2097132-94-8

Pralsetinib is a potent, selective RET inhibitor, and was optimized from a hit compound identified from a compound library that included more than 60 chemical scaffolds. However, as of 2020, detailed medicinal chemistry on the optimization process has yet to be published. Pralsetinib proved to be more potent and selective than cabozantinib or vandertanib against both wild-type and abnormal RET. The agent also showed a level of selectivity against RET relative to VEGFR2, whereas previous agents showed very little selectivity. It was approved for clinical use in 2020.

Pralsetinib is a highly potent and selective RET inhibitor designed for RET-driven cancers.

Pralsetinib is the second selective RET inhibitor approved by the FDA (following Lilly's selpercatinib) for the treatment of adult patients with metastatic RET (rearranged during transfection) fusion-positive non-small cell lung cancer (NSCLC); (2) adult and pediatric patients >=12 years of age with advanced or metastatic RET-mutant medullary thyroid cancer (MTC) who require systemic therapy; and (3) adult and pediatric patients >=12 years of age with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory.

Gavreto

[1] GAIKWAD RAJENDRA. Green One-Pot Chemo-Enzymatic Synthesis of a Key Chiral Amine Intermediate: Useful to Pralsetinib Synthesis[J]. ChemistrySelect, 2023. DOI:10.1002/slct.202204409.
[2] HUGHES* D L. Review of Synthetic Routes and Crystalline Forms of the Oncology Drugs Capmatinib, Selpercatinib, and Pralsetinib[J]. Organic Process Research & Development, 2021. DOI:10.1021/acs.oprd.1c00282.

Class: receptor tyrosine kinase; Treatment: RET-altered lung, thyroid cancers; Other name: BLU-667; Elimination half-life = 22 h; Protein binding = 97%

Pralsetinib may cause side effects: Nausea, vomiting, loss of appetite, diarrhea, constipation, extreme tiredness, dizziness, weakness, night sweats, rapid heartbeat, heartburn, shortness of breath, headache, sores in the mouth, confusion, changes in vision, fever, cough, chills, nosebleeds, pale skin, rash, itching, hives, weight changes, hair loss, back pain, muscle pain, joint pain, bone pain, unusual bruising or bleeding, blood in the urine or stool, bloody or black tarry stools, difficulty falling asleep or staying asleep, unusual vaginal bleeding, and other less common effects.

Primary target: RET

Store at 4°C

Kinase inhibitor of wild-type RET, oncogenic RET fusions, and select mutations. Pralsetinib may also inhibit other pathways including those through FLT3, JAK1-2, PDGFRB, VEGFR-2, and FGFR1. RET fusion proteins and activating point mutations can act as oncogenic drivers by promoting cell proliferation of tumor cell lines and pralsetinib inhibits this process.