selitrectinib   Click here for help

GtoPdb Ligand ID: 10314

Synonyms: BAY 2731954 | BAY-2731954 | example 28 [WO2017075107A1] | LOXO-195 | LOXO195
Compound class: Synthetic organic
Comment: Selitrectinib (LOXO-195) is an oral tyrosine kinase inhibitor that is being developed by Loxo Oncology for antineoplastic potential [1]. Mechanistically it is a selective neurotrophic receptor tyrosine kinase (NTRK) inhibitor that is designed to overcome acquired resistance caused by kinase domain mutations in NTRK fusion-positive tumours.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 6
Hydrogen bond donors 1
Rotatable bonds 0
Topological polar surface area 75.42
Molecular weight 380.18
XLogP 3.18
No. Lipinski's rules broken 0
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Canonical SMILES CC1CCc2ncc(cc2C2CCCN2c2nc3c(C(=O)N1)cnn3cc2)F
Isomeric SMILES C[C@@H]1CCc2ncc(cc2[C@H]2CCCN2c2nc3c(C(=O)N1)cnn3cc2)F
InChI InChI=1S/C20H21FN6O/c1-12-4-5-16-14(9-13(21)10-22-16)17-3-2-7-26(17)18-6-8-27-19(25-18)15(11-23-27)20(28)24-12/h6,8-12,17H,2-5,7H2,1H3,(H,24,28)/t12-,17-/m1/s1
Bioactivity Comments
LOXO-195 inhibits mutant NTRKA, B and C with low nanomolar IC50s [2] [nM IC50 values in brackets:-TRKAV573M (<5.0), TRKAF589L (3.3), TRKAG595R (2.0), TRKAG667C (9.8), TRKAG667S (2.3), TRKBG623R (1.9), TRKCG623R (2.8), TRKCF617L (<5.0)].
Selectivity at catalytic receptors
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
neurotrophic receptor tyrosine kinase 1 Hs Inhibitor Inhibition >9.3 pIC50 - 2
pIC50 >9.3 (IC50 <5x10-10 M) [2]
neurotrophic receptor tyrosine kinase 3 Hs Inhibitor Inhibition >8.6 pIC50 - 2
pIC50 >8.6 (IC50 <2.5x10-9 M) [2]
neurotrophic receptor tyrosine kinase 2 Hs Inhibitor Inhibition 8.5 pIC50 - 2
pIC50 8.5 (IC50 3.2x10-9 M) [2]