pralsetinib   Click here for help

GtoPdb Ligand ID: 10033

Synonyms: BLU-667 | BLU667 | Gavreto®
Approved drug
pralsetinib is an approved drug (FDA (2020), EMA (2021))
Compound class: Synthetic organic
Comment: Pralsetinib (BLU-667) is a second-generation selective RET kinase inhibitor that is being developed by Blueprint Medicines [2]. It is Compound 130 in patent US20170121312A1 and our structure was drawn from the image therein [1]. Selective RET inhibitors have oncology potential for the treatment of solid tumours with oncogenic RET alterations (e.g. constitutively activating RET point mutations and RET gene rearrangements). They are expected to offer more effective anti-tumour efficacy in RET-driven tumours than the currently available multi-kinase inhibitors (such as cabozantinib and vandetanib) that have limited anti-RET activity, and which have exhibited poor therapeutic responses in this defined patient group.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 9
Hydrogen bond donors 3
Rotatable bonds 9
Topological polar surface area 135.01
Molecular weight 533.27
XLogP 3.29
No. Lipinski's rules broken 0
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Canonical SMILES COC1(CCC(CC1)c1nc(C)cc(n1)Nc1n[nH]c(c1)C)C(=O)NC(c1ccc(nc1)n1ncc(c1)F)C
Isomeric SMILES CO[C@@]1(CC[C@@H](CC1)c1nc(C)cc(n1)Nc1n[nH]c(c1)C)C(=O)N[C@H](c1ccc(nc1)n1ncc(c1)F)C
InChI InChI=1S/C27H32FN9O2/c1-16-11-22(33-23-12-17(2)35-36-23)34-25(31-16)19-7-9-27(39-4,10-8-19)26(38)32-18(3)20-5-6-24(29-13-20)37-15-21(28)14-30-37/h5-6,11-15,18-19H,7-10H2,1-4H3,(H,32,38)(H2,31,33,34,35,36)/t18-,19-,27+/m0/s1
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Summary of Clinical Use Click here for help
Pralsetinib (BLU-667) has advanced to clinical evaluation as a treatment for RET-altered solid tumours. Click here to link to's full list of BLU-667 studies, including the Phase 3 study (AcceleRET) in patients with RET fusion-positive metastatic non-small cell lung cancer (NSCLC). Based on positive outcomes identified by independent review of top-line data from the Phase 1/2 ARROW clinical trial (NCT03037385), Blueprint Medicines submitted a New Drug Application (NDA) to the FDA in January 2020, for pralsetinib to be considered for regulatory approval for RET fusion-positive NSCLC. A second NDA for pralsetinib for the treatment of patients with medullary thyroid cancer (who have received previous treatment with an approved multi-kinase inhibitor) followed later in 2020. In September 2020, the first FDA full approval was granted for patients with RET-mutant NSCLCs, and approval for use in certain RET-mutant medullary thyroid cancers and RET fusion-positive thyroid cancers followed in December 2020.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT03037385 Phase 1/2 Study of the Highly-selective RET Inhibitor, Pralsetinib (BLU-667), in Patients With Thyroid Cancer, Non-Small Cell Lung Cancer, and Other Advanced Solid Tumors Phase 1/Phase 2 Interventional Blueprint Medicines Corporation