK. Silencing MERTK interrupted efferocytosis, a phenomenon also observed with the inhibition of MERTK phosphorylation by UNC2025, which concurrently suppressed anti-inflammatory cytokine production. These findings suggest that targeting the MERTK-ADAM17 axis could enhance inflammatory resolution, providing a novel therapeutic strategy for dairy cattle health management.

01 Dec 2024·Leukemia

MERTK inhibition selectively activates a DC – T-cell axis to provide anti-leukemia immunity

Article

Author: Graham, Douglas K. ; DeRyckere, Deborah ; Baxter, Travon A ; Jacobsen, Kristen M. ; Chimenti, Madison L. ; Graham, Douglas K ; Frye, Stephen V ; Bakhtiari, Mojtaba ; Henry, Curtis J. ; Jacobsen, Kristen M ; Thomas, Beena E ; Bhasin, Swati S. ; Bhasin, Manoj ; Yim, Juhye ; Raikar, Sunil S ; Huelse, Justus M. ; Branella, Gianna M ; Earp, H. Shelton ; Bhasin, Swati S ; Frye, Stephen V. ; Branella, Gianna M. ; Huelse, Justus M ; Thomas, Beena E. ; Earp, H Shelton ; Chimenti, Madison L ; Baxter, Travon A. ; Raikar, Sunil S. ; Henry, Curtis J ; Wang, Xiaodong

TAM-family tyrosine kinases (TYRO3, AXL and MERTK) are potential cancer therapeutic targets. In previous studies MERTK inhibition in the immune microenvironment was therapeutically effective in a B-cell acute leukemia (B-ALL) model. Here, we probed anti-leukemia immune mechanisms and evaluated roles for TYRO3 and AXL in the leukemia microenvironment. Host Mertk knock-out or MERTK inhibitor MRX-2843 increased CD8α⁺ dendritic cells (DCs) with enhanced antigen-presentation capacity in the leukemia microenvironment and inhibited leukemogenesis. High MERTK or low DC gene expression were associated with poor prognosis in pediatric ALL patients, indicating the clinical relevance of these findings. MRX-2843 increased CD8⁺ T-cell numbers and prevented induction of exhaustion markers, implicating a DC - T-cell axis. Indeed, combined depletion of CD8α⁺ DCs and CD8⁺ T-cells was required to abrogate anti-leukemia immunity in Mertk^-/- mice. Tyro3^-/- mice were also protected against B-ALL, implicating TYRO3 as an immunotherapeutic target. In contrast to Mertk^-/- mice, Tyro3^-/- did not increase CD8α⁺ DCs with enhanced antigen-presentation capacity and therapeutic activity was less dependent on DCs, indicating a different immune mechanism. Axl^-/- did not impact leukemogenesis. These data demonstrate differential TAM kinase roles in the leukemia microenvironment and provide rationale for development of MERTK and/or TYRO3-targeted immunotherapies.

07 Oct 2024·Oncogene

Targeting MERTK on tumour cells and macrophages: a potential intervention for sporadic and NF2-related meningioma and schwannoma tumours

Article

Author: Ercolano, Emanuela ; Hanemann, C. Oliver ; Adams, Claire L ; Dave, Foram ; Hilton, David A. ; Kurian, Kathreena M ; van de Weijer, Laurien L ; Henderson, Summer ; van de Weijer, Laurien L. ; Herrera, Kevin ; Sofela, Agbolahan A. ; Maze, Emmanuel A ; Sofela, Agbolahan A ; Lockley, Alex ; Kurian, Kathreena M. ; Adams, Claire L. ; Ammoun, Sylwia ; Maze, Emmanuel A. ; Hilton, David A ; Hook, Laura ; Hanemann, C Oliver

Meningioma and schwannoma are common tumours of the nervous system. They occur sporadically or as part of the hereditary NF2-related schwannomatosis syndrome. There is an unmet need for new effective drug treatments for both tumour types. In this paper, we demonstrate overexpression/activation of TAM (TYRO3/AXL/MERTK) receptors (TAMs) and overexpression/release of ligand GAS6 in patient-derived meningioma tumour cells and tissue. For the first time, we reveal the formation of MERTK/TYRO3 heterocomplexes in meningioma and schwannoma tissue. We demonstrate the dependence of AXL and TYRO3 expression on MERTK in both tumour types, as well as interdependency of MERTK and AXL expression in meningioma. We show that MERTK and AXL contribute to increased proliferation and survival of meningioma and schwannoma cells, which we inhibited in vitro using the MERTK/FLT3 inhibitor UNC2025 and the AXL inhibitor BGB324. UNC2025 was effective in both tumour types with superior efficacy over BGB324. Finally, we found that TAMs are expressed by tumour-associated macrophages in meningioma and schwannoma tumours and that UNC2025 strongly depleted macrophages in both tumour types.

100 Deals associated with MRX-2843

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Refractory acute myeloid leukemia	Phase 2	CN	Betta Pharmaceuticals Co., Ltd.	01 Jul 2021
Relapsing acute myeloid leukemia	Phase 2	CN	Betta Pharmaceuticals Co., Ltd.	01 Jul 2021
Acute Lymphoblastic Leukemia	Phase 1	US	Meryx, Inc.	01 Apr 2022
Mixed phenotype acute leukemia	Phase 1	US	Meryx, Inc.	01 Apr 2022
Advanced Malignant Solid Neoplasm	Phase 1	CN	Betta Pharmaceuticals Co., Ltd.	07 Jul 2020
Advanced cancer	Phase 1	US	Meryx, Inc.	22 May 2018
Solid tumor	Phase 1	US	Meryx, Inc.	22 May 2018

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04762199 (WCLC2024) Manual	Phase 1	EGFR-mutated non-small Cell Lung Cancer	21	MRX-2843osimertinib	(qwodybfuuq) = aqbuveftcp bysgadvsve (vmeumqwmlv ) View more	Positive	08 Sep 2024