2. Protein Tyrosine Kinase/RTK Neuronal Signaling
  3. RET VEGFR Trk Receptor c-Fms
  4. NPA101.3

NPA101.3 is an orally active RET receptor tyrosine kinase and VEGFR2 inhibitor (RET IC50 = 0.001 μM, RETV804M 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.

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NPA101.3

NPA101.3 Chemical Structure

CAS No. : 1839155-15-5

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NPA101.3 Related Antibodies

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TrkA TrkB TrkC Trk

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Description

NPA101.3 is an orally active RET receptor tyrosine kinase and VEGFR2 inhibitor (RET IC50 = 0.001 μM, RETV804M 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].

IC50 & Target[1]

TrkA

32 nM (IC50)

VEGFR2

0.003 μM (IC50)

Ret

0.001 μM (IC50)

RETV804M

0.008 μM (IC50)

CSF1R

46 nM (IC50)

Cellular Effect
Cell Line Type Value Description References
8505C IC50
100 nM
Compound: NPA101.3
Cytotoxicity against RET deficient human 8505C cells supplemented with fresh medium containing compound for every 2 to 3 days measured during compound dosing
Cytotoxicity against RET deficient human 8505C cells supplemented with fresh medium containing compound for every 2 to 3 days measured during compound dosing
[PMID: 32298114]
In Vitro

NPA101.3 (0.632 nM-0.2 mM; 60 min) potently inhibits purified RET (IC50 = 0.001 μM), RETV804M (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 (ΔTm = 16 °C) and RETV804M 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 RETC634R, RETM918T, RETV804L, RETV804M, and RETA883F oncoproteins in RAT1 cells, with near-complete inhibition achieved at 3 nM for RETC634R 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 Related Antibodies

Western Blot Analysis[1]

Cell Line: NIH3T3 cells expressing rearranged RET oncoproteins (CCDC6-RET, NCOA4-RET, FGFR1OP-RET)
Concentration: 1 nM-100 nM
Incubation Time: 2 h
Result: Inhibited phosphorylation of CCDC6-RET, NCOA4-RET, and FGFR1OP-RET at 1 nM, with further reduction at 10 nM.

Western Blot Analysis[1]

Cell Line: transiently VEGFR2-transfected HEK293 cells
Concentration: 0.1 nM-100 nM
Incubation Time: 2 h
Result: Reduced ligand-induced VEGFR2 autophosphorylation at 1 nM, with virtually total inhibition at 10 nM.

Cell Proliferation Assay[1]

Cell Line: RET-transformed Ba/F3 pro-B cells (Ba/F3 RET/C634R, Ba/F3 RET/M918T, Ba/F3 NCOA4-RET), parental Ba/F3 cells
Concentration: 0.2 nM-100 nM
Incubation Time: up to 4 days
Result: Inhibited proliferation of Ba/F3 RET/C634R with an IC50 of 1.7 nM.
Inhibited proliferation of Ba/F3 RET/M918T with an IC50 of 1.6 nM.
Inhibited proliferation of Ba/F3 NCOA4-RET with an IC50 of 3.1 nM.
Showed no inhibition of IL-3-driven parental Ba/F3 cell proliferation at tested concentrations.
In Vivo

NPA101.3 (1-10 mg/kg/day; p.o.; daily) completely prevents RETC634Y-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 HRASG12V-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 RETC634Y-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.

Animal Model: BALB/c nu/nu (6-week-old female)[1]
Dosage: 1.0 mg/kg/day; 3.0 mg/kg/day; 10.0 mg/kg/day
Administration: p.o.; daily
Result: Completely prevented tumor formation at 10.0 mg/kg/day.
Significantly reduced the rate of RET-driven tumor growth at 1.0 mg/kg/day and 3.0 mg/kg/day, with statistically significant differences (P ≤ 0.05, P ≤ 0.01, P ≤ 0.001) compared to vehicle controls.
Strongly inhibited RET phosphorylation and signaling in tumors at 1.0 mg/kg/day.\nWeakened but did not abrogate tumor formation at 10.0 mg/kg/day, with a statistically significant difference (P ≤ 0.05) compared to vehicle controls.
Did not significantly reduce RAS-driven tumor growth at 1.0 mg/kg/day and 3.0 mg/kg/day.
Detected VEGFR2 inhibition in RAS-driven tumors, but no effect on RAS signaling (MAPK phosphorylation) was observed.
Animal Model: BALB/c nu/nu (6-week-old female)[1]
Dosage: 0.3 mg/kg/day; 1.0 mg/kg/day; 3.0 mg/kg/day
Administration: p.o.; daily; 2 days
Result: Strongly inhibited RET autophosphorylation and signaling, as well as VEGFR2 phosphorylation in tumors at 3.0 mg/kg/day.
Molecular Weight

528.62

Formula

C29H28N4O4S
CAS No.
SMILES

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
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Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
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NPA101.3 Related Classifications

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Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

NPA101.31839155-15-5RETVEGFRTrk Receptorc-FmsVascular endothelial growth factor receptorTropomyosin related kinase receptor CSF-1 receptorcolony stimulating factor 1 receptorCSF-1RCSF1RVEGFR2RAT1 cellsRET-driven cancersHEK293 cellsNIH3T3 cellsTT human cancer cellsRET receptor tyrosine kinaseHRAS/G12V-transformed cellsRET oncoproteinsRET/C634Y-transformed cellsInhibitorinhibitorinhibit

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