IL-2R antagonists(Interleukin-2 receptor antagonists), TNF-α inhibitors(Tumor necrosis factor α inhibitors), p38α inhibitors(P38 α mitogen-activated protein kinase inhibitors)

Therapeutic Areas

Immune System DiseasesInfectious DiseasesDigestive System Disorders+ [2]

Active Indication-

Inactive Indication

ArthritisHIV InfectionsInflammatory Bowel Diseases+ [1]

Originator Organization

Janssen Global Services LLC

Active Organization-

Inactive Organization

Johnson & Johnson Pharmaceutical Research & Development LLC

Janssen Global Services LLC

Drug Highest PhaseDiscontinuedPhase 1

First Approval Date-

Regulation-

Structure

Molecular FormulaC27H24FN3O

InChIKeyQSUSKMBNZQHHPA-UHFFFAOYSA-N

CAS Registry215303-72-3

100 Clinical Results associated with RWJ-67657

100 Translational Medicine associated with RWJ-67657

100 Patents (Medical) associated with RWJ-67657

Literatures (Medical) associated with RWJ-67657

01 Nov 2023·Parasitology

Anti-Toxoplasma gondii screening of MMV pandemic response box and evaluation of RWJ-67657 efficacy in chronically infected mice

Article

Author: Reimão, Juliana Quero ; Marques, Marcos José ; Ramos, Amanda Bruno da Silva Bellini ; Dos Santos, Bruna Ramos ; de Menezes, Renata Priscila Barros ; Scotti, Marcus Tullius ; Colombo, Fábio Antônio

AbstractToxoplasmosis is a significant public health concern with limited therapeutic options. The medicines for malaria venture (MMV) developed the pandemic response box (PRB) containing 400 drug-like molecules with broad pathogen activity. The aim of this work is to evaluate PRB compounds for their anti-Toxoplasma gondii activity and identify promising candidates for further evaluation. Screening identified 42 selective compounds with half effective concentration (EC50) ranging from 2.4 to 913.1 nm and half cytotoxic concentration (CC50) ranging from 6 μm to >50 μm. Selectivity index (SI) values (CC50/EC50) ranged from 11 to 17 708. Based on its in silico and in vitro profile and its commercial availability, RWJ-67657 was selected for further studies. Molecular docking analysis showed RWJ-67657 is predicted to bind to T. gondii p38 mitogen-activated protein kinase (TgMAPK). Oral administration of RWJ-67657 (20 mg kg day−1/10 days) significantly reduced parasite burden in chronically infected mice compared to mock-treated group (P < 0.01). These findings highlight the PRB as a promising source for anti-T. gondii compounds, with several showing favourable drug properties, including MMV1634492, MMV002731, MMV1634491, MMV1581551, MMV011565, MMV1581558, MMV1578577, MMV233495 and MMV1580482, firstly described here as anti-T. gondii agents. RWJ-67657 emerges as a valuable drug candidate for experimental chronic cerebral toxoplasmosis therapy.

03 May 2022·Journal of Biomolecular Structure and Dynamics

p38α MAP kinase inhibitors to overcome EGFR tertiary C797S point mutation associated with osimertinib in non-small cell lung cancer (NSCLC): emergence of fourth-generation EGFR inhibitor

Article

Author: Ahmad, Iqrar ; Shaikh, Matin ; Surana, Sanjay ; Patel, Harun ; Ghosh, Arabinda

The third-generation EGFR (epidermal growth factor receptor) inhibitors selectively and irreversibly target EGFR-T790M and other activating EGFR mutations. Osimertinib is the only FDA-approved third-generation inhibitor, which has a good potency against the EGFR-T790M mutant with minimal toxicities and excellent selectivity for wild-type EGFR. EGFR tertiary Cys797 to Ser797 (C797S) point mutation emanate rapidly after the treatment of osimertinib, which is an undruggable mutation to all three existing generation drugs. Recently, trisubstituted imidazoles were reported based on an off-target hit of a p38α MAPK (mitogen-activated protein kinase) inhibitor as the fourth-generation EGFR-TKIs to overcome the C797S resistance by inhibiting the clinically relevant triple mutant kinase L858R/T790M/C797 EGFR. Here, we are reporting the clinical trial p38α MAPK kinase inhibitors SD-06, Amgen 16, RWJ67657 and SCIO-323 as L858R/T790M/C797S EGFR TK inhibitors to overcome the problem of drug resistance in non-small cell lung cancer (NSCLC).Communicated by Ramaswamy H. Sarma.

01 Oct 2021·IJC Heart & Vasculature

Insulin-like growth factor-1 directly affects cardiac cellular remodelling via distinct pathways

Article

Author: Bach, Leon A ; Wang, Ian H ; Fu, Ping ; Wang, Bing H ; Krum, Henry ; Huang, Kevin W

BACKGROUNDStudies of insulin-like growth factor 1 (IGF-1) as a novel therapy for the treatment of cardiovascular diseases have proven promising. However, elevated IGF-1 levels have also been associated with poor patient outcomes in heart failure with reduced ejection fraction. IGF-1 therapy has additionally been shown to not be beneficial in the percutaneous coronary intervention setting. Although IGF-1 activation of the PI3K/Akt and ERK1/2 pathways have been demonstrated as cardioprotective, other cellular mechanisms have not been fully investigated.METHODSNeonatal rat cardiac myocytes (NCMs) and fibroblasts (NCFs) were isolated from 1 to 2-day old pups using enzymatic digestion. NCMs and NCFs were pre-treated with IGF binding protein 6, inhibitors for the PI3K/Akt Wortmannin, ERK1/2 U0126, Rho Associated Protein Kinase (ROCK) GSK576371, Apoptosis Signal-regulating Kinase-1 (ASK-1) G2261818A, and p38MAPK RWJ67657 pathways before stimulation with IGF-1 for 62 and 50 h, respectively. Cardiac myocyte hypertrophy and fibroblast collagen synthesis were determined by ³H-leucine and ³H-proline incorporation, respectively.RESULTSIGF-1 dose-dependently stimulated NCM hypertrophy and NCF collagen synthesis.Treatment with IGFBP6 and the kinase inhibitors, Wortmannin, U0126, GSK576371, G2261818A and RWJ67657 significantly inhibited IGF-1 stimulated NCM hypertrophy and NCF collagen synthesis.CONCLUSIONThis study is the first to demonstrate that IGF-1 treatment in NCMs and NCFs activates the ROCK, ASK-1 and p38MAPK pathways. Future research may be guided by consideration of the PI3K/Akt and ERK1/2 pathways potentially increasing collagen synthesis, and the utilisation of a biased agonist to reduce activation of the ROCK, ASK-1 and p38MAPK pathways to maximise cardioprotective benefit whilst mitigating risks.

100 Deals associated with RWJ-67657

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Arthritis	Phase 1	-	Janssen Global Services LLC	-
HIV Infections	Phase 1	US	Johnson & Johnson Pharmaceutical Research & Development LLC	-
Inflammatory Bowel Diseases	Phase 1	-	Janssen Global Services LLC	-
Rheumatoid Arthritis	Phase 1	-	Johnson & Johnson Pharmaceutical Research & Development LLC	-

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