FAK inhibitors in Cancer, a patent review

References

• Zhang J, Hochwald SN. The role of FAK in tumor metabolism and therapy. Pharmacol Ther. 2014;142:154−163.
   PubMed Web of Science ®Google Scholar
• Lechertier T, Hodivala-Dilke K. Focal adhesion kinase and tumor angiogenesis. J Pathol. 2012;226:404−412.
   PubMed Web of Science ®Google Scholar
• Ma WW. Development of focal adhesion kinase inhibitors in cancer therapy. Anticancer Agents Med Chem. 2011;11:638−642.
   PubMed Web of Science ®Google Scholar
• Fletcher DA, Mullins RD. Cell mechanics and the cytoskeleton. Nature. 2010;463:485–492.
   PubMed Web of Science ®Google Scholar
• Frame MC, Patel H, Serrels B, et al. The FERM domain: organizing the structure and function of FAK. Nat Rev Mol Cell Biol. 2010;11:802–814.
   PubMed Web of Science ®Google Scholar
• Zhao J, Guan JL. Signal transduction by focal adhesion kinase in cancer. Cancer Metastasis Rev. 2009;28:35–49.
   PubMed Web of Science ®Google Scholar
• Golubovskaya VM. Focal adhesion kinase as a cancer therapy target. Anticancer Agents Med Chem. 2010;10:735–741.
   PubMed Web of Science ®Google Scholar
• Schwock J, Dhani N, Hedley DW. Targeting focal adhesion kinase signaling in tumor growth and metastasis. Expert Opin Ther Targets. 2010;14:77–94.
   PubMed Web of Science ®Google Scholar
• Schultze A, Fiedlerw. Therapeutic potential and limitations of new FAK inhibitors in the treatment of cancer. Expert Opin Investig Drugs. 2010;19:777–788.
   PubMed Web of Science ®Google Scholar
• Cabrita MA, Jones LM, Quizi JL, et al. Focal adhesion kinase inhibitors are potent anti-angiogenic agents. Mol Oncol. 2011;5:517–526.
   PubMed Web of Science ®Google Scholar
• Schultze A, Decker S, Otten J, et al. TAE226-mediated inhibition of focal adhesion kinase interferes with tumor angiogenesis and vasculogenesis. Invest New Drugs. 2010;28:825–833.
   PubMed Web of Science ®Google Scholar
• Van Nimwegen MJ, Verkoeijen S, Van Buren L, et al. Requirement for focal adhesion kinase in the early phase of mammary adenocarcinoma lung metastasis formation. Cancer Res. 2005;65:4698–4706.
   PubMed Web of Science ®Google Scholar
• Lim ST, Miller NL, Chen XL, et al. Nuclear-localized focal adhesion kinase regulates inflammatory VCAM-1 expression. J Cell Biol. 2012;197(7):907–919.
   PubMed Web of Science ®Google Scholar
• Serrels A, Lund T, Serrels B, et al. Nuclear FAK controls chemokine transcription, Tregs, and evasion of anti-tumor immunity. Cell. 2015;163(1):160–173.
   PubMed Web of Science ®Google Scholar
• Parsons JT. Focal adhesion kinase: the first ten years. J Cell Sci. 2003;116:1409–1416.
   PubMed Web of Science ®Google Scholar
• Mitra SK, Hanson DA, Schlaepfer DD. Focal adhesion kinase: in command and control of cell motility. Nat Rev Mol Cell Biol. 2005;6:56–68.
   PubMed Web of Science ®Google Scholar
• Schaller MD. Cellular functions of FAK kinases: insight into molecular mechanisms and novel functions. J Cell Sci. 2010;123:1007–1013.
   PubMed Web of Science ®Google Scholar
• Weiner TM, Liu ET, Craven RJ, et al. Expression of focal adhesion kinase gene and invasive cancer. The Lancet. 1993;342:1024–1025.
   PubMed Web of Science ®Google Scholar
• Tremblay L, Hauck W, Aprikian AG, et al. Focal adhesion kinase (pp125 FAK) expression, activation and association with paxillin and p50 CSK in human metastatic prostate carcinoma. International Journal of Cancer. 1996;68(2):164–171.
   PubMed Web of Science ®Google Scholar
• Judson PL, He X, Cance WG, et al. Overexpression of focal adhesion kinase, a protein tyrosine kinase, in ovarian carcinoma. Cancer. 1999;86(8):1551–1556.
   PubMed Web of Science ®Google Scholar
• Lark AL, Livasy CA, Calvo B, et al. Overexpression of focal adhesion kinase in primary colorectal carcinomas and colorectal liver metastases: immunohistochemistry and realtime PCR analyses. Clinical Cancer Research. 2003;9(1):215–222.
   PubMed Web of Science ®Google Scholar
• Xu Q, Pachter JA, Tam W. Methods and compositions for treating abnormal cell growth (e.g., cancer) using FAK inhibitor and a MEK inhibitor. From PCT Int Appl. 2015;WO 2015120289 A1 20150813.
   Google Scholar
• Agochiya M, Brunton VG, Owens DW, et al. Increased dosage and amplification of the focal adhesion kinase gene in human cancer cells. Oncogene. 1999;18(41):5646–5653.
   PubMed Web of Science ®Google Scholar
• Canel M, Secades P, Rodrigoet JP, et al. Overexpression of focal adhesion kinase in head and neck squamous cell carcinoma is independent of fak gene copy number. Clinical Cancer Research. 2006;12(11):3272–3279.
   PubMed Web of Science ®Google Scholar
• Ott GR, Cheng M, Learn KS, et al. Discovery of clinical candidate CEP-37440, a selective inhibitor of focal adhesion kinase (FAK) and anaplastic lymphoma kinase (ALK). J Med Chem. 2016;59:7478–7496.
   PubMed Web of Science ®Google Scholar
• Dao P, Smith N, Tomkiewicz-Raulet C, et al. Design, synthesis, and evaluation of novel imidazo[1,2‑a][1,3,5]triazines and their derivatives as focal adhesion kinase inhibitors with antitumor activity. J Med Chem. 2015;58:237–251.
   PubMedGoogle Scholar
• Qu M, Liu Z, Zhao D, et al. Design, synthesis and biological evaluation of sulfonamide-substituted diphenylpyrimidine derivatives (Sul-DPPYs) as potent focal adhesion kinase (FAK) inhibitors with antitumor activity. Bioorg Med Chem. 2017;25:3989–3996.
   PubMed Web of Science ®Google Scholar
• Dao P, Lietha D, Etheve-Quelquejeu M, et al. Synthesis of novel 1,2,4-triazine scaffold as FAK inhibitors with antitumor activity. Bioorg Med Chem Lett. 2017;27:1727–1730.
   PubMed Web of Science ®Google Scholar
• Schlaepfer DD, Hauck CR, Sieg DJ. Signaling through focal adhesion kinase. Prog Biophys Mol Biol. 1999;71:435.
   PubMed Web of Science ®Google Scholar
• Xing L, Rai B, Lunney EA. Scaffold mining of kinase hinge binders in crystal structure database. J Comput Aided Mol Des. 2014;28:13.
   PubMed Web of Science ®Google Scholar
• Buckbinder L, Crawford DT, Qi H, et al. Proline-rich tyrosine kinase 2 regulates osteoprogenitor cells and bone formation, and offers an anabolic treatment approach for osteoporosis. Proc Natl Acad Sci USA. 2007;104:10619.
   PubMed Web of Science ®Google Scholar
• Walker DP, Bi FC, Kalgutkar AS, et al. Trifluoromethylpyrimidine-based inhibitors of proline-rich tyrosine kinase 2 (PYK2): structure-activity relationships and strategies for the elimination of reactive metabolite formation. Bioorg Med Chem Lett. 2008;18:6071.
   PubMed Web of Science ®Google Scholar
• Han S, Mistry A, Chang JS, et al. Structural characterization of proline-rich tyrosine kinase 2 (PYK2) reveals a unique (DFG-out) conformation and enables inhibitor design. J Biol Chem. 2009;284:13193.
   PubMed Web of Science ®Google Scholar
• Roberts WG, Ung E, Whalen P, et al. Antitumor activity and pharmacology of a selective focal adhesion kinase inhibitor, PF-562,271. Cancer Res. 2008;68:1935.
   PubMed Web of Science ®Google Scholar
• Walker DP, Zawistoski MP, McGlynn MA, et al. Sulfoximine-substituted trifluoromethylpyrimidine analogs as inhibitors of proline-rich tyrosine kinase 2 (PYK2) show reduced hERG activity. Bioorg Med Chem Lett. 2009;19:3253.
   PubMed Web of Science ®Google Scholar
• Farand J, Mai N, Chandrasekhar J, et al. Selectivity switch between FAK and Pyk2: macrocyclization of FAK inhibitors improves Pyk2 potency. Bioorg Med Chem Lett. 2016;26:5926.
   PubMed Web of Science ®Google Scholar
• [Cited 2017 Dec 09]. https://clinicaltrials.gov/ct2/show/NCT01951690
   Google Scholar
• Jiang H, Hegde S, Knolhoff BL, et al. Targeting focal adhesion kinase renders pancreatic cancers responsive to checkpoint immunotherapy. Nat Med. 2016;22(8):851–860.
   PubMed Web of Science ®Google Scholar
• Canel M, Byron A, Sims AH, et al. Nuclear FAK and runx1 cooperate to regulate IGFBP3, cell-cycle progression, and tumor growth. Cancer Res. 2017;77(19):5301–5312.
   PubMed Web of Science ®Google Scholar
• Schoenherr C, Byron A, Sandilands E, et al. Ambra1 spatially regulates SRC activity and SRC/FAK-mediated cancer cell invasion via trafficking networks. Elife. 2017;6:pii: e23172.
   PubMed Web of Science ®Google Scholar
• Serrels A, Frame MC. FAK goes nuclear to control antitumor immunity-a new target in cancer immuno-therapy. Oncoimmunology. 2016;5(4):e1119356.
   PubMed Web of Science ®Google Scholar
• Pachter JA, Ring JE, Weaver DT, et al. Treating cancer by combination of a FAK inhibitor and an immunotherapeutic agent, particular, an immune checkpoint inhibitor. PCT Int Appl. 2017;WO 2017004192 A1 20170105.
   Google Scholar
• [Cited 2017 Dec 09]. https://clinicaltrials.gov/ct2/show/NCT02523014
   Google Scholar
• Tomita N, Hayashi Y, Suzuki S, et al. Structure-based discovery of cellular-active allosteric inhibitors of FAK. Bioorg Med Chem Lett. 2013;23(6):1779–1785.
   PubMed Web of Science ®Google Scholar
• Iwatani M, Iwata H, Okabe A, et al. Discovery and characterization of novel allosteric FAK inhibitors. Eur J Med Chem. 2013;61:49–60.
   PubMed Web of Science ®Google Scholar