Uses
GW2974 is a potent dual inhibitor of EGFR and HER2 with IC50 value of 0.007 μM and 0.016 μM, respectively. GW2974 demonstrates in vitro inhibition of the EGFR and HER2 and inhibits the growth of tumor cell. GW2974 can be used for glioblastoma multiforme (GBM) disease research[1][2].
Definition
ChEBI: N6,N6-dimethyl-N4-[1-(phenylmethyl)-5-indazolyl]pyrido[3,4-d]pyrimidine-4,6-diamine is a pyridopyrimidine.
Biological Activity
Potent and selective dual inhibitor of EGFR (IC50 = 0.016 mM) and ErbB-2 receptor tyrosine kinase.
in vivo
GW2974 (30 mg/kg, 100 mg/kg for Oral gavage, once a day) inhibits GBM growth, invasion, and angiogenesis in dose of 30 mg/kg but abrogated the inhibitory effect of low-dose GW2974 on tumor invasion in dose of 100 mg/kg in GBM xenograft mice model[1].
GW2974 (10 mg/kg, 30 mg/kg, Oral gavage, twice a day) inhibits the growth of tumor in CD-1 nude mice (HN5) and C.B-17 SCID mice (BT474) models in a dosed dependent manner[2].
| Animal Model: | GBM xenograft mice model[1] |
| Dosage: | 30 mg/kg, 100 mg/kg |
| Administration: | Oral gavage (p.o.) |
| Result: | Decelerated tumor growth at dose of 30 mg/kg and 100 mg/kg.
Inhibited the invasion to peritumor areas of tumors in 30 mg/kg group but augmented tumor invasion in 100 mg/kg group of brain tissues.
Inhibited angiogenesis in doses of 30 mg/kg and 100 mg/kg.
|
| Animal Model: | CD-1 nude mice (HN5), C.B-17 SCID mice (BT474)[2] |
| Dosage: | 10 mg/kg, 30 mg/kg |
| Administration: | Oral gavage (p.o.) |
| Result: | Inhibited tumor growth in the HN5 model by treatment dose with 30 mg/kg.
Inhibited tumor growth in the HN5 model about 95% inhibition and BT474 model about 50% inhibition by treatment dose with 10 mg/kg.
|
IC 50
EGFR
L858R/T790M: 0.007 μM (IC
50); HER2: 0.016 μM (IC
50)
References
[1] Wang L, et al. Differential effects of low- and high-dose GW2974, a dual epidermal growth factor receptor and HER2 kinase inhibitor, on glioblastoma multiforme invasion. J Neurosci Res. 2013 Jan;91(1):128-37. DOI:
10.1002/jnr.23140[2] Rusnak DW, et al. The characterization of novel, dual ErbB-2/EGFR, tyrosine kinase inhibitors: potential therapy for cancer. Cancer Res. 2001 Oct 1;61(19):7196-20. PMID:11585755
