scholarly journals Discovery of a First-in-Class Gut-Restricted RET Kinase Inhibitor as a Clinical Candidate for the Treatment of IBS

2018 ◽  
Vol 9 (7) ◽  
pp. 623-628 ◽  
Author(s):  
Hilary Schenck Eidam ◽  
John Russell ◽  
Kaushik Raha ◽  
Michael DeMartino ◽  
Donghui Qin ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Clinical Candidate

scholarly journals Saracatinib is an efficacious clinical candidate for fibrodysplasia ossificans progressiva

2020 ◽  
Author(s):  
Eleanor Williams ◽  
Jana Bagarova ◽  
Georgina Kerr ◽  
Dong-Dong Xia ◽  
Elsie S. Place ◽  
...  
Keyword(s):  
Heterotopic Ossification ◽  
Soft Tissues ◽  
Kinase Inhibitor ◽  
Tissue Injury ◽  
Soft Tissue Injury ◽  
Biologically Active ◽  
Fibrodysplasia Ossificans Progressiva ◽  
Heterotopic Bone ◽  
Transgenic Mouse Line ◽  
Clinical Candidate

AbstractCurrently, no effective therapies exist for fibrodysplasia ossificans progressiva (FOP), a rare congenital syndrome in which heterotopic bone is formed in soft tissues due to dysregulated activity of the bone morphogenetic protein (BMP) receptor kinase ALK2/ACVR1. From a screen of known biologically active compounds, we identified saracatinib as a potent ALK2 kinase inhibitor. In enzymatic and cell-based assays, saracatinib preferentially inhibited ALK2 compared with other receptors of the BMP/TGFβ signaling pathway, and induced dorsalization in zebrafish embryos consistent with BMP antagonism. We further tested the efficacy of saracatinib using an inducible ACVR1Q207D transgenic mouse line, which provides a model of heterotopic ossification, as well as an inducible ACVR1R206H knock-in, which serves as a genetically and physiologically faithful model of FOP. In both models, saracatinib was well tolerated and potently inhibited the development of heterotopic ossification even when administered transiently following soft tissue injury. Together, these data suggest that saracatinib is an efficacious clinical candidate for repositioning in the treatment of FOP, offering an accelerated path to clinical proof of efficacy studies and potentially significant benefits to individuals with this devastating condition.

scholarly journals Identification of a RIP1 Kinase Inhibitor Clinical Candidate (GSK3145095) for the Treatment of Pancreatic Cancer

2019 ◽  
Vol 10 (6) ◽  
pp. 857-862 ◽  
Author(s):  
Philip A. Harris ◽  
Jill M. Marinis ◽  
John D. Lich ◽  
Scott B. Berger ◽  
Anirudh Chirala ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Kinase Inhibitor ◽  
Clinical Candidate

Discovery of ATR kinase inhibitor berzosertib (VX-970, M6620): Clinical candidate for cancer therapy

2020 ◽  
Vol 210 ◽  
pp. 107518 ◽  
Author(s):  
Lukas Gorecki ◽  
Martin Andrs ◽  
Martina Rezacova ◽  
Jan Korabecny
Keyword(s):  
Cancer Therapy ◽  
Kinase Inhibitor ◽  
Atr Kinase ◽  
Clinical Candidate
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