BTK Inhibitor

Pirtobrutinib

BTK Inhibitor

Estupiñán HY, et al1; Mato AR, et al2; Brandhuber B, et al3; Alsadhan A, et al4; Gomez EB, et al5; Gomez EB, et al6

Target
Bruton's tyrosine kinase (BTK) is critical for the propagation of B-cell receptor signaling and is upregulated in many B-cell malignancies as compared with normal B-cells. BTK inhibition, both in vitro and in vivo, decreases proliferation and survival signals.7
Molecule
Pirtobrutinib is an investigational, oral, highly selective (in preclinical studies, over 300-fold more selective for BTK vs 98% of 370 non-BTK-kinases), non-covalent (reversible) BTK inhibitor.2,3 It possesses nanomolar potency independent of BTK C481 status in enzyme and cell-based assays.2,3,6 Pirtobrutinib has been shown in preclinical studies to reversibly bind BTK, have high target coverage regardless of BTK turnover rate, preserve activity in the presence of the C481 acquired resistance mutations, and predominantly avoid off-target kinases.2
Clinical Development
Pirtobrutinib is being investigated in clinical trials in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma, mantle cell lymphoma, and non-Hodgkin’s lymphoma.

References

  1. Estupiñán HY, et al. Front Cell Dev Biol. 2021;9:630942.
  2. Mato AR, et al. Lancet. 2021;397(10277):892-901.
  3. Brandhuber B, et al. Clin Lymphoma Myeloma Leuk. 2018;18:S216.
  4. Alsadhan A, et al. Clin Cancer Res. 2020;26(12):2800-2809.
  5. Gomez EB, et al. Blood. 2023;142(1):62-72.
  6. Gomez EB, et al. Blood. 2019;134(suppl 1):4644.
  7. Woyach JA, et al. J Clin Oncol. 2017;35(13):1437-1443.
Pirtobrutinib Mechanism of Action
Clinical Development
Pirtobrutinib is being investigated in clinical trials in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma, mantle cell lymphoma, and non-Hodgkin’s lymphoma.

References

  1. Estupiñán HY, et al. Front Cell Dev Biol. 2021;9:630942.
  2. Mato AR, et al. Lancet. 2021;397(10277):892-901.
  3. Brandhuber B, et al. Clin Lymphoma Myeloma Leuk. 2018;18:S216.
  4. Alsadhan A, et al. Clin Cancer Res. 2020;26(12):2800-2809.
  5. Gomez EB, et al. Blood. 2023;142(1):62-72.
  6. Gomez EB, et al. Blood. 2019;134(suppl 1):4644.
  7. Woyach JA, et al. J Clin Oncol. 2017;35(13):1437-1443.

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The safety and efficacy of the agents under investigation have not been established. There is no guarantee that the agents will receive regulatory approval and become commercially available for the uses being investigated.

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