NVP-BGT226

NVP-BGT226 - Names and Identifiers

Name	8-(6-methoxypyridin-3-yl)-3-methyl-1-(4-(piperazin-1-yl)-3-(trifluoromethyl)phenyl)-1H-imidazo[4,5-c]quinolin-2(3H)-one Maleic a
Synonyms	BGT226 NVP-BGT226 BGT-226 maleate BGT226 (NVP-BGT226) 8-(6-Methoxypyridin-3-yl)-3-methyl-1-(4-(piperazin-1-yl)-3-(trifluoromethyl)phenyl)-1H-imidazo 8-(6-methoxypyridin-3-yl)-3-methyl-1-(4-(piperazin-1-yl)-3-(trifluoromethyl)phenyl)-1H-imidazo[4,5-c]quinolin-2(3H)-one Maleic a 8-(6-methoxypyridin-3-yl)-3-methyl-1-(4-(piperazin-1-yl)-3-(trifluoromethyl)phenyl)-1H-imidazo[4,5-c]quinolin-2(3H)-one Maleic acid 1-(3-(Trifluoromethyl)-4-(piperazin-1-yl)phenyl)-8-(6-methoxypyridin-3-yl)-3-methyl-1H-imidazo[4,5-c]quinolin-2(3H)-one maleic acid salt
CAS	1245537-68-1

NVP-BGT226 - Physico-chemical Properties

Molecular Formula	C28H25F3N6O2.C4H4O4
Molar Mass	650.6044696
Melting Point	>215°C (dec.)
Solubility	DMSO (Slightly)
Appearance	Solid
Color	White to Pale Yellow
Storage Condition	Hygroscopic, -20°C Freezer, Under inert atmosphere
In vitro study	Growth inhibition experiments showed that NVP-BGT226 had antitumor activity. NVP-BGT226 significantly inhibited cell growth with IC50 < 20 nM. NVP-BGT226 in the nanomolar concentration also induced apoptosis of cancer cells, IC50 <25 nM. NVP-BGT226 anti-proliferative and pro-apoptotic effects were independent of bcr-abl status. NVP-BGT226 inhibition of AKT/mTOR signaling pathway activation, this effect is concentration and time dependent. Flow cytometry analysis showed that cells accumulated in the G(0)-G(1) phase, followed by a decrease in the S phase. NVP-BGT226 effects on test cells, including SCC4, TU183 and KB cell lines, effectively inhibited growth with an IC50 of 7.4 to 30.1 nM. Treatment with PIK3CA mutant H1047R expressing Denoit 562 and alone -1 cells in NVP-BGT226 also effectively inhibited growth. In addition, the effect of NVP-BGT226 on alone -1 cells was comparable to that of anti-cisplatin cells. Glutp gap end labeling method (TUNEL) for terminal deoxynucleotidyl transferase regulation, and caspase 3/7 and PARP analysis, indicated that NVP-BGT226 induced cell death via the apoptotic pathway. NVP-BGT226 induction of autophagy by aggregation and upregulation of the microtubule-associated protein light chain 3B-II, and degradation of p62. Gene silencing of Beclin1 or treatment with an autophagosome inhibitor, 3-methylarenine, inhibited NVP-BGT226 of induced autophagy and restored colony survival. NVP-BGT226 inhibits growth at nanomolar concentrations on common myeloma cell lines and primary myeloma cells (e. G., NCI-H929, U266, RPMI-8226, and OPM2 multiple myeloma cell lines) in a time and dose dependent manner. NVP-BGT226 inhibition of protein kinase B(Akt), P70S6k and 4E-BP-1 phosphorylation was time-and dose-dependent. NVP-BGT226 completely inhibited the stimulatory effect of insulin-like growth factor 1, interleukin-6, and HS-5 stromal cell conditioned medium on myeloma cell growth. NVP-BGT226 can be used as a new candidate drug for the treatment of multiple myeloma. NVP-BGT226 effectively induce apoptosis and inhibit proliferation. The growth inhibition experiment showed that NVP-BGT226 had antitumor activity. NVP-BGT226 significantly inhibited cell growth with IC50 < 20 nM. NVP-BGT226 in the nanomolar concentration also induced apoptosis of cancer cells, IC50 <25 nM. NVP-BGT226 anti-proliferative and pro-apoptotic effects were independent of bcr-abl status. NVP-BGT226 inhibition of AKT/mTOR signaling pathway activation, this effect is concentration and time dependent. Flow cytometry analysis showed that cells accumulated in the G(0)-G(1) phase, followed by a decrease in the S phase. NVP-BGT226 effects on test cells, including SCC4, TU183 and KB cell lines, effectively inhibited growth with an IC50 of 7.4 to 30.1 nM. Treatment with PIK3CA mutant H1047R expressing Denoit 562 and alone -1 cells in NVP-BGT226 also effectively inhibited growth. In addition, the effect of NVP-BGT226 on alone -1 cells was comparable to that of anti-cisplatin cells. Glutp gap end labeling method (TUNEL) for terminal deoxynucleotidyl transferase regulation, And caspase 3/7 and PARP analysis, indicating that NVP-BGT226 induced cell death through the apoptotic pathway. NVP-BGT226 induction of autophagy by aggregation and upregulation of the microtubule-associated protein light chain 3B-II, and degradation of p62. Gene silencing of Beclin1 or treatment with an autophagosome inhibitor, 3-methylarenine, inhibited NVP-BGT226 of induced autophagy and restored colony survival. NVP-BGT226 inhibits growth at nanomolar concentrations on common myeloma cell lines and primary myeloma cells (e. G., NCI-H929, U266, RPMI-8226, and OPM2 multiple myeloma cell lines) in a time and dose dependent manner. NVP-BGT226 inhibition of protein kinase B(Akt), P70S6k and 4E-BP-1 phosphorylation was time-and dose-dependent. NVP-BGT226 completely inhibited the stimulatory effect of insulin-like growth factor 1, interleukin-6, and HS-5 stromal cell conditioned medium on myeloma cell growth. NVP-BGT226 can be used as a new candidate drug for the treatment of multiple myeloma. NVP-BGT226 effectively induce apoptosis and inhibit proliferation.
In vivo study	The effect of NVP-BGT226 on transplanted tumor animal model significantly delayed tumor growth in a dose-dependent manner, and was accompanied by p-p70 inhibition of S6 kinase cytoplasmic expression and autophagosome formation. NVP-BGT226 inhibited tumor growth in a FaDu cell xenograft model in a dose-dependent manner. Oral treatment at 2.5 and 5 mg/kg doses for three weeks in NVP-BGT226 resulted in a decrease in tumor growth of 34.7% and 76.1%, respectively, compared to the control group on day 21. NVP-BGT226 tumor growth inhibition was better than that of rapamycin. The final tumor volume of the NVP-BGT226 treatment group was significantly smaller than that of the LY294002 treatment group and the control group. NVP-BGT226 significantly delayed tumor growth in xenograft animal models in a dose-dependent manner and was accompanied by p-p70 inhibition of S6 kinase cytoplasmic expression and autophagosome formation. NVP-BGT226 inhibited tumor growth in a FaDu cell xenograft model in a dose-dependent manner. Oral treatment at 2.5 and 5 mg/kg doses for three weeks in NVP-BGT226 resulted in a decrease in tumor growth of 34.7% and 76.1%, respectively, compared to the control group on day 21. NVP-BGT226 tumor growth inhibition was better than that of rapamycin. The final tumor volume of the NVP-BGT226 treatment group was significantly smaller than that of the LY294002 treatment group and the control group.