189
Views
0
CrossRef citations to date
0
Altmetric
Review

Type I inhibitors of tropomyosin receptor kinase (Trk): a 2020–2022 patent update

, , ORCID Icon, ORCID Icon, , ORCID Icon & ORCID Icon show all
Pages 503-521 | Received 28 Jun 2023, Accepted 19 Sep 2023, Published online: 16 Oct 2023

References

  • Kojadinovic A, Laderian B, Mundi PS. Targeting TRK: a fast-tracked application of precision oncology and future directions. Crit Rev Oncol Hematol. 2021;165:103451. doi: 10.1016/j.critrevonc.2021.103451
  • 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. doi: 10.1158/2159-8290.CD-15-0940
  • Drilon A, Li G, Dogan S, et al. What hides behind the MASC: clinical response and acquired resistance to entrectinib after ETV6-NTRK3 identification in a mammary analogue secretory carcinoma (MASC). Ann Oncol. 2016;27(5):920–926. doi: 10.1093/annonc/mdw042
  • 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. doi: 10.1056/NEJMoa1714448
  • 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. doi: 10.1158/2159-8290.CD-17-0507
  • Drilon A, S-HI O, 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. doi: 10.1158/2159-8290.CD-18-0484
  • Huang EJ, Reichardt LF. Neurotrophins: roles in neuronal development and function. Annu Rev Neurosci. 2001;24:677–736. doi: 10.1146/annurev.neuro.24.1.677
  • 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. doi: 10.1158/2159-8290.CD-14-0765
  • Bertrand T, Kothe M, Liu J, et al. The crystal structures of TrkA and TrkB suggest key regions for achieving selective inhibition. J Mol Biol. 2012;423(3):439–453. doi: 10.1016/j.jmb.2012.08.002
  • Treiber Daniel K, Shah Neil P. Ins and outs of kinase DFG motifs. Chem Biol. 2013;20(6):745–746. doi: 10.1016/j.chembiol.2013.06.001
  • Wu P, Nielsen TE, Clausen MH. FDA-approved small-molecule kinase inhibitors. Trends Pharmacol Sci. 2015;36(7):422–439. doi: 10.1016/j.tips.2015.04.005
  • Choi HS, Rucker PV, Wang Z, et al. (R)-2-phenylpyrrolidine substituted imidazopyridazines: a New class of potent and selective pan-TRK inhibitors. ACS Med Chem Lett. 2015;6(5):562–567. doi: 10.1021/acsmedchemlett.5b00050
  • Cocco E, Lee JE, Kannan S, et al. TRK xDFG Mutations trigger a sensitivity switch from type I to II kinase inhibitors. Cancer Discov. 2021;11(1):126–141. doi: 10.1158/2159-8290.CD-20-0571
  • Murray BW, Rogers E, Zhai D, et al. Molecular characteristics of repotrectinib that enable potent inhibition of TRK fusion proteins and resistant mutations. Mol Cancer Ther. 2021;20(12):2446–2456. doi: 10.1158/1535-7163.MCT-21-0632
  • Drilon A, Zhai D, Deng W, et al. Abstract 442: repotrectinib, a next generation TRK inhibitor, overcomes TRK resistance mutations including solvent front, gatekeeper and compound mutations. Cancer Res. 2019;79(13_Supplement):442–42. doi: 10.1158/1538-7445.AM2019-442
  • Bailey JJ, Schirrmacher R, Farrell K, et al. Tropomyosin receptor kinase inhibitors: an updated patent review for 2010-2016 – part I. Expert Opin Ther Patents. 2017;27(6):733–751. doi: 10.1080/13543776.2017.1297796
  • Bailey JJ, Schirrmacher R, Farrell K, et al. Tropomyosin receptor kinase inhibitors: an updated patent review for 2010-2016 – part II. Expert Opin Ther Patents. 2017;27(7):831–849. doi: 10.1080/13543776.2017.1297797
  • Bailey JJ, Jaworski C, Tung D, et al. Tropomyosin receptor kinase inhibitors: an updated patent review for 2016–2019. Expert Opin Ther Patents. 2020;30(5):325–339. doi: 10.1080/13543776.2020.1737011
  • Iliev P, Jaworski C, Wängler C, et al. Type II & III inhibitors of Tropomyosin receptor kinase (Trk): a 2020-2022 patent update. Expert Opin Ther Patents. 2023.
  • Xu X, Chen J, Wang G, et al. Multi-target anti-tumor compound, preparation method therefor and use thereof. WO2021197467. 2021.
  • Liu J, Plewe MB, Wang J, et al. Tropomyosin receptor kinase (Trk) degradation compounds and methods of use. WO2020038415. 2020.
  • Chen L, Chen Y, Zhang C, et al. Discovery of first-in-class potent and selective Tropomyosin receptor kinase degraders. J Med Chem. 2020;63(23):14562–14575. doi: 10.1021/acs.jmedchem.0c01342
  • Ding K, Chan S, Zhang Z, et al. Indazole compound, pharmaceutical composition of same, and applications thereof. WO2021088859. 2021.
  • Duan Y, Wang J, Zhu S, et al. Design, synthesis, and structure–activity relationships (SAR) of 3-vinylindazole derivatives as new selective tropomyosin receptor kinases (Trk) inhibitors. Eur J Med Chem. 2020;203:112552. doi: 10.1016/j.ejmech.2020.112552
  • Shen Y, Zhu B, Wan Y Compound used as NTRK inhibitor and application thereof. WO2022095909. 2022.
  • Fu B, Li Y, Ren W, et al. Tyrosine kinase inhibitors, compositions and methods there of. WO2020114499. 2020.
  • Attwa MW, Kadi AA, Darwish HW. Metabolic stability Assessment of larotrectinib using liquid chromatography tandem Mass spectrometry. Drug Design Develop Therapy. 2020;14:111–119. doi: 10.2147/DDDT.S235934
  • Fu B, Chen L, Ke Y, et al. Salt form, crystal form, pharmaceutical composition and use of tyrosine kinase inhibitor. WO2021249450. 2021.
  • Li J, Niu C, Liang A, et al. Compound used as kinase inhibitor and application thereof. WO2020224626. 2020.
  • Li J, Liang A, Niu C, et al. Compound used as kinase inhibitor and use thereof. WO2022095910. 2022.
  • Pal K, Deb P, Prakash H, et al. Method for preparing tyrosine receptor kinase inhibitors. WO2021211882. 2021.
  • 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. doi: 10.1158/1538-7445.AM2019-2198
  • Pal K, Bhat A, Birnbaum J, et al. Topical pharmaceutical compositions and methods. WO2022144758. 2022.
  • Davies A, Ionnidis S, Lamb M, et al.; 9-(pyrazol-3-yl)-9H-purine-2-amine and 3-(pyrazol-3-yl)-3H-imidazo[4,5-b]pyridin-5-amine derivatives and their use for the treatment of cancer. WO2008135785. 2008.
  • Robas N, Stevenson CR, Prothero EAG, et al. Topical pharmaceutical compositions comprising imidazo[1,2-b]pyridazine compounds. WO2021148805. 2021.
  • Jiang L, Feng Z, Jin X, et al. Preparation and application of heteroaromatic iminazole compound. WO2020114465. 2020.
  • Jiang L, Feng Z, Lu X, et al. Preparation and uses of protein receptor kinase inhibitor. WO202078360. 2020.
  • Mi G, Zhang Y, Jiang C, et al. Fused aza-heterocyclic amide compound and use thereof. WO2021228248. 2021.
  • Ryu H-C, Kim J-S, Lim J-W, et al. Compound for inhibiting mutagenic Trk fusion protein, and pharmaceutical use and manufacturing method thereof. WO2021187878. 2021.
  • Huang G, Li B. Radioactive iodine-labelled larotrectinib compound, preparation method therefor and use thereof. WO2020119206. 2020.
  • Feng J, Dong J, Wang T-L Tricyclic compound, preparation metho therefor, and intermediate and use thereof. WO2021027503. 2021.
  • Dong J, Feng J, Wang T-L Heterocyclic compound and application thereof as Trk kinase inhibitor. WO2021042890. 2021.
  • Liu B Macrocyclic tyrosine kinase inhibitor and uses thereof. WO2020094112. 2020.
  • Zhang Y, Gao Y, Zhao D, et al. Diaryl macrocyclic compound as protein kinase modulator. WO2019210835. 2019.
  • Yang A, Huang H, Chen T, et al. Fluorine-containing heterocyclic derivatives with macrocyclic structure and use thereof. WO2021115401. 2021.
  • Li Z, Zhang X, Zhang D, et al. Application of fluorine-containing heterocyclic derivative having macrocyclic structure. WO2022033575. 2022.
  • Huang H, Liu W, Zhang S, et al. Solid form of fluorine-containing macrocyclic structure compound, preparation method, and application. WO2022218276. 2022.
  • Wang J, Zhao S, Zeng S, et al. Compound having macrocyclic structure and use thereof. WO2021244609. 2021.
  • Cui JJ, Rogers EW, Zhai D, et al. Macrocycles for treating disease. WO2020257189. 2020.
  • Cui JJ, Rogers EW, Ung J, et al. Macrocycles for use in treating disease. WO2020257165. 2020.
  • Rogers EW, Ung J, Zhang H, et al. Macrocyclic kinase inhibitors and their use. WO2019126122. 2019.
  • Cui JJ, Li Y, Rogers EW, et al. Diaryl macrocycles as modulators of protein kinases. WO2015112806, 2015.
  • Wang J, Zhang Y, Sun J, et al. Pyrazolopyrimidine derivative as selective Trk inhibitor. WO2020063965. 2020.
  • Liu Z, Yu P, Dong L, et al. Discovery of the next-generation pan-TRK kinase inhibitors for the treatment of cancer. J Med Chem. 2021;64(14):10286–10296. doi: 10.1021/acs.jmedchem.1c00712
  • Wang J, Sun J, Yang G, et al. Crystal of carcinogenic fused kinase inhibitor and applications thereof. WO2021037156. 2021.
  • Wang J, Sun J, Zhu W, et al. Pyrazolopyrimidine derivative and use thereof. WO2019165967. 2019.
  • Wu Y, Zhou W, Gong Y, et al.; Tropomyosin receptor kinase inhibitor, preparation method therefor and use thereof. US 11,597,729. 2019.
  • Kong NX, Zhou C, Zheng Z Heterocyclic compound as Trk inhibitor. WO2020001415. 2020.
  • Kong NX, Zhou C, Zheng Z Heterocyclic compound which acts as Trk inhibitor. WO2019157879. 2019.
  • Wu W-L, Yang Z, Lee F, et al. Macrocyclic compounds as kinases inhibitors and uses thereof. WO2021206955. 2021.
  • Wu W-L, Yang Z, Lee F, et al. Macrocyclic compounds as Trk kinase inhibitors and uses thereof. WO2019094143. 2019.
  • Lee FYF, Wu W-L, Yang Z, et al. Abstract 1286: AGX87 - an IND-stage potent and selective next-generation NTRK/ROS1 inhibitor of WT and clinical resistant mutants with superiority over tyrosine kinase inhibitors currently approved or in development. Cancer Res. 2021;81(13_Supplement):1286–86. doi: 10.1158/1538-7445.AM2021-1286
  • Liu G, Wang G, Sha H, et al.; Macro heterocyclic compound and medical use thereof. WO2022262671. 2022.
  • Inoue T, Kaya T, Kikuchi S, et al. Indole compound and pharmaceutical use thereof. WO2011065402A1. 2011.
  • Bagley SW, Casimiro-Garcia A, Cheng Z, et al. Benzimidazole derivatives. WO2021124155. 2021.
  • Bagley SW, Casimiro-Garcia A, Davoren JE, et al. Benzimidazole derivatives and their use as inhibitors of ITK for the treatment of skin disease. WO2022130171. 2022.
  • Bagley SW, Casimiro-Garcia A, Davoren JE, et al. Pyrido[2,3-d]imidazole derivatives and their use as inhibitors of ITK for the treatment of skin disease. WO2022130175. 2022.
  • Jain VK Crenolanib for treating Trk kinase associated proliferative disorders. WO2022060421. 2022.
  • Kapoor TM, Cupido T, Pisa R 2,4-diaminopyrimidine bicycles for treating cancer. WO2020118183. 2020.
  • Tang X, Horan JC, Mente SR, et al. Heteroaromatic macrocyclic ether chemotherapeutic agents. WO2021226208. 2021.
  • Drilon A, Horan JC, Tangpeerachaikul A. NVL-520 is a selective, TRK-Sparing, and brain-penetrant inhibitor of ROS1 fusions and secondary resistance mutations. Cancer Discov. 2023;13(3):598–615. doi: 10.1158/2159-8290.CD-22-0968
  • Liu D, Flory J, Lin A, et al. Characterization of on-target adverse events caused by TRK inhibitor therapy. Ann Oncol. 2020;31(9):1207–1215. doi: 10.1016/j.annonc.2020.05.006
  • Harada G, Choudhury NJ, Schram AM, et al. Mechanisms of acquired resistance to TRK inhibitors. J Clin Oncol. 2022;40(16_suppl):3104–04. doi: 10.1200/JCO.2022.40.16_suppl.3104
  • Cocco E, Schram AM, Kulick A, et al. Resistance to TRK inhibition mediated by convergent MAPK pathway activation. Nature Med. 2019;25(9):1422–1427. doi: 10.1038/s41591-019-0542-z
  • Xia H, Xue X, Ding H, et al. Evidence of NTRK1 fusion as resistance mechanism to EGFR TKI in EGFR+ NSCLC: results from a large-scale survey of NTRK1 fusions in Chinese patients with lung cancer. Clin Lung Cancer. 2020;21(3):247–254. doi: 10.1016/j.cllc.2019.09.004
  • Hechtman JF. NTRK insights: best practices for pathologists. Mod Pathol. 2022;35(3):298–305. doi: 10.1038/s41379-021-00913-8
  • Marchetti A, Ferro B, Pasciuto MP, et al. NTRK gene fusions in solid tumors: agnostic relevance, prevalence and diagnostic strategies. Pathologica. 2022;114(3):199–216. doi: 10.32074/1591-951X-787
  • Gao J, Aksoy BA, Dogrusoz U, et al. Integrative analysis of complex cancer genomics and clinical profiles using the cBioportal. Sci Signaling. 2013;6(269):l1. doi: 10.1126/scisignal.2004088
  • Kyker-Snowman K, Hughes RM, Yankaskas CL, et al. TrkA overexpression in non-tumorigenic human breast cell lines confers oncogenic and metastatic properties. Breast Cancer Res Treat. 2020;179(3):631–642. doi: 10.1007/s10549-019-05506-3
  • Bailey JJ, Kaiser L, Lindner S, et al. First-in-human brain imaging of [18F]TRACK, a PET tracer for Tropomyosin receptor kinases. ACS Chem Neurosci. 2019;10(6):2697–2702. doi: 10.1021/acschemneuro.9b00144

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.