2,047
Views
7
CrossRef citations to date
0
Altmetric
Review

Inhibitors of immuno-oncology target HPK1 – a patent review (2016 to 2020)

&
Pages 893-910 | Received 05 Mar 2021, Accepted 28 Apr 2021, Published online: 20 May 2021

References

  • Kim R, Emi M, Tanabe K. Cancer immunoediting from immune surveillance to immune escape. Immunology. 2007;121(1):1–14.
  • Khalil DN, Smith EL, Brentjens RJ, et al. The future of cancer treatment: immunomodulation, CARs and combination immunotherapy. Nature Reviews Clinical Oncology. 2016;13(5):273–290.
  • Chen DS, Mellman I. Oncology meets immunology: the cancer-immunity cycle. Immunity. 2013;39(1):1–10.
  • Lee HT, Lee SH, Heo YS. Molecular interactions of antibody drugs targeting PD-1, PD-L1, and CTLA-4 in immuno-oncology. Molecules. 2019;24(6): 1190–120.
  • Sharma P, Hu-Lieskovan S, Wargo JA, et al. Primary, adaptive, and acquired resistance to cancer immunotherapy. Cell. 2017;168(4):707–723.
  • Dhanak D, Edwards JP, Nguyen A, et al. Small-molecule targets in immuno-oncology. Cell Chemical Biology; 2017; 24 (9):1148-1160.Toogood, PL. Small molecule immuno-oncology therapeutic agents. Bioorg Med Chem Lett. 2018;28(3):319–329.
  • Sawasdikosol S, Zha R, Yang B, et al. HPK1 as a novel target for cancer immunotherapy. Immunol Res. 2012;54(1–3):262–265.
  • Hu MC, Qiu WR, Wang X, et al. Human HPK1, a novel human hematopoietic progenitor kinase that activates the JNK/SAPK kinase cascade. Genes Devel. 1996;10(18):2251–2264.
  • Chuang H-C, Wang X, Tan T-H, et al. MAP4K Family Kinases in Immunity and Inflammation. Adv Immunol. 2016;129: 277–314.
  • Kiefer F, Tibbles LA, Anafi M, et al. HPK1, a hematopoietic protein kinase activating the SAPK/JNK pathway. EMBO J. 1996;15(24):7013–7025. Human HPK1, a novel human hematopoietic progenitor kinase that activates the JNK/SAPK kinase cascade. Genes Devel. 1996; 10:2251–2264KieferF, Tibbles LA, Anafi M, et al.
  • Brenner D, Brechmann M, Röhling S, et al. Phosphorylation of CARMA1 by HPK1 is critical for NF- B activation in T cells. Proc Nat Acad Sci USA. 2009;106(34):14508–14513.
  • Ling P, Meyer CF, Redmond LP, et al. Involvement of hematopoietic progenitor kinase 1 in t cell receptor signaling. J Bio Chem. 2001;276(22):18908–18914.
  • Sauer K, Liou J, Singh SB, et al. Hematopoietic progenitor kinase 1 associates physically and functionally with the adaptor proteins B cell linker protein and SLP-76 in lymphocytes. J Bio Chem. 2001(276):45207–45216.
  • Arnold R, Patzak IM, Neuhaus B, et al. Activation of hematopoietic progenitor kinase 1 involves relocation, autophosphorylation, and transphosphorylation by protein kinase D1. Mol Cell Biol. 2005;25(6):2364–2383.
  • Di Bartolo V, Montagne B, Salek M, et al. A novel pathway down-modulating T cell activation involves HPK-1–dependent recruitment of 14-3-3 proteins on SLP-76. J Exp Med. 2007;204(3):681–691.
  • Lasserre R, Cuche C, Blecher-Gonen R, et al. Release of serine/threonine-phosphorylated adaptors from signaling microclusters down-regulates T cell activation. J Cell Biology. 2011;195(5):839–853.
  • Alzabin S, Pyarajan S, Yee H, et al. Hematopoietic progenitor kinase 1 is a critical component of prostaglandin E2-mediated suppression of the anti-tumor immune response. Cancer Immunol. Immunotherapy. 2010;59(3):419–429.
  • Hernandez S, Qing J, Thibodeau RH, et al. The kinase activity of hematopoietic progenitor kinase 1 is essential for the regulation of t cell function. Cell Rep. 2018;25(1):80–94.
  • Wang Y, Zhang K, Georgiev P, et al. Pharmacological inhibition of hematopoietic progenitor kinase 1 positively regulates T-cell function. PLoS One. 2020;15(12):e0243145.
  • Alzabin S, Bhardwaj N, Kiefer F, et al. Hematopoietic progenitor kinase 1 is a negative regulator of dendritic cell activation. The Journal of Immunology. 2009;182(10):6187–6194.
  • Wu P, Sneeringer CJ, Pitts KE, et al. Hematopoietic progenitor kinase-1 structure in a domain-swapped dimer. Structure. 2019;27(1):125–133.
  • Johnson E, McTigue M, Gallego RA, et al. Multiple conformational states of the HPK1 kinase domain in complex with sunitinib reveal the structural changes accompanying HPK1 trans-regulation. J Biol Chem. 2019;294(23):9029–9036.
  • Lau WL, Pearce B, Malakian H, et al. Using yeast surface display to engineer a soluble and crystallizable construct of hematopoietic progenitor kinase 1 (HPK1). Acta Crystallogr F Struct Biol Commun. 2021;F77:22–28.
  • Marcotte D, Rushe M, Arduini RM, et al. Germinal-center kinase-like kinase co-crystal structure reveals a swapped activation loop and C-terminal extension. Protein Sci. 2017;26(2):152–162.
  • Sawasdikosol S, Burakoff S. The structure of HPK1 kinase domain: to boldly go where no immuno-oncology drugs have gone before. Structure. 2019;27(1):1–3.
  • WO2016/205942. HPK1 inhibitors and methods of using same
  • Davis MI, Hunt JP, Herrgard S, et al. Comprehensive analysis of kinase inhibitor selectivity. Nat Biotechnol. 2011;29(11):1046–1051.
  • Safety and Efficacy Study Of CFI-402411 in Subjects With Advanced Solid Malignancies. Available from https://clinicaltrials.gov/ct2/show/NCT04521413 accessed 2021 Feb 19
  • WO2016/090300. Methods and compositions for treating cancer using PD-1 axis antagonists and HPK1 antagonists
  • WO2018/167147. Azaindoles as inhibitors of HPK1
  • WO2020/061377. Spirocyclic 2,3-dihydro-7-azaindoles and uses there of
  • WO2018/183964. Isoquinolines as inhibitors of HPK1
  • WO2020/023551. Naphthyridine compounds and uses thereof
  • WO2020/023560. Isoquinoline compounds and uses thereof
  • WO2020/069402. Cinnoline compounds and for the treatment of HPK1-dependent disorders such as cancer
  • WO2020/072627. Isoquinoline compounds for the treatment of cancer
  • WO2020/072695. 8-Aminoisoquinoline compounds and uses thereof
  • Lacey BM, Xu Z, Chai X, et al. Development of high-throughput assays for evaluation of hematopoietic progenitor kinase 1 inhibitors. SLAS Discov. 2021;26(1):88–99.
  • WO2018/081531. Methods for human T-cell activation
  • WO2018/102366. Anilinopyrimidines as Haematopoietic progenitor kinase 1 (HPK1) inhibitors
  • Huang WS, Liu S, Dong Z, et al. Discovery of brigatinib (AP26113), a phosphine oxide-containing, potent, orally active inhibitor of anaplastic lymphoma kinase. J Med Chem. 2016;59(10):4948–4964.
  • WO2018/228923. Substituted pyrrolopyridine-derivatives as MAP4K1 modulators for the treatment of cancer diseases
  • WO2018/228920. Preparation of substituted pyrrolopyridine derivatives as anticancer agents
  • WO2018/228925. Preparation of substituted pyrrolopyridine derivatives as anticancer agents
  • WO2019/016071. Substituted pyrrolopyridine derivatives
  • WO2020/120257. Substituted pyrrolopyridine derivatives
  • WO2020/092528. Substituted 6-azabenzimidazole compounds having HPK1 inhibitory activity
  • WO2020/092621 – Substituted 6-azabenzimidazole compounds as HPK1 inhibitors
  • WO2020/237025 – Substituted exo-methylene-oxindoles which are HPK1/MAP4K1 inhibitors
  • WO2020/193511. HPK1 inhibitors
  • WO2020/193512. Bicyclic HPK1 inhibitors
  • WO2020/100027. 2,3-Dihydro-1H-pyrrolo[3,4-C]pyridine-1-one derivatives as HPK1 inhibitors for the treatment of cancer
  • WO2020/070331. Indoline compounds for use as MAP4K1 inhibitors
  • WO2020/070332. Oxindole compounds for use as MAP4K1 inhibitors
  • WO2019/238067. Pyrrolo[2,3-b]pyridines or pyrrolo[2,3-b]pyrazines as HPK1 inhibitor and the use thereof
  • WO2020/103896. Pyrrolo[2,3-b]pyridines as HPK1 inhibitor and uses thereof
  • WO2021/000925. Pyrrolo[2,3-b]pyrazines as HPK1 inhibitor and the use thereof
  • WO2019/206049. HPK1 inhibitors, preparation method and application thereof
  • Si J, Shi X, Sun S, et al. Hematopoietic Progenitor Kinase1 (HPK1) mediates T-cell Dysfunction and Is a Druggable Target for T-cell-Based Immunotherapies. Cancer Cell. 2020;38(4):551–566.
  • Toure M, Crews CM. Small-molecule PROTACS: new approaches to protein degradation. Angew Chem Int Ed Engl. 2016;55(6):1966–1973.
  • WO2020/227325. Heterobifunctional compounds as degraders of HPK1
  • WO 2019/090198. Isofuranone compounds useful as HPK1 inhibitors in the treatment of cancer and viral infections and their preparation
  • WO 2018/049152. Preparation of pyrazolopyrimidine derivatives as HPK1 modulators and their use for the treatment of cancer
  • WO 2018/049191. Pyrazolopyridone derivatives as HPK1 modulator and uses thereof for the treatment of cancer
  • WO 2018/049200. Pyrazolopyridine derivatives as HPK1 modulator and uses thereof for the treatment of cancer
  • WO 2018/049214. Pyrazolopyridine derivatives as HPK1 modulators and uses thereof for the treatment of cancer.
  • WO 2018/152220. Pyrazolopyridine compounds and uses thereof.
  • WO 2019/051199. 6-Cyano-indazole compounds as hematopoietic progenitor kinase 1 (HPK1) modulators
  • US 2019/0256500. Preparation of indazolyl pyrimidines compounds and uses thereof.
  • US 2019/0256520. Indazole compounds and uses thereof.
  • US 201900315717. Preparation of benzimidazole and indole compounds for inhibiting HPK1 activity.
  • WO 2019/164846. N-(Phenyl)-2-(phenyl) pyrimidine-4-carboxamide derivatives and related compounds as HPK1 inhibitors for treating cancer.
  • US 20200048141. Preparation of benzothiazole as HPK1 inhibitors for the treatment and prevention of cancer.
  • WO2021/026180. Solid Forms of an HPK1 inhibitor
  • Chuang H-C, Lan J-L, Chen D-Y, et al. The kinase GLK controls autoimmunity and NF-κB signaling by activating the kinase PKC-θ in T-cells. Nat Immunol. 2011;12(11):1113–1118.
  • Chuang H-C, Tsai C-Y, Hsueh C-H, et al. GLK-IKKβ signaling induces dimerization and translocation of the AhR-RORγt complex in IL-17A induction and autoimmune disease. Sci Adv. 2018;4(9):eaat5401.
  • Yang B, Wu Q, Huan X, et al. Discovery of a series of 1H-pyrrolo[2,3-b]pyridine compounds as potent TNIK inhibitors. Bioorganic Medicinal Chemistry. 2012;33:127749.
  • Parsons SJ, Parsons JT. SRC family kinases, key regulators of signal transduction. Oncogene. 2004;23(48):7906–7909.
  • You D, Hillerman S, Locke G, et al. Enhanced antitumor immunity by a novel small molecule HPK1 inhibitor. J Immunother Cancer. 2021;9(1):e001402.
  • Degnan AP, Kumi GK, Allard CW, et al. Discovery of orally active isofuranones as potent, selective inhibitors of hematopoietic progenitor kinase 1. ACS Med Chem Lett. 2021;12(3):xxx.
  • BGB-15025 alone and in combination with anti-PD-1 monoclonal antibody tislelizumab in participants with advanced solid tumors. [cited 2021 Feb 24]. Available from https://clinicaltrials.gov/ct2/show/NCT04649385
  • [cited 2020 Oct 22]. Available from: https://www.nimbustx.com/2020/10/22/nimbus-therapeutics-to-present-new-data-on-novel-hpk1-inhibitors-at-upcoming-scientific-conferences/
  • [cited 2021 Jan 11]. Available from: http://ir.blueprintmedicines.com/news-releases/news-release-details/blueprint-medicines-reports-portfolio-milestones-and-outlines
  • Chmielewski S, Kujawa M, Zimolag E, et al. Abstract 1947: development and characterization of small molecule HPK1 inhibitors. AACR. 2020;80(16):Supplement 2020.

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.