Ripretinib

Absorption

Ripretinib is absorbed in the gastrointestinal tract and Tmax is achieved in 4 hours, with steady-state concentrations reached within 14 days.

Toxicity

There is limited information in the literature regarding an overdose with ripretinib, and LD50 information is not readily available. Like other kinase inhibitors, an overdose with ripretinib likely results in hematological toxicity, skin toxicity, as well as muscle, liver, and gastrointestinal toxicity.

The Uses of Ripretinib

Ripretinib is used in the treatment of gastrointestinal stromal tumors (GISTs).

Indications

Ripretinib is indicated to treat adults diagnosed with advanced gastrointestinal stromal tumor (GIST) who have had prior therapy with at least 3 kinase inhibitors, including with imatinib.

Background

Ripretinib is a kinase inhibitor used for the treatment of advanced gastrointestinal stromal tumor (GIST) that has not adequately responded to other kinase inhibitors such as sunitinib and imatinib. Ripretinib, also known as Qinlock, is manufactured by Deciphera Pharmaceuticals and was initially approved by the FDA on May 15, 2020.
It is the first drug approved as a fourth-line therapy in the specific setting of prior treatment with a minimum of 3 other kinase inhibitors.

brand name

Qinlock

General Description

Class: receptor tyrosine kinase; Treatment: GIST; Other name: DCC-2618; Elimination half-life = 15 h; Protein binding = 98.8%

Biological Activity

Ripretinib is a highly effective inhibitor of both wild-type KIT and PDGFRA, with IC50 values around 3 nM. It also targets a wide range of KIT and PDGFRA mutants in GIST. Additionally, it inhibits various tumor-driving kinases such as PDGFRβ, TIE2, VEGFR2, and BRAF.

Pharmacokinetics

As a broad-spectrum kinase inhibitor, ripretinib inhibits various gene mutations, increasing progression-free survival in patients with advanced gastrointestinal stromal tumors (GIST). It is effective in treating mutations that are resistant to chemotherapy with other kinase inhibitors, such as imatinib.
Ripretinib has the propensity to cause cardiac dysfunction and new primary cutaneous malignancy. It is important to measure cardiac ejection fraction before and during treatment as well as to perform regular dermatological assessments.

Metabolism

Ripretinib is metabolized by the CYP3A subfamily of enzymes with contributions from CYP2D6 and CYP2E1 to its active metabolite, DP-5439.