Truqap(capivasertib)

Truqap (capivasertib) is a drug indicated for the treatment of certain cancers. It demonstrates efficacy through the inhibition of various kinases and downstream targets. Capivasertib inhibits AKT1 with an IC50 of 3.2 nM, AKT2 with an IC50 of 8.5 nM, and AKT3 with an IC50 of 7.7 nM. It also inhibits PKA with an IC50 of 6.6 nM and p70S6K with IC50s of 5.8 nM (radioactive filter binding assay) and 8.9 nM (recombinant kinase assay). Inhibition of AKT downstream targets (GSK3β, PRAS40, S6) in cancer cell lines ranged from 0.07 to 2.57 µM, and in LNCaP cells, IC50s were 0.08 and 0.36 µM. Sensitivity to capivasertib showed correlations with PIK3CA mutations (p=0.03) and PTEN mutations (p=0.02).

In terms of safety, capivasertib showed a reduction in contractility of 41% at 3.33 mg/kg in guinea pigs. It also caused a decrease in heart rate in dogs at 5 mg/kg (17% at 2h, 14% at 8h) and a peak decrease in systolic blood pressure of 20-25% and diastolic blood pressure of 28-30% at 30 and 40 mg/kg. Prolongation of QT interval and QTcR in dogs at 30 and 40 mg/kg ranged from 6-13% and 5-12%, respectively. The IC50 for hERG channel activity was 73.0 µM. The recommended dose of Truqap is 400 mg, administered with 500 mg of fulvestrant. The Marketing Authorisation Application was submitted on 20 April 2023, and the drug received approval on 16 November 2023.