4l7s › Citations

Identification of a Novel and Selective Series of Itk Inhibitors via a Template-Hopping Strategy.

Alder CM, Ambler M, Campbell AJ, Champigny AC, Deakin AM, Harling JD, Harris CA, Longstaff T, Lynn S, Maxwell AC, Mooney CJ, Scullion C, Singh OM, Smith IE, Somers DO, Tame CJ, Wayne G, Wilson C, Woolven JM
ACS Med Chem Lett 4 948-52 (2013)
Cited: 11 times
EuropePMC logo PMID: 24900590

Abstract

Inhibition of Itk potentially constitutes a novel, nonsteroidal treatment for asthma and other T-cell mediated diseases. In-house kinase cross-screening resulted in the identification of an aminopyrazole-based series of Itk inhibitors. Initial work on this series highlighted selectivity issues with several other kinases, particularly AurA and AurB. A template-hopping strategy was used to identify a series of aminobenzothiazole Itk inhibitors, which utilized an inherently more selective hinge binding motif. Crystallography and modeling were used to rationalize the observed selectivity. Initial exploration of the SAR around this series identified potent Itk inhibitors in both enzyme and cellular assays.

Articles - 4l7s mentioned but not cited (2)

  1. Identification of inactive conformation-selective interleukin-2-inducible T-cell kinase (ITK) inhibitors based on second-harmonic generation. Hantani Y, Iio K, Hantani R, Umetani K, Sato T, Young T, Connell K, Kintz S, Salafsky J. FEBS Open Bio 8 1412-1423 (2018)
  2. Conformational Selectivity of ITK Inhibitors: Insights from Molecular Dynamics Simulations. Ogawa N, Ohta M, Ikeguchi M. J Chem Inf Model 63 7860-7872 (2023)


Reviews citing this publication (3)

  1. Ibrutinib-A double-edge sword in cancer and autoimmune disorders. Kokhaei P, Jadidi-Niaragh F, Sotoodeh Jahromi A, Osterborg A, Mellstedt H, Hojjat-Farsangi M. J Drug Target 24 373-385 (2016)
  2. Structure-based molecular modeling in SAR analysis and lead optimization. Temml V, Kutil Z. Comput Struct Biotechnol J 19 1431-1444 (2021)
  3. Inducible tyrosine kinase inhibitors: a review of the patent literature (2010 - 2013). Norman P. Expert Opin Ther Pat 24 979-991 (2014)

Articles citing this publication (6)

  1. Targeting interleukin-2-inducible T-cell kinase (ITK) and resting lymphocyte kinase (RLK) using a novel covalent inhibitor PRN694. Zhong Y, Dong S, Strattan E, Ren L, Butchar JP, Thornton K, Mishra A, Porcu P, Bradshaw JM, Bisconte A, Owens TD, Verner E, Brameld KA, Funk JO, Hill RJ, Johnson AJ, Dubovsky JA. J Biol Chem 290 5960-5978 (2015)
  2. Discovery of novel irreversible inhibitors of interleukin (IL)-2-inducible tyrosine kinase (Itk) by targeting cysteine 442 in the ATP pocket. Harling JD, Deakin AM, Campos S, Grimley R, Chaudry L, Nye C, Polyakova O, Bessant CM, Barton N, Somers D, Barrett J, Graves RH, Hanns L, Kerr WJ, Solari R. J Biol Chem 288 28195-28206 (2013)
  3. Synthesis of aminopyrazole analogs and their evaluation as CDK inhibitors for cancer therapy. Rana S, Sonawane YA, Taylor MA, Kizhake S, Zahid M, Natarajan A. Bioorg Med Chem Lett 28 3736-3740 (2018)
  4. Discovery and optimization of indazoles as potent and selective interleukin-2 inducible T cell kinase (ITK) inhibitors. Pastor RM, Burch JD, Magnuson S, Ortwine DF, Chen Y, De La Torre K, Ding X, Eigenbrot C, Johnson A, Liimatta M, Liu Y, Shia S, Wang X, Wu LC, Pei Z. Bioorg Med Chem Lett 24 2448-2452 (2014)
  5. Targeting SLP76:ITK interaction separates GVHD from GVL in allo-HSCT. Mammadli M, Huang W, Harris R, Xiong H, Weeks S, May A, Gentile T, Henty-Ridilla J, Waickman AT, August A, Bah A, Karimi M. iScience 24 102286 (2021)
  6. Design, synthesis and structure-activity relationships of a novel class of sulfonylpyridine inhibitors of Interleukin-2 inducible T-cell kinase (ITK). Trani G, Barker JJ, Bromidge SM, Brookfield FA, Burch JD, Chen Y, Eigenbrot C, Heifetz A, Ismaili MHA, Johnson A, Krülle TM, MacKinnon CH, Maghames R, McEwan PA, Montalbetti CAGN, Ortwine DF, Pérez-Fuertes Y, Vaidya DG, Wang X, Zarrin AA, Pei Z. Bioorg Med Chem Lett 24 5818-5823 (2014)


Quick links