Delving into the Latest Updates on Edicotinib with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Edicotinib (USAN), Edicotinib hydrochloride

+ [5]

Target

CSF-1R

Mechanism

CSF-1R antagonists(Colony stimulating factor 1 receptor antagonists)

Therapeutic Areas

NeoplasmsImmune System DiseasesDigestive System Disorders+ [4]

Active Indication-

Inactive Indication

Alzheimer DiseaseCrohn DiseaseMild cognitive disorder+ [3]

Originator Organization

Johnson & Johnson

Active Organization-

Inactive Organization

Janssen Research & Development LLC

Janssen Pharmaceutica NV

Provention Bio, Inc.

+ [2]

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC27H35N5O2

InChIKeyBNVPFDRNGHMRJS-UHFFFAOYSA-N

CAS Registry1142363-52-7

A phase 1 randomised, placebo-controlled, single-blind study to characterise the biomarker effects of the CSF-1 receptor antagonist JNJ-40346527 in participants with mild cognitive impairment. A maximum of 54 participants will be recruited to the two part study. The first part of the study will identify whether it is possible to identify biomarkers that may be used in future studies with JNJ-40346527 and part 2 will investigate a minimal efficacious JNJ-40346527 dose.

Start Date07 Apr 2021

Sponsor / Collaborator

University of Oxford

[+1]

NCT03557970 / TerminatedPhase 2IIT

A Phase 2 Open-Label Study of the CSF-1R Inhibitor JNJ-40346527 in Patients With Relapsed/Refractory Acute Myeloid Leukemia (AML)

This phase II trial studies how well edicotinib (JNJ-40346527) works in treating participants with acute myeloid leukemia that has come back or does not respond to treatment. JNJ-40346527 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Start Date05 Oct 2018

Sponsor / Collaborator

OHSU Knight Cancer Institute

[+3]

NCT03854305 / CompletedPhase 2

Phase 2a Multicenter Randomized Double-Blind Placebo-Controlled Parallel Study to Evaluate the Efficacy and Safety of Oral PRV-6527 (JNJ-40346527), an Inhibitor of CSF-1 Receptor, in Subjects With Moderately to Severely Active Crohn's

This study will evaluate the efficacy and safety of oral PRV-6527 in the treatment of moderately to severely active Crohn's disease

Start Date20 Mar 2018

Sponsor / Collaborator

Provention Bio, Inc.

100 Clinical Results associated with Edicotinib

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100 Translational Medicine associated with Edicotinib

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100 Patents (Medical) associated with Edicotinib

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10

Literatures (Medical) associated with Edicotinib

01 Nov 2024·Biomedicine & Pharmacotherapy

The colony-stimulating factor-1 receptor inhibitor edicotinib counteracts multidrug resistance in cancer cells by inhibiting ABCG2-mediated drug efflux

Article

Author: Huang, Yang-Hui ; Wu, Chung-Pu ; Lee, Yun-Chieh ; Ambudkar, Suresh V ; Murakami, Megumi ; Ambudkar, Suresh.V. ; Li, Yen-Ching ; Hung, Tai-Ho ; Wu, Yu-Shan

Chemotherapy treatment faces a major obstacle with the emergence of multidrug resistance (MDR), often attributed to the elevated expression of ATP-binding cassette (ABC) transporters such as ABCG2 and ABCB1 in cancer cells. These transporters hinder the efficacy of cytotoxic drugs via ATP hydrolysis-dependent efflux, leading to diminished intracellular drug levels. The scarcity of approved treatments for multidrug resistant cancers necessitates exploration of alternative strategies, including drug repositioning of molecular targeted agents to counteract ABCG2-mediated MDR in multidrug-resistant cancer cells. This study investigates the potential of edicotinib, a selective colony-stimulating factor-1 receptor (CSF-1R) tyrosine kinase inhibitor that is currently undergoing clinical trials for various diseases, to reverse MDR in ABCG2-overexpressing cancer cells. Our findings reveal that by attenuating the drug-efflux function of ABCG2 without altering its expression, edicotinib improves drug-induced apoptosis and reverses MDR in ABCG2-overexpressing multidrug-resistant cancer cells at non-toxic concentrations. Through ATPase activity analysis and molecular docking, potential interaction sites for edicotinib on ABCG2 were identified. These results underscore an additional pharmacological benefit of edicotinib against ABCG2 activity, suggesting its potential incorporation into combination therapies for patients with ABCG2-overexpressing tumors. Further research is warranted to validate these findings and explore their clinical implications.

09 Apr 2023·Journal of neuroinflammation

Pharmacological modulation of TSPO in microglia/macrophages and neurons in a chronic neurodegenerative model of prion disease.

Article

Author: Peris-Yague, Alba ; Simmons, Camilla ; Vicente-Rodríguez, Marta ; Gómez-Nicola, Diego ; Cash, Diana ; Turkheimer, Federico ; Mancuso, Renzo ; Perry, V Hugh ; Parker, Christine A ; Lovestone, Simon

Neuroinflammation is an important component of many neurodegenerative diseases, whether as a primary cause or a secondary outcome. For that reason, either as diagnostic tools or to monitor progression and/or pharmacological interventions, there is a need for robust biomarkers of neuroinflammation in the brain. Mitochondrial TSPO (18 kDa Translocator protein) is one of few available biomarkers of neuroinflammation for which there are clinically available PET imaging agents. In this study, we further characterised neuroinflammation in a mouse model of prion-induced chronic neurodegeneration (ME7) including a pharmacological intervention via a CSF1R inhibitor. This was achieved by autoradiographic binding of the second-generation TSPO tracer, [3H]PBR28, along with a more comprehensive examination of the cellular contributors to the TSPO signal changes by immunohistochemistry. We observed regional increases of TSPO in the ME7 mouse brains, particularly in the hippocampus, cortex and thalamus. This increased TSPO signal was detected in the cells of microglia/macrophage lineage as well as in astrocytes, endothelial cells and neurons. Importantly, we show that the selective CSF1R inhibitor, JNJ-40346527 (JNJ527), attenuated the disease-dependent increase in TSPO signal, particularly in the dentate gyrus of the hippocampus, where JNJ527 attenuated the number of Iba1+ microglia and neurons, but not GFAP+ astrocytes or endothelial cells. These findings suggest that [3H]PBR28 quantitative autoradiography in combination with immunohistochemistry are important translational tools for detecting and quantifying neuroinflammation, and its treatments, in neurodegenerative disease. Furthermore, we demonstrate that although TSPO overexpression in the ME7 brains was driven by various cell types, the therapeutic effect of the CSF1R inhibitor was primarily to modulate TSPO expression in microglia and neurons, which identifies an important route of biological action of this particular CSF1R inhibitor and provides an example of a cell-specific effect of this type of therapeutic agent on the neuroinflammatory process.

01 Mar 2023·Journal for ImmunoTherapy of Cancer

Immune and pathologic responses in patients with localized prostate cancer who received daratumumab (anti-CD38) or edicotinib (CSF-1R inhibitor)

Article

Author: Logothetis, Christopher J ; Gu, Ai-Di ; Tidwell, Rebecca S S ; Chapin, Brian F ; Kinder, Michelle ; Drake, Charles G ; Basu, Sreyashi ; Subudhi, Sumit K ; Yadav, Shalini S ; Hutnick, Natalie ; Siddiqui, Bilal A ; Sharma, Padmanee ; Duan, Fei ; Pettaway, Curtis A ; Troncoso, Patricia ; Corn, Paul G ; Ward, John F ; Gottardis, Marco ; Jindal, Sonali ; Knoblauch, Roland ; Espejo, Alexsandra B

BackgroundThe prostate tumor microenvironment (TME) is immunosuppressive, with few effector T cells and enrichment of inhibitory immune populations, leading to limited responses to treatments such as immune checkpoint therapies (ICTs). The immune composition of the prostate TME differs across soft tissue and bone, the most common site of treatment-refractory metastasis. Understanding immunosuppressive mechanisms specific to prostate TMEs will enable rational immunotherapy strategies to generate effective antitumor immune responses. Daratumumab (anti-CD38 antibody) and edicotinib (colony-stimulating factor-1 receptor (CSF-1R) inhibitor) may alter the balance within the prostate TME to promote antitumor immune responses.HypothesisDaratumumab or edicotinib will be safe and will alter the immune TME, leading to antitumor responses in localized prostate cancer.Patients and methodsIn this presurgical study, patients with localized prostate cancer received 4 weekly doses of daratumumab or 4 weeks of daily edicotinib prior to radical prostatectomy (RP). Treated and untreated control (Gleason score ≥8 in prostate biopsy) prostatectomy specimens and patient-matched pre- and post-treatment peripheral blood mononuclear cells (PBMCs) and bone marrow samples were evaluated. The primary endpoint was incidence of adverse events (AEs). The secondary endpoint was pathologic complete remission (pCR) rate.ResultsTwenty-five patients were treated (daratumumab, n=15; edicotinib, n=10). All patients underwent RP without delays. Grade 3 treatment-related AEs with daratumumab occurred in 3 patients (12%), and no ≥grade 3 treatment-related AEs occurred with edicotinib. No changes in serum prostate-specific antigen (PSA) levels or pCRs were observed. Daratumumab led to a decreased frequency of CD38+T cells, natural killer cells, and myeloid cells in prostate tumors, bone marrow, and PBMCs. There were no consistent changes in CSF-1R+immune cells in prostate, bone marrow, or PBMCs with edicotinib. Neither treatment induced T cell infiltration into the prostate TME.ConclusionsDaratumumab and edicotinib treatment was safe and well-tolerated in patients with localized prostate cancer but did not induce pCRs. Decreases in CD38+immune cells were observed in prostate tumors, bone marrow, and PBMCs with daratumumab, but changes in CSF-1R+immune cells were not consistently observed with edicotinib. Neither myeloid-targeted agent alone was sufficient to generate antitumor responses in prostate cancer; thus, combinations with agents to induce T cell infiltration (eg, ICTs) will be needed to overcome the immunosuppressive prostate TME.

100 Deals associated with Edicotinib

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External Link

KEGG	Wiki	ATC	Drug Bank
D11378	-	-	DB12504

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Rheumatoid Arthritis	Phase 2	KR	Janssen Research & Development LLC	01 Jul 2012
Rheumatoid Arthritis	Phase 2	CZ	Janssen Research & Development LLC	01 Jul 2012
Rheumatoid Arthritis	Phase 2	UA	Janssen Research & Development LLC	01 Jul 2012
Rheumatoid Arthritis	Phase 2	PL	Janssen Research & Development LLC	01 Jul 2012
Rheumatoid Arthritis	Phase 2	HU	Janssen Research & Development LLC	01 Jul 2012
Rheumatoid Arthritis	Phase 2	AR	Janssen Research & Development LLC	01 Jul 2012
Rheumatoid Arthritis	Phase 2	CL	Janssen Research & Development LLC	01 Jul 2012
Rheumatoid Arthritis	Phase 2	RU	Janssen Research & Development LLC	01 Jul 2012
Rheumatoid Arthritis	Phase 2	BG	Janssen Research & Development LLC	01 Jul 2012
Rheumatoid Arthritis	Phase 2	SG	Janssen Research & Development LLC	01 Jul 2012

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01597739 (Pubmed \| J Rheumatol) Manual	Phase 2	Rheumatoid Arthritis	95	JNJ-40346527	(olibxyvgdr) = kcsvgbxniw xbouzzubhf (givncagglg ) View more	Negative	01 Oct 2015
				Placebo	(olibxyvgdr) = adxxylsyod xbouzzubhf (givncagglg ) View more