Tao Wang1, Dingwei Yu, Michelle L Lamb. 1. Cancer Discovery, AstraZeneca R&D Boston, Waltham, MA 02451, USA. tao.wang@astrazeneca.com
Abstract
BACKGROUND: Tropomyosin-related kinases (Trks) are a family of receptor tyrosine kinases activated by neurotrophins. Trks play important roles in pain sensation as well as tumour cell growth and survival signaling. Thus, inhibitors of Trk receptor kinases might provide targeted treatments for pain and cancer. OBJECTIVE: This paper reviews those patent applications since 2002 claiming small-molecule inhibitors of Trk receptor kinases. METHODS: Primary literature and patents were searched with SciFinder and Google Scholar. Patents were selected based on their relevance to Trks and were evaluated and representative compounds were listed as examples. RESULTS/ CONCLUSION: Several series of Trk inhibitors with excellent in vitro potencies have been reported and a number of compounds have gone into the clinic. It should be noted that few of these inhibitors are Trk selective, demonstrating that targeting Trk kinases for treatment of pain and/or cancer offers a promising but also challenging approach.
BACKGROUND: Tropomyosin-related kinases (Trks) are a family of receptor tyrosine kinases activated by neurotrophins. Trks play important roles in pain sensation as well as tumour cell growth and survival signaling. Thus, inhibitors of Trk receptor kinases might provide targeted treatments for pain and cancer. OBJECTIVE: This paper reviews those patent applications since 2002 claiming small-molecule inhibitors of Trk receptor kinases. METHODS: Primary literature and patents were searched with SciFinder and Google Scholar. Patents were selected based on their relevance to Trks and were evaluated and representative compounds were listed as examples. RESULTS/ CONCLUSION: Several series of Trk inhibitors with excellent in vitro potencies have been reported and a number of compounds have gone into the clinic. It should be noted that few of these inhibitors are Trk selective, demonstrating that targeting Trk kinases for treatment of pain and/or cancer offers a promising but also challenging approach.
Authors: Zongli Zheng; Matthew Liebers; Boryana Zhelyazkova; Yi Cao; Divya Panditi; Kerry D Lynch; Juxiang Chen; Hayley E Robinson; Hyo Sup Shim; Juliann Chmielecki; William Pao; Jeffrey A Engelman; A John Iafrate; Long Phi Le Journal: Nat Med Date: 2014-11-10 Impact factor: 53.440
Authors: Pam Albaugh; Yi Fan; Yuan Mi; Fangxian Sun; Francisco Adrian; Nanxin Li; Yong Jia; Yelena Sarkisova; Andreas Kreusch; Tami Hood; Min Lu; Guoxun Liu; Shenlin Huang; Zuosheng Liu; Jon Loren; Tove Tuntland; Donald S Karanewsky; H Martin Seidel; Valentina Molteni Journal: ACS Med Chem Lett Date: 2012-01-01 Impact factor: 4.345
Authors: Tao Wang; Michelle L Lamb; Michael H Block; Audrey Molina Davies; Yongxin Han; Ethan Hoffmann; Stephanos Ioannidis; John A Josey; Zhong-Ying Liu; Paul D Lyne; Terry MacIntyre; Peter J Mohr; Charles A Omer; Tove Sjögren; Kenneth Thress; Bin Wang; Haiyun Wang; Dingwei Yu; Hai-Jun Zhang Journal: ACS Med Chem Lett Date: 2012-07-26 Impact factor: 4.345
Authors: Hua-Poo Su; Keith Rickert; Christine Burlein; Kartik Narayan; Marina Bukhtiyarova; Danielle M Hurzy; Craig A Stump; Xufang Zhang; John Reid; Alicja Krasowska-Zoladek; Srivanya Tummala; Jennifer M Shipman; Maria Kornienko; Peter A Lemaire; Daniel Krosky; Amanda Heller; Abdelghani Achab; Chad Chamberlin; Peter Saradjian; Berengere Sauvagnat; Xianshu Yang; Michael R Ziebell; Elliott Nickbarg; John M Sanders; Mark T Bilodeau; Steven S Carroll; Kevin J Lumb; Stephen M Soisson; Darrell A Henze; Andrew J Cooke Journal: Proc Natl Acad Sci U S A Date: 2016-12-30 Impact factor: 11.205
Authors: Lisa A Cannon-Albright; Craig C Teerlink; James M Farnham; Alun W Thomas; John J Zone; Sancy A Leachman Journal: J Invest Dermatol Date: 2012-09-06 Impact factor: 8.551