NPA101.3 

NPA101.3 is an orally active RET receptor tyrosine kinase and VEGFR2 inhibitor (RET IC₅₀ = 0.001 μM, RET^V804M IC₅₀ = 0.008 μM, VEGFR2 IC₅₀ = 0.003 μM). NPA101.3 inhibits purified TRKA (IC₅₀ = 32 nM) and CSF1R (IC₅₀ = 46 nM). NPA101.3 completely suppresses tumor formation in RET^/C634Y-transformed cells and also attenuates tumor formation in HRAS^/G12V-transformed cells. NPA101.3 can be used in the research of RET-driven cancers^[1].

NPA101.3 (0.632 nM-0.2 mM; 60 min) potently inhibits purified RET (IC₅₀ = 0.001 μM), RET^V804M (IC₅₀ = 0.008 μM), VEGFR2 (IC₅₀ = 0.003 μM), TRKA (IC₅₀ = 32 nM), and CSF1R (IC₅₀ = 46 nM) in a cell-free in vitro kinase assay^[1].
NPA101.3 (40 μM; 240 min) increases the thermal stability of purified wild type RET (ΔT_m = 16 °C) and RET^V804M mutant kinase domains to the same degree, confirming tight binding in a type 2 mode^[1].
NPA101.3 inhibits hERG channel conductibility with an IC₅₀ of 7.57 μM, showing minimal hERG activity relative to its RET inhibitory potency^[1].
NPA101.3 (0.1 nM-100 nM; 2 h) inhibits phosphorylation of RET^C634R, RET^M918T, RET^V804L, RET^V804M, and RET^A883F oncoproteins in RAT1 cells, with near-complete inhibition achieved at 3 nM for RET^C634R and 10 nM for the other mutants^[1].
NPA101.3 (1 nM-100 nM; 2 h) inhibits phosphorylation of rearranged CCDC6-RET, NCOA4-RET, and FGFR1OP-RET oncoproteins in NIH3T3 cells, with inhibition detectable at 1 nM^[1].
NPA101.3 (0.1 nM-100 nM; 2 h) inhibits ligand-induced VEGFR2 phosphorylation in HEK293 cells, with near-complete inhibition achieved at 10 nM^[1].
NPA101.3 inhibits RET autophosphorylation and downstream SHC/MAPK signaling in TT, MZ-CRC-1, and TPC-1 human cancer cells, and inhibits RET and SHC phosphorylation in Lc-2/ad cells, with no effect on RET-negative control cells^[1].
NPA101.3 potently inhibits proliferation of RET-positive TT, MZ-CRC-1, TPC-1, and Lc-2/ad human cancer cells (IC₅₀ = 0.67−3.6 nM) and has no effect on RET-negative human cancer cells at concentrations ≤100 nM^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

NPA101.3 (1-10 mg/kg/day; p.o.; daily) completely prevents RET^C634Y-driven tumor formation at 10.0 mg/kg/day and significantly reduces tumor growth at lower doses in BALB/c nu/nu mice^[1].
NPA101.3 (1-10 mg/kg/day; p.o.; daily) at 10.0 mg/kg/day reduces but does not eliminate HRAS^G12V-driven tumor formation in BALB/c nu/nu mice, likely via VEGFR2 inhibition^[1].
NPA101.3 (0.3-3 mg/kg/day; p.o.; daily; 2 days) at 3.0 mg/kg/day strongly inhibits RET and VEGFR2 phosphorylation and signaling in RET^C634Y-driven tumors in BALB/c nu/nu mice^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

528.62

C₂₉H₂₈N₄O₄S

1839155-15-5

O=C(CC1=CC=C(N2C=NC3=CC(C4=CC=C(S(=O)(C)=O)C=C4)=CC=C32)C=C1)NC5=NOC(C(C)(C)C)=C5

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Moccia M, et al. Bioisosteric Discovery of NPA101.3, a Second-Generation RET/VEGFR2 Inhibitor Optimized for Single-Agent Polypharmacology. J Med Chem. 2020;63(9):4506-4516.  [Content Brief]