In the co-crystal structure of selpercatinib-RET
kinase, the pyrazolopyridine occupies the
adenosine pocket, forming a direct hydrogen bond
between N1 and amide NH of Ala807 and an indirect
hydrogen bond between C6 ether oxygen and amide
NH of Gly810 via a bound water molecule. In addition,
one piperazine nitrogen also interact with one water
molecule (Figs. 3, 4).
Selpercatinib is a highly selective, potent RET inhibitor, an oral drug used to treat cancers in people whose tumours have been altered (mutated or fused) in specific genes (RET stands for "rearrangement during transfection").
Class: receptor tyrosine kinase;
Treatment: RET-altered lung/thyroid cancers;
Other name: ARRY-192, LOXO-292;
Oral bioavailability = 73%;
Elimination half-life = 32 h;
Protein binding = 97%
Selpercatinib can cause serious side effects including liver toxicity, high blood pressure, heart rhythm changes due to prolongation of heart electrical activity (QT prolongation), bleeding, allergic reactions, impaired wound healing and harm to an unborn baby.
Selpercatinib may cause harm to a developing fetus or a newborn baby.
The recommended selpercatinib dose based on body weight is:
(1) Less than 50 kg: 120 mg orally twice daily
(2) 50 kg or greater: 160 mg orally twice daily
