- |||||||||| Review, Journal: Recent progress on tyrosine kinase 2 JH2 inhibitors. (Pubmed Central) - Oct 22, 2023
Interest in TYK2 JH2 inhibitors has increased as a result of safety concerns with JAK inhibitors. This overview introduces TYK2 JH2 inhibitors that are already on the market, including Deucravactinib (BMS-986165), as well as those currently in clinical trials, such as BMS-986202, NDI-034858, and ESK-001.
- |||||||||| BMS-986020 / BMS
Preclinical, Journal: Predicting the preclinical efficacy of anti-fibrosis agents using a force-sensing fibrosis on chip system. (Pubmed Central) - Mar 28, 2023 Both pre-approval drugs were effective in inhibiting transforming growth factor beta 1 (TGF-?1) induced increases in tissue contractile force, stiffness and expressions of fibrotic biomarkers, which are similar to the effects of FDA-approved anti-fibrosis drugs. These results demonstrated the potential utility of the force-sensing fibrosis on chip system in the pre-clinical development of anti-fibrosis drugs.
- |||||||||| LTSE / Structure Therap, BMS-986020 / BMS
Structure Based Discovery and Anti-fibrotic Activity of Novel Antagonists of Lysophosphatidic Acid Receptor 1 (LPAR1) (Walter E. Washington Convention Center, Area J, Hall C (Lower Level)) - Mar 25, 2023 - Abstract #ATS2023ATS_5625; The 1st generation LPAR1 antagonist, BMS-986020, demonstrated a significant reduction in forced vital capacity (FVC) decline in a 6-month phase II trial in IPF patients but was terminated due to compound-specific hepatobiliary toxicity...Lead compounds were evaluated for LPAR1 antagonist activity in a mouse model of LPA-mediated histamine release, anti-fibrotic efficacy in a mouse model of bleomycin induced lung fibrosis, and toxicity in preclinical species. Structure-based drug design and Schr
- |||||||||| Xeljanz (tofacitinib) / Pfizer, BMS-986020 / BMS
Tyrosine Kinase 2 Inhibition Ameliorates the Phenotype of Lesional Alopecia Areata Scalp Skin Ex Vivo, and Reverses the Induction of Human Alopecia Areata in a Humanized Mouse Model (Kiosk #1) - Aug 16, 2022 - Abstract #ESDR2022ESDR_699; In the humanized mouse model, treatment with BMS or tofacitinib significantly increased hair shaft numbers and microscopically detected anagen I-VI HFs, reduced HM keratinocyte apoptosis and HF dystrophy, decreased MHC class I and II expression, and diminished numbers of MHC class II+ cells and infiltrating CD3+ T cells. Taken together, our results suggest TYK2 inhibition is a novel, pharmacological strategy for AA management, deserving clinical exploration.
- |||||||||| HZN-825 / Horizon Therapeutics, BMS-986278 / BMS, BMS-986020 / BMS
Review, Journal: The development of modulators for lysophosphatidic acid receptors: A comprehensive review. (Pubmed Central) - Jan 15, 2022 While no drugs targeting LPARs have been approved by the FDA thus far, at least three antagonists have entered phase Ⅱ clinical trials for idiopathic pulmonary fibrosis (BMS-986020 and BMS-986278) and systemic sclerosis (SAR100842), and one radioligand (BMT-136088/F-BMS-986327) has entered phase Ⅰ clinical trials for positron emission tomography (PET) imaging of idiopathic pulmonary fibrosis. This article provides an extensive review on the current status of ligand development targeting LPA receptors to modulate LPA signaling and their therapeutic potential in various diseases.
- |||||||||| BMS-986020 / BMS
Clinical, Clinical data, P2 data, Journal: The value of imaging and clinical outcomes in a phase II clinical trial of a lysophosphatidic acid receptor antagonist in idiopathic pulmonary fibrosis. (Pubmed Central) - Nov 17, 2021 This study assessed quantitative scores from high-resolution computed tomography (HRCT) developed by machine learning as a secondary efficacy endpoint in a 26-week phase II study of BMS-986020 - an LPA receptor antagonist - in patients with IPF...Significant correlations were found between changes in QLF and changes in percent predicted FVC, diffusing capacity for carbon monoxide (DLCO), and shortness of breath at week 26 (ρ = -0.41, ρ = -0.22, and ρ = 0.27, respectively; all p < 0.01). This study demonstrated the utility of quantitative HRCT as an efficacy endpoint for IPF in a double-blind, placebo-controlled clinical trial setting.The reviews of this paper are available via the supplemental material section.
- |||||||||| anti-MICA/B antibody / BMS, BMS-986020 / BMS
[VIRTUAL] Selective inhibition of tyrosine kinase 2 prevents and restores interleukin-12- induced hair follicle immune privilege collapse: a novel approach to alopecia areata therapy? () - Aug 23, 2021 - Abstract #ESDR2021ESDR_226; By quantitative immunohistomorphometry, we showed that ex vivo treatment of microdissected HFs with IL-12 (3 ng/mL) + IL-18 (20 ng/mL) upregulated MHC-I and II as well as MICA/B expression in the hair bulb (cardinal features of IP collapse), increased the numbers of CD3+ or CD56+ cells in HF epithelium and mesenchyme, and selectively enriched IFNginducible genes...Therefore, our data demonstrate that local IL-12 directly promotes perifollicular immune cell expansion, IFNg secretion, and HF-IP collapse. These findings support a potential role of IL12 signaling in AA pathogenesis and highlight IL-12 as a potential new target for pharmacologic AA therapy
- |||||||||| BMS-986020 / BMS
Clinical, Journal: Discovery of BMS-986202: A Clinical Tyk2 Inhibitor that Binds to Tyk2 JH2. (Pubmed Central) - Mar 9, 2021 When the diversity search was extended to nicotinamides, a single fluorine atom addition was found to significantly enhance the permeability, which directly led to the discovery of 7 (BMS-986202) as a clinical Tyk2 inhibitor that binds to Tyk2 JH2. The preclinical studies of 7, including efficacy studies in mouse models of IL-23-driven acanthosis, anti-CD40-induced colitis, and spontaneous lupus, will also be presented.
- |||||||||| BMS-986020 / BMS
Evaluation of Collagen Neoepitope Biomarkers in a Phase 2 Trial of BMS-986020, A Lysophosphatidic Acid Receptor Antagonist, for the Treatment of Idiopathic Pulmonary Fibrosis (PENNSYLVANIA CONVENTION CENTER, Terrace Ballroom II (Terrace Ballroom Level)) - Mar 15, 2020 - Abstract #ATS2020ATS_2934; Conclusions : The data suggest that LPA 1 pathway antagonism can impact collagen turnover and matrix remodeling in IPF lung and that C3M, PRO-C4 and C6M may have potential value as biomarkers to monitor treatment response and disease progression/regression in future clinical trials. The data suggest that LPA1 pathway antagonism can impact collagen turnover and matrix remodeling in IPF lung and that C3M, PRO-C4 and C6M may have potential value as biomarkers to monitor treatment response and disease progression/regression in future clinical trials.
- |||||||||| BMS-986278 / BMS
LPA1 antagonist BMS-986278 for idiopathic pulmonary fibrosis: Preclinical pharmacological in vitro and in vivo evaluation (6A) - Aug 26, 2019 - Abstract #ERS2019ERS_5748; The LPA 1 antagonist BMS-986020 600 mg BID was efficacious in a 6-month placebo-controlled Phase 2 clinical trial in IPF patients by slowing lung function decline as measured by rate of decline of forced vital capacity (FVC) (CHEST, 154, p1061–69, 2018)...In vivo, BMS-986278: 1) inhibits LPA-stimulated histamine release in mice; 2) demonstrates antifibrotic activity, as shown by decreases in picrosirius red staining area of the lung in the chronic rodent bleomycin model...BMS-986278 has negligible activity at bile acid and other clinically relevant drug transporters (BSEP, MDR3 IC 50 = >100 μM; OATP1B1 IC 50 = 35.5 μM). BMS-986278 represents a novel promising LPA1 antagonist for the treatment of multiple fibrotic diseases.
- |||||||||| BMS-986020 / BMS
Trial completion: Drug Interaction Study With Rosuvastatin (clinicaltrials.gov) - Jun 13, 2014 P1, N=26, Completed, Not yet recruiting --> Active, not recruiting Not yet recruiting --> Completed
|