Synonyms: KPT-9274 | KPT9274 | PAK4-IN-1
Compound class:
Synthetic organic
Comment: KPT-9274 is a small molecule that has reported inhibitory activity against PAK4 and NAMPT [3,6]. It is being developed by Karyopharm Therapeutics for anti-cancer efficacy in solid tumours [2,5] and in B cell malignancies [7]. KPT-9274 is suggested to act as an allosteric modulator of PAK4 that does not interfere with the enzyme's kinase activity (in contrast to the type 1 ATP-competitive PAK kinase inhibitor PF-3758309). It produces dose-dependent antitumour effects in solid and haematologic cell lines at low nanomolar concentrations [1]. KPT-9274 is claimed as example 728 in patent WO2015003166A1 [4].
The chemical structure of KPT-9274 is identical to that which was submitted to the WHO for the INN padnarsertib (proposed INN list 126, Jan 2022). |
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Bioactivity Comments |
KPT-9274 inhibits recombimant human NAMPT with an IC50 of 120 nM in a cell-free assay [3]. KPT-9274 inhibits proliferation of MS751 cervical carcinoma and Z138 B cell acute lymphoblastic leukemia cell lines with IC50 values <100 nM in vitro, and induces shrinkage of Molt-4 (T cell acute lymphoblastic leukemia) xenografts in SCID mice [4]. |