APS03118

APS03118 is an orally active, potent and selective rearranged during transfection (RET) inhibitor. APS03118 broadly inhibits RET fusions and mutations (including G810, V804, L730, and Y806 variants), with IC50 values predominantly below 1 nM (0.095 nM for WT; ranging from 0.00438 to 5.72 nM for mutants), and demonstrates marked superiority against RET G810 mutations. APS03118 inhibits the entire RET signaling pathway (including RET, Shc, and ERK1/2), with >20-fold selectivity over most off-target kinases (except FLT3 and YES) . APS03118 induces complete tumor regression in KIF5B-RET and CCDC6-RET V804 M patient derived xenografts (PDXs) and significantly prolongs survival in an intracranial CCDC6-RET metastasis mice model. APS03118 can be used for selective RET inhibitor (SRI) -resistant, RET-driven cancer research[1].

Product Specifications

CAS Number

[2598870-24-5]

UNSPSC

12352005

Target

ERK; RET

Related Pathways

MAPK/ERK Pathway; Protein Tyrosine Kinase/RTK; Stem Cell/Wnt

Applications

Cancer-Kinase/protease

Field of Research

Cancer

Smiles

CCOC1=CN2NC3=NN=CC3=C2C(C4=CC=C(N5CC6N(C(C6)C5)CC7=CN=C(C=C7)OC)N=C4)=C1

Molecular Formula

C27H28N8O2

Molecular Weight

496.56

References & Citations

[1]Zhong J, et al. Discovery of APS03118, a Potent and Selective Next-Generation RET Inhibitor with a Novel Kinase Hinge Scaffold. J Med Chem. 2025 Sep 25;68 (18) :19536-19553.