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Tovorafenib: A novel B‑RAF inhibitor for the treatment of pediatric low‑grade glioma (Review)

  • Authors:
    • Hyma Mandapaka
    • Surya K. De
  • View Affiliations / Copyright

    Affiliations: Department of Chemistry, Wichita State University, Wichita, KS 67260, USA, Department of Chemistry, Conju‑Probe, San Diego, CA 92121, USA
    Copyright: © Mandapaka et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].
  • Article Number: 65
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    Published online on: May 20, 2026
       https://doi.org/10.3892/wasj.2026.480
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Abstract

The normal function of the RAF kinases (including BRAF and CRAF) is to relay signals from upstream activators (e.g., RAS) to the downstream effectors, MEK to ERK, thereby forming the RAF/MEK/ERK cascade (also known as the MAPK signaling pathway). This pathway regulates key cellular processes, such as proliferation, growth, differentiation and survival. In numerous types of cancer, including pediatric low‑grade gliomas, genetic alterations (mutations in BRAF, or BRAF fusions/rearrangements) lead to the constitutive activation of RAF, independent of upstream controls, resulting in uncontrolled cell proliferation and survival. Tovorafenib binds to RAF kinases (mutant or wild‑type, monomeric or dimeric) in their inactive DFG‑out state. Tovorafenib inhibits RAF kinase activity, prevents downstream MEK and ERK activation, disrupts MAPK signaling, resulting in the attenuation of inhibition of tumor cell growth; tumor regression or stabilization may thus occur. The present review discusses the efficacy of tovorafenib for the treatment of pediatric low‑grade glioma, as well as its association with RAF kinase activity and pharmacokinetics. 
View Figures

Figure 1

RAF signaling pathway. RAF, rapidly
accelerated fibrosarcoma; RTK, receptor tyrosine kinase; GRB2,
growth factor receptor-bound protein 2; SOS, son of sevenless;
PI3K, phosphatidylinositol 3-kinase; GDP, guanosine diphosphate;
GTP, guanosine triphosphate; PIP2, phosphatidylinositol
4,5-bisphosphate; PIP3, phosphatidylinositol 3,4,5-trisphosphate;
AKT, AKR mouse thymoma; ERK, extracellular signal-regulated kinase;
mTOR, mammalian target of rapamycin.

Figure 2

Synthesis of tovorafenib: Reagents and
conditions: (a) Oxalyl chloride, DMF, DME, r. t., 2 h; (b)
pyridine, CH3CN, 10˚C to r. t., 96%; (c)
NH2OH, 45˚C, 5 h, 98%; (d) Zn, AcOH, 0˚C to 30˚C, 77%;
(e) D-di-p-toluoyl tartaric acid, isopropanaol,
Na2CO3, H2O, 53˚C to r. t., 88%;
(f) EDC, HOBt, DIEA, DMF, r. t., 84%.

Figure 3

Hydrogen bonding networks of
tovorafenib with BRAF.
View References

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Copy and paste a formatted citation
Spandidos Publications style
Mandapaka H and De SK: Tovorafenib: A novel B‑RAF inhibitor for the treatment of pediatric low‑grade glioma (Review). World Acad Sci J 8: 65, 2026.
APA
Mandapaka, H., & De, S.K. (2026). Tovorafenib: A novel B‑RAF inhibitor for the treatment of pediatric low‑grade glioma (Review). World Academy of Sciences Journal, 8, 65. https://doi.org/10.3892/wasj.2026.480
MLA
Mandapaka, H., De, S. K."Tovorafenib: A novel B‑RAF inhibitor for the treatment of pediatric low‑grade glioma (Review)". World Academy of Sciences Journal 8.4 (2026): 65.
Chicago
Mandapaka, H., De, S. K."Tovorafenib: A novel B‑RAF inhibitor for the treatment of pediatric low‑grade glioma (Review)". World Academy of Sciences Journal 8, no. 4 (2026): 65. https://doi.org/10.3892/wasj.2026.480
Copy and paste a formatted citation
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Spandidos Publications style
Mandapaka H and De SK: Tovorafenib: A novel B‑RAF inhibitor for the treatment of pediatric low‑grade glioma (Review). World Acad Sci J 8: 65, 2026.
APA
Mandapaka, H., & De, S.K. (2026). Tovorafenib: A novel B‑RAF inhibitor for the treatment of pediatric low‑grade glioma (Review). World Academy of Sciences Journal, 8, 65. https://doi.org/10.3892/wasj.2026.480
MLA
Mandapaka, H., De, S. K."Tovorafenib: A novel B‑RAF inhibitor for the treatment of pediatric low‑grade glioma (Review)". World Academy of Sciences Journal 8.4 (2026): 65.
Chicago
Mandapaka, H., De, S. K."Tovorafenib: A novel B‑RAF inhibitor for the treatment of pediatric low‑grade glioma (Review)". World Academy of Sciences Journal 8, no. 4 (2026): 65. https://doi.org/10.3892/wasj.2026.480
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