Multi-targeted kinase and antifolate profile (RTK/Antifolate Profile)

This target profile represents a multi-targeted therapeutic approach combining the inhibition of several receptor tyrosine kinases (RTKs) and folate-dependent enzymes. The first component includes VEGFR1-3, PDGFR-α/β, and FGFR1-3, which are critical for angiogenesis, fibroblast proliferation, and tumor growth, as well as non-receptor kinases like Src, FLT-3, and RET that mediate intracellular signaling. The second component consists of Thymidylate Synthase (TS), Dihydrofolate Reductase (DHFR), and Glycinamide Ribonucleotide Formyltransferase (GARFT), which are essential enzymes in the folate pathway required for the synthesis of purine and pyrimidine nucleotides. This combined profile is most notably associated with the therapeutic regimen of Nintedanib (a triple angiokinase inhibitor) and Pemetrexed (a multitargeted antifolate), which has been extensively studied in the treatment of non-small cell lung cancer (NSCLC). By simultaneously targeting tumor vascularization and DNA synthesis, this profile aims to overcome resistance mechanisms and provide synergistic anti-tumor activity.

Other names

Nintedanib and Pemetrexed target profileTriple angiokinase and multitargeted antifolate profileVEGFR/PDGFR/FGFR/Src/FLT3/RET and TS/DHFR/GARFT inhibition

This profile represents a combination of two distinct therapeutic mechanisms: the inhibition of multiple receptor tyrosine kinases (VEGFR1-3, PDGFR-α/β, FGFR1-3) and non-receptor tyrosine kinases (Src, FLT-3, RET) to block angiogenesis and cell signaling, combined with the inhibition of folate-dependent enzymes (Thymidylate synthase, Dihydrofolate reductase, and Glycinamide ribonucleotide formyltransferase) to disrupt de novo nucleotide biosynthesis and DNA replication.