Literature DB >> 26288683

Discovery of a Highly Selective JAK2 Inhibitor, BMS-911543, for the Treatment of Myeloproliferative Neoplasms.

Honghe Wan1, Gretchen M Schroeder1, Amy C Hart1, Jennifer Inghrim1, James Grebinski1, John S Tokarski1, Matthew V Lorenzi1, Dan You1, Theresa Mcdevitt1, Becky Penhallow1, Ragini Vuppugalla1, Yueping Zhang1, Xiaomei Gu1, Ramaswamy Iyer1, Louis J Lombardo1, George L Trainor1, Stefan Ruepp1, Jonathan Lippy1, Yuval Blat1, John S Sack1, Javed A Khan1, Kevin Stefanski1, Bogdan Sleczka1, Arvind Mathur1, Jung-Hui Sun1, Michael K Wong1, Dauh-Rurng Wu1, Peng Li1, Anuradha Gupta1, P N Arunachalam1, Bala Pragalathan1, Sankara Narayanan1, Nanjundaswamy K C1, Prakasam Kuppusamy1, Ashok V Purandare1.   

Abstract

JAK2 kinase inhibitors are a promising new class of agents for the treatment of myeloproliferative neoplasms and have potential for the treatment of other diseases possessing a deregulated JAK2-STAT pathway. X-ray structure and ADME guided refinement of C-4 heterocycles to address metabolic liability present in dialkylthiazole 1 led to the discovery of a clinical candidate, BMS-911543 (11), with excellent kinome selectivity, in vivo PD activity, and safety profile.

Entities:  

Keywords:  BMS-911543; JAK2; myeloproliferative neoplasm; selective inhibitor; structure-guided design

Year:  2015        PMID： 26288683      PMCID： PMC4538448          DOI： 10.1021/acsmedchemlett.5b00226

Source DB:  PubMed          Journal:  ACS Med Chem Lett        ISSN： 1948-5875            Impact factor:   4.345


  18 in total

Review 1.  Optimization of metabolic stability as a goal of modern drug design.

Authors:  T N Thompson
Journal:  Med Res Rev       Date:  2001-09       Impact factor: 12.944

2.  A survey of cyclic replacements for the central diamide moiety of inhibitors of inosine monophosphate dehydrogenase.

Authors:  T G Murali Dhar; Chunjian Liu; William J Pitts; Junquing Guo; Scott H Watterson; Henry Gu; Catherine A Fleener; Katherine Rouleau; N Z Sherbina; Joel C Barrish; Diane Hollenbaugh; Edwin J Iwanowicz
Journal:  Bioorg Med Chem Lett       Date:  2002-11-04       Impact factor: 2.823

3.  TG101209, a small molecule JAK2-selective kinase inhibitor potently inhibits myeloproliferative disorder-associated JAK2V617F and MPLW515L/K mutations.

Authors:  A Pardanani; J Hood; T Lasho; R L Levine; M B Martin; G Noronha; C Finke; C C Mak; R Mesa; H Zhu; R Soll; D G Gilliland; A Tefferi
Journal:  Leukemia       Date:  2007-05-31       Impact factor: 11.528

4.  Three-year efficacy, safety, and survival findings from COMFORT-II, a phase 3 study comparing ruxolitinib with best available therapy for myelofibrosis.

Authors:  Francisco Cervantes; Alessandro M Vannucchi; Jean-Jacques Kiladjian; Haifa Kathrin Al-Ali; Andres Sirulnik; Viktoriya Stalbovskaya; Mari McQuitty; Deborah S Hunter; Richard S Levy; Francesco Passamonti; Tiziano Barbui; Giovanni Barosi; Claire N Harrison; Laurent Knoops; Heinz Gisslinger
Journal:  Blood       Date:  2013-10-30       Impact factor: 22.113

Review 5.  Investigational Janus kinase inhibitors.

Authors:  Constantine S Tam; Srdan Verstovsek
Journal:  Expert Opin Investig Drugs       Date:  2013-02-23       Impact factor: 6.206

Review 6.  Disordered signaling in myeloproliferative neoplasms.

Authors:  Shubha Anand; Brian J P Huntly
Journal:  Hematol Oncol Clin North Am       Date:  2012-08-25       Impact factor: 3.722

7.  Discovery of the macrocycle 11-(2-pyrrolidin-1-yl-ethoxy)-14,19-dioxa-5,7,26-triaza-tetracyclo[19.3.1.1(2,6).1(8,12)]heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene (SB1518), a potent Janus kinase 2/fms-like tyrosine kinase-3 (JAK2/FLT3) inhibitor for the treatment of myelofibrosis and lymphoma.

Authors:  Anthony D William; Angeline C-H Lee; Stéphanie Blanchard; Anders Poulsen; Ee Ling Teo; Harish Nagaraj; Evelyn Tan; Dizhong Chen; Meredith Williams; Eric T Sun; Kee Chuan Goh; Wai Chung Ong; Siok Kun Goh; Stefan Hart; Ramesh Jayaraman; Mohammed Khalid Pasha; Kantharaj Ethirajulu; Jeanette M Wood; Brian W Dymock
Journal:  J Med Chem       Date:  2011-06-15       Impact factor: 7.446

8.  In vitro metabolism and covalent binding of enol-carboxamide derivatives and anti-inflammatory agents sudoxicam and meloxicam: insights into the hepatotoxicity of sudoxicam.

Authors:  R Scott Obach; Amit S Kalgutkar; Tim F Ryder; Gregory S Walker
Journal:  Chem Res Toxicol       Date:  2008-08-16       Impact factor: 3.739

9.  Expression of Jak2V617F causes a polycythemia vera-like disease with associated myelofibrosis in a murine bone marrow transplant model.

Authors:  Gerlinde Wernig; Thomas Mercher; Rachel Okabe; Ross L Levine; Benjamin H Lee; D Gary Gilliland
Journal:  Blood       Date:  2006-02-14       Impact factor: 22.113

10.  Safety and efficacy of TG101348, a selective JAK2 inhibitor, in myelofibrosis.

Authors:  Animesh Pardanani; Jason R Gotlib; Catriona Jamieson; Jorge E Cortes; Moshe Talpaz; Richard M Stone; Michael H Silverman; D Gary Gilliland; Jolene Shorr; Ayalew Tefferi
Journal:  J Clin Oncol       Date:  2011-01-10       Impact factor: 44.544
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  4 in total

Review 1.  Evaluation of Substituted Pyrazole-Based Kinase Inhibitors in One Decade (2011-2020): Current Status and Future Prospects.

Authors:  Mohammed I El-Gamal; Seyed-Omar Zaraei; Moustafa M Madkour; Hanan S Anbar
Journal:  Molecules       Date:  2022-01-05       Impact factor: 4.411

2.  Structure-Based Design of Selective Janus Kinase 2 Imidazo[4,5-d]pyrrolo[2,3-b]pyridine Inhibitors.

Authors:  Amy C Hart; Gretchen M Schroeder; Honghe Wan; James Grebinski; Jennifer Inghrim; James Kempson; Junqing Guo; William J Pitts; John S Tokarski; John S Sack; Javed A Khan; Jonathan Lippy; Matthew V Lorenzi; Dan You; Theresa McDevitt; Ragini Vuppugalla; Yueping Zhang; Louis J Lombardo; George L Trainor; Ashok V Purandare
Journal:  ACS Med Chem Lett       Date:  2015-07-10       Impact factor: 4.345

Review 3.  Second-Generation Jak2 Inhibitors for Advanced Prostate Cancer: Are We Ready for Clinical Development?

Authors:  Paul Beinhoff; Lavannya Sabharwal; Vindhya Udhane; Cristina Maranto; Peter S LaViolette; Kenneth M Jacobsohn; Susan Tsai; Kenneth A Iczkowski; Liang Wang; William A Hall; Scott M Dehm; Deepak Kilari; Marja T Nevalainen
Journal:  Cancers (Basel)       Date:  2021-10-17       Impact factor: 6.575

4.  Discovery of novel JAK2 and EGFR inhibitors from a series of thiazole-based chalcone derivatives.

Authors:  Kamonpan Sanachai; Thitinan Aiebchun; Panupong Mahalapbutr; Supaphorn Seetaha; Lueacha Tabtimmai; Phornphimon Maitarad; Iakovos Xenikakis; Athina Geronikaki; Kiattawee Choowongkomon; Thanyada Rungrotmongkol
Journal:  RSC Med Chem       Date:  2021-02-26
  4 in total

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