Tropomyosin receptor kinase inhibitors: an updated patent review for 2016–2019

References

• Huang EJ, Reichardt LF. Neurotrophins: roles in neuronal development and function. Annu Rev Neurosci. 2001;24:677–736.
   PubMed Web of Science ®Google Scholar
• Bailey JJ, Schirrmacher R, Farrell K, et al. Tropomyosin receptor kinase inhibitors: an updated patent review for 2010–2016 – part I. Expert Opin Ther Pat. 2017;27(6):733–751.
   PubMed Web of Science ®Google Scholar
• Klein R, Jing SQ, Nanduri V, et al. The Trk protooncogene encodes a receptor for nerve growth-factor. Cell. 1991;65(1):189–197.
   PubMed Web of Science ®Google Scholar
• Kaplan DR, Martinzanca D, Parada LF. Tyrosine phosphorylation and tyrosine kinase-activity of the Trk protooncogene product induced by Ngf. Nature. 1991;350(6314):158–160.
   PubMed Web of Science ®Google Scholar
• Klein R, Nanduri V, Jing SQ, et al. The Trkb tyrosine protein-kinase is a receptor for brain-derived neurotrophic factor and neurotrophin-3. Cell. 1991;66(2):395–403.
   PubMed Web of Science ®Google Scholar
• Lamballe F, Klein R, Barbacid M. Trkc, a new member of the Trk family of tyrosine protein-kinases, is a receptor for neurotrophin-3. Cell. 1991;66(5):967–979.
   PubMed Web of Science ®Google Scholar
• Siniscalco D, Giordano C, Rossi F, et al. Role of neurotrophins in neuropathic pain. Curr Neuropharmacol. 2011;9(4):523–529.
   PubMed Web of Science ®Google Scholar
• Gupta VK, You YY, Gupta VB, et al. TrkB receptor signalling: implications in neurodegenerative, psychiatric and proliferative disorders. Int J Mol Sci. 2013;14(5):10122–10142.
   PubMed Web of Science ®Google Scholar
• Vaishnavi A, Le AT, Doebele RC. TRKing down an old oncogene in a new era of targeted therapy. Cancer Discov. 2015;5(1):25–34.
   PubMed Web of Science ®Google Scholar
• Amatu A, Sartore-Bianchi A, Siena S. NTRK gene fusions as novel targets of cancer therapy across multiple tumour types. Esmo Open. 2016;1:2.
   Web of Science ®Google Scholar
• Stransky N, Cerami E, Schalm S, et al. The landscape of kinase fusions in cancer. Nat Commun. 2014;5:4846.
   Web of Science ®Google Scholar
• Vaishnavi A, Capelletti M, Le AT, et al. Oncogenic and drug-sensitive NTRK1 rearrangements in lung cancer. Nat Med. 2013;19(11):1469–1472.
   PubMed Web of Science ®Google Scholar
• Martinzanca D, Hughes SH, Barbacid M. A human oncogene formed by the fusion of truncated tropomyosin and protein tyrosine kinase sequences. Nature. 1986;319(6056):743–748.
   PubMed Web of Science ®Google Scholar
• Ardini E, Bosotti R, Borgia AL, et al. The TPM3-NTRK1 rearrangement is a recurring event in colorectal carcinoma and is associated with tumor sensitivity to TRKA kinase inhibition. Mol Oncol. 2014;8(8):1495–1507.
   PubMed Web of Science ®Google Scholar
• Tacconelli A, Farina AR, Cappabianca L, et al. TrkAIII - A novel hypoxia-regulated alternative TrkA splice variant of potential physiological and pathological importance. Cell Cycle. 2005;4(1):8–9.
   PubMed Web of Science ®Google Scholar
• Greco A, Miranda C, Pierotti MA. Rearrangements of NTRK1 gene in papillary thyroid carcinoma. Mol Cell Endocrinol. 2010;321(1):44–49.
   PubMed Web of Science ®Google Scholar
• Kralik JM, Kranewitter W, Boesmueller H, et al. Characterization of a newly identified ETV6-NTRK3 fusion transcript in acute myeloid leukemia. Diagn Pathol. 2011;6:19.
   Web of Science ®Google Scholar
• Frattini V, Trifonov V, Chan JM, et al. The integrated landscape of driver genomic alterations in glioblastoma. Nat Genet. 2013;45(10):1141–1149.
   PubMed Web of Science ®Google Scholar
• Doebele RC, Dziadziuszko R, Drilon A, et al. Genomic landscape of entrectinib resistance from ctDNA analysis in STARTRK-2. Ann Oncol. 2019;30:Supplement_5.
   Web of Science ®Google Scholar
• Drilon A, Laetsch TW, Kummar S, et al. Efficacy of larotrectinib in TRK fusion–positive cancers in adults and children. N Engl J Med. 2018;378(8):731–739.
   PubMed Web of Science ®Google Scholar
• Drilon A, Nagasubramanian R, Blake JF, et al. A next-generation TRK kinase inhibitor overcomes acquired resistance to prior TRK kinase inhibition in patients with TRK fusion-positive solid tumors. Cancer Discov. 2017;7(9):963–972.
   PubMed Web of Science ®Google Scholar
• Russo M, Misale S, Wei G, et al. Acquired resistance to the TRK inhibitor entrectinib in colorectal cancer. Cancer Discov. 2016;6(1):36–44.
   PubMed Web of Science ®Google Scholar
• Awad MM, Katayama R, McTigue M, et al. Acquired resistance to crizotinib from a mutation in CD74–ROS1. N Engl J Med. 2013;368(25):2395–2401.
   PubMed Web of Science ®Google Scholar
• Gainor JF, Dardaei L, Yoda S, et al. Molecular mechanisms of resistance to first- and second-generation ALK inhibitors in ALK-rearranged lung cancer. Cancer Discov. 2016;6(10):1118–1133.
   PubMed Web of Science ®Google Scholar
• Sakamoto H, Tsukaguchi T, Hiroshima S, et al. CH5424802, a selective ALK inhibitor capable of blocking the resistant gatekeeper mutant. Cancer Cell. 2011;19(5):679–690.
   PubMed Web of Science ®Google Scholar
• Marsilje TH, Pei W, Chen B, et al. Synthesis, structure–activity relationships, and in vivo efficacy of the novel potent and selective anaplastic lymphoma kinase (ALK) inhibitor 5-chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine (LDK378) currently in phase 1 and phase 2 clinical trials. J Med Chem. 2013;56(14):5675–5690.
   PubMed Web of Science ®Google Scholar
• Zou HY, Li Q, Engstrom LD, et al. PF-06463922 is a potent and selective next-generation ROS1/ALK inhibitor capable of blocking crizotinib-resistant ROS1 mutations. Proc Nat Acad Sci. 2015;112(11):3493–3498.
   PubMed Web of Science ®Google Scholar
• Bailey JJ, Schirrmacher R, Farrell K, et al. Tropomyosin receptor kinase inhibitors: an updated patent review for 2010–2016-part II. Expert Opin Ther Pat. 2017;27(7):831–849.
   PubMed Web of Science ®Google Scholar
• Demetri GD, Paz-Ares L, Farago AF, et al. Efficacy and safety of entrectinib in patients with NTRK fusion-positive tumours: pooled analysis of STARTRK-2, STARTRK-1, and ALKA-372-001. Ann Oncol. 2018;29(suppl_8)viii713.
   Google Scholar
• Rolfo C, Dziadziuszko R, Doebele RC, et al. Updated efficacy and safety of entrectinib in patients with NTRK fusion-positive tumours: integrated analysis of STARTRK-2, STARTRK-1 and ALKA-372-001. Ann Oncol. 2019;30(suppl_5):v180.
   Google Scholar
• Robinson GW, Gajjar AJ, Gauvain KM, et al. Phase 1/1B trial to assess the activity of entrectinib in children and adolescents with recurrent or refractory solid tumors including central nervous system (CNS) tumors. J clin oncol. 2019;37(15_suppl): 10009–09.
   PubMed Web of Science ®Google Scholar
• Krämer A, Losa F, Gay LM, et al. Comprehensive profiling and molecularly guided therapy (MGT) for carcinomas of unknown primary (CUP): CUPISCO: a phase II, randomised, multicentre study comparing targeted therapy or immunotherapy with standard platinum-based chemotherapy. Ann Oncol. 2018;29(suppl_8):viii133–viii48.
   Google Scholar
• Hyman DM, van Tilburg CM, Albert CM, et al. Durability of response with larotrectinib in adult and pediatric patients with TRK fusion cancer. Ann Oncol. 2019;30(Supplement_5):v162-v163.
   Google Scholar
• Hyman D, Kummar S, Farago A, et al. Phase I and expanded access experience of LOXO-195 (BAY 2731954), a selective next-generation TRK inhibitor (TRKi). Cancer Res. 2019;79:13.
   Google Scholar
• Cho BC, Drilon AE, Doebele RC, et al. Safety and preliminary clinical activity of repotrectinib in patients with advanced ROS1 fusion-positive non-small cell lung cancer (TRIDENT-1 study). J clin oncol. 2019;37(15_suppl): 9011–11.
   Web of Science ®Google Scholar
• Papadopoulos KP, Gandhi L, Janne PA, et al. First-in-human study of DS-6051b in patients (pts) with advanced solid tumors (AST) conducted in the US. J clin oncol. 2018;36(15_suppl): 2514–14.
   Google Scholar
• Fujiwara Y, Takeda M, Yamamoto N, et al. Safety and pharmacokinetics of DS-6051b in Japanese patients with non-small cell lung cancer harboring ROS1 fusions: a phase I study. Oncotarget. 2018;9(34):23729–23737.
   PubMedGoogle Scholar
• Katayama R, Gong B, Togashi N, et al. The new-generation selective ROS1/NTRK inhibitor DS-6051b overcomes crizotinib resistant ROS1-G2032R mutation in preclinical models. Nat Commun. 2019;10(1):3604.
   PubMedGoogle Scholar
• Kim M, Lee C, Lee G, et al. Fused ring heteroaryl compounds and their use as trk inhibitors. WO2016097869. 2016.
   Google Scholar
• Drilon A, Hofmann N, Flynn D, et al. The type II switch control kinase inhibitor, DCC-2701 (altiratinib) effectively inhibits resistant NTRK kinase domain mutants. Eur J Cancer. 2016;69:S138.
   Web of Science ®Google Scholar
• Werner T, Heist R, Carvajal R, et al. P2.06-001 A study of MGCD516, a receptor tyrosine kinase (RTK) inhibitor, in molecularly selected patients with NSCLC or other advanced solid tumors: topic: phase i trials. J Thorac Oncol. 2017;12(1):S1068–S69.
   Web of Science ®Google Scholar
• Konicek BW, Capen AR, Credille KM, et al. Merestinib (LY2801653) inhibits neurotrophic receptor kinase (NTRK) and suppresses growth of NTRK fusion bearing tumors. Oncotarget. 2018;9(17):13796–13806.
   PubMedGoogle Scholar
• Besse B, Garassino MC, Rajan A, et al. Efficacy of milciclib (PHA-848125AC), a pan-cyclin d-dependent kinase inhibitor, in two phase II studies with thymic carcinoma (TC) and B3 thymoma (B3T) patients. J clin oncol. 2018;36(15_suppl): 8519–19.
   PubMed Web of Science ®Google Scholar
• Lin -C-C, Arkenau H-T, Lu S, et al. A phase 1, open-label, dose-escalation trial of oral TSR-011 in patients with advanced solid tumours and lymphomas. Br J Cancer. 2019;121(2):131–138.
   PubMed Web of Science ®Google Scholar
• Mantyh PW, Koltzenburg M, Mendell LM, et al. Antagonism of nerve growth factor-TrkA signaling and the relief of pain. Anesthesiology. 2011;115(1):189–204.
   PubMed Web of Science ®Google Scholar
• Roblin D, Yosipovitch G, Boyce B, et al. Topical TrkA kinase inhibitor CT327 is an effective, novel therapy for the treatment of pruritus due to psoriasis: results from experimental studies, and efficacy and safety of CT327 in a phase 2b clinical trial in patients with psoriasis. Acta Derm Venereol. 2015;95(5):542–548.
   PubMed Web of Science ®Google Scholar
• Danilenko M, Stamp E, Stocken DD, et al. Targeting tropomyosin receptor kinase in cutaneous CYLD defective tumors with pegcantratinib: the TRAC randomized clinical trial. JAMA Dermatol. 2018;154(8):913–921.
   PubMed Web of Science ®Google Scholar
• Krupka E, Jiang GL, Jan C. Efficacy and safety of intra-articular injection of tropomyosin receptor kinase a inhibitor in painful knee osteoarthritis: a randomized, double-blind and placebo-controlled study. Osteoarthritis Cartilage. 2019;27(11):1599–1607.
   PubMed Web of Science ®Google Scholar
• Watt FE, Blauwet MB, Fakhoury A, et al. Tropomyosin-related kinase a (TrkA) inhibition for the treatment of painful knee osteoarthritis: results from a randomized controlled phase 2a trial. Osteoarthritis Cartilage. 2019;27(11):1590–1598.
   PubMed Web of Science ®Google Scholar
• Ishiguro N, Oyama S, Higashi R, et al. Efficacy, safety, and tolerability of ONO-4474, an orally available pan-tropomyosin receptor kinase inhibitor, in Japanese patients with moderate to severe osteoarthritis of the knee: a randomized, placebo-controlled, double-blind, parallel-group comparative study. J Clin Pharmacol. 2020;60(1):28–36.
   PubMed Web of Science ®Google Scholar
• Chung V, Wang L, Fletcher MS, et al. First-time in-human study of VMD-928, an allosteric and irreversible TrkA selective inhibitor, in patients with solid tumors or lymphoma. J clin oncol. 2019;37(15_suppl):TPS3146–TPS46.
   Web of Science ®Google Scholar
• Wu JJ-Q, Wang L Compositions of protein receptor tyrosine kinase inhibitors. WO2010077680. 2010.
   Google Scholar
• Kong NX, Zhou C, Zheng Z Heterocyclic compound which acts as trk inhibitor. WO2019157879. 2019.
   Google Scholar
• Turk S, Merget B, Eid S, et al. From cancer to pain target by automated selectivity inversion of a clinical candidate. J Med Chem. 2018;61(11):4851–4859.
   PubMed Web of Science ®Google Scholar
• Eid S, Fulle S, Merget B, et al. Pyrimidine derivatives as tropomyosin receptor kinase a (trka) inhibitors. WO2019101843. 2019.
   Google Scholar
• Wenglowsky SM, Brooijmans N, Miduturu CV, et al. Compounds and compositions useful for treating disorders related to ntrk. WO2017035354. 2017.
   Google Scholar
• Wenglowsky SM, Miduturu CV, Bitfulco N, et al. Compounds and compositions useful for treating disorders related to ntrk. WO2017087778. 2017.
   Google Scholar
• Zhu L, Hu Y, Wu W, et al. Amino pyrazolopyrimidine compound used as a neurotrophic factor tyrosine kinase receptor inhibitor. WO2018077246. 2018.
   Google Scholar
• Tomizawa M, Nishi H, Tanaka H, et al. Dihydronaphtho[2,3-b]benzofuran derivative. WO2017073706. 2017.
   Google Scholar
• Kinoshita K, Asoh K, Furuichi N, et al. Tetracyclic compound. WO2010143664. 2010.
   Google Scholar
• Tanaka H, Sase H, Tsukaguchi T, et al. Selective TRK inhibitor CH7057288 against TRK fusion-driven cancer. Mol Cancer Ther. 2018;17(12):2519–2529.
   PubMed Web of Science ®Google Scholar
• Liu H, Tan H, He C, et al. Substituted (2-azabicyclo [3.1.0] hexan-2-yl) pyrazolo [1, 5-a] pyrimidine and imidazo [1, 2-b] pyridazine compounds as trk kinases inhibitors. WO2019174598. 2019.
   Google Scholar
• Nagaswamy K, Tirunagaru V. Inhibitors of trka kinase WO2016116900. 2016.
   Google Scholar
• Li J, Zhang D, Wang Z, et al. Imidazo[1,2-b]pyridazine macrocyclic kinase inhibitor. WO2019120267. 2019.
   Google Scholar
• Nanda N, Bilenker JH, Doebele RC, et al. Point mutations in trk inhibitor-resistant cancer and methods relating to the same. WO2017075107. 2017.
   Google Scholar
• Bilenker JH, Naarden JV, Nanda N Treatment of trk-associated cancers. WO2019191659. 2019.
   Google Scholar
• Chakravarty S, Rai R, Green MJ, et al. Fused cycloalkyl-pyrimidine compounds and uses thereof. WO2016003827. 2016.
   Google Scholar
• Wang J, Sun J, Zhu W, et al. Pyrazolopyrimidine derivative and use thereof. WO2019165967. 2019.
   Google Scholar
• Tanaka F, Nagasue H, Kawada Y, et al. Novel tetrahydronaphthyl urea derivatives. WO2018199166. 2018.
   Google Scholar
• Kawada Y, Saitoh F, Nagasue H, et al. Crystals of tetrahydronaphthyl urea derivative. WO2019054451. 2019.
   Google Scholar
• Kozaki R, Yoshizawa T, Tsukamoto K, et al. Abstract 2954A: a potent and selective TRK inhibitor ONO-5390556, shows potent antitumor activity against both TRK-rearranged cancers and the resistant mutants. Cancer Res. 2016;76(14Supplement):2954A–54A.
   PubMedGoogle Scholar
• Tsukamoto K, Yoshizawa T, Kozaki R, et al. Abstract 788: a novel, potent and selective pan-Trk inhibitor ONO-5390556, demonstrates therapeutic efficacy in cancer cells harboring the TrkA rearrangement. Cancer Res. 2015;75(15 Supplement): 788–88.
   Google Scholar
• Kozaki R, Tsukamoto K, Egashira H, et al. Therapeutic agent for Trk inhibitor-resistant cancer. WO2017155018. 2017.
   Google Scholar
• Kozaki R, Kato H Method for treating cancer by combination of Trk inhibitor and kinase inhibitor. WO2019049891. 2019.
   Google Scholar
• Pal K, Ciblat S, Albert V, et al. 5-(2-(2,5-difluorophenyl)pyrrolidin-1 -yl)-3-(1h-pyrazol-1-yl)pyrazolo[1,5-a]pyrimidine derivatives and related compounds as trk kinase inhibitors for treating cancer. WO2019118584. 2019.
   Google Scholar
• Regina A, Elagoz A, Albert V, et al. Abstract 2198: PBI-200: a novel, brain penetrant, next generation pan-TRK kinase inhibitor. Cancer Res. 2019;79(13 Supplement): 2198–98.
   Web of Science ®Google Scholar
• Lin J, Ying Y, Liao J, et al. Compound having macrocyclic molecular structure and use thereof. WO2019149131. 2019.
   Google Scholar
• Wang Y, Zhao J. Substituted pyrazolo[1,5-a]pyrimidine macrocyclic compound. WO2019144885. 2019.
   Google Scholar
• Wang Y, Zhao J, Al Y. Di(hetero)aryl macrocyclic compound for inhibiting protein kinase activity. WO2019201131. 2019.
   Google Scholar
• Yukimasa A, Kano K, Horiguchi T, et al. Nitrogen-containing heterocycle having trka inhibitory activity, and carbocyclic derivative. WO2017135399. 2017.
   Google Scholar
• Yukimasa A, Kozono I, Nakamura K, et al. Heterocyclic and carbocyclic derivative having trka-inhibiting activity. WO2016021629. 2016.
   Google Scholar
• Kano K, Yamaguchi H, Horiguchi T, et al. Fused heterocycle having trka inhibitory activity and fused carbocycle derivative. WO2018079759. 2018.
   Google Scholar
• Traversa S, Bagnod R, Mainero V, et al. Reducing exposure conjugates modulating therapeutic targets. WO2018175340. 2018.
   Google Scholar
• Traversa S, Mainero V, Bagnod R, et al. Uses of polymer conjugates of indolocarbazole compounds with reduced exposure. WO2018208369. 2018.
   Google Scholar
• Traversa S, Harris TJ, Mainero V, et al. Polymer conjugates of staurosporine derivatives having reduced exposure. WO2018175315. 2018.
   Google Scholar
• Drilon A, Ou S-HI, Cho BC, et al. Repotrectinib (TPX-0005) is a next-generation ROS1/TRK/ALK inhibitor that potently inhibits ROS1/TRK/ALK solvent- front mutations. Cancer Discov. 2018;8(10):1227–1236.
   PubMed Web of Science ®Google Scholar
• Cui JJ, Li Y, Rogers EW, et al. Diaryl macrocycles as modulators of protein kinases. WO2015112806. 2015.
   Google Scholar
• Cui JJ, Li Y, Rogers EW, et al. Macrocycle kinase inhibitors. WO2018022911. 2018.
   Google Scholar
• Rogers EW, Cui JJ, Zhai D, et al. Macrocyclic compounds for treating disease. WO2019126121. 2019.
   Google Scholar
• Rogers EW, Ung J, Zhang H, et al. Macrocyclic kinase inhibitors and their use. WO2019126122. 2019.
   Google Scholar
• Chen Y, Chi P. Basket trial of TRK inhibitors demonstrates efficacy in TRK fusion-positive ca\ncers. J Hematol Oncol. 2018;11:78.
   PubMed Web of Science ®Google Scholar
• Bagal SK, Omoto K, Blakemore DC, et al. Discovery of allosteric, potent, subtype selective, and peripherally restricted TrkA kinase inhibitors. J Med Chem. 2019;62(1):247–265.
   PubMed Web of Science ®Google Scholar