GNF-7

Research use only, not for human use.

A potent and selective type-II kinase inhibitor of Bcr-Abl.

A potent and selective type-II kinase inhibitor of Bcr-Abl; inhibits wt Bcr-Abl/T315I Bcr-Abl (IC50< 5 nM) and Bcr-Abl mutants such as G250E, Q252H, Y253H, E255K, E255V, F317L, and M351T in biochemical and cellular assays; displays in vivo efficacy against T315I-Bcr-Abl in xenograft mouse model.

Western Blot Analysis Cell Line:Ba/F3-NRAS-G12D cells, OCI-AML3 cells Concentration:1 μM Incubation Time:2 hours Result:Caused a decreased level of phosphorylation of p70S6K1, AKT (S473), JNK, and p38.Apoptosis Analysis Cell Line:OCI-AML3 cells Concentration:1 μM Incubation Time:24 hours Result:Increased the levels of both cleaved PARP and cleaved caspase 3 and diminished bcl-2 and MCL1.Cell Cycle Analysis Cell Line:OCI-AML3 cells Concentration:1 μM Incubation Time:24 hoursResult:Induced of G0-G1 arrest.

Animal Model:6-8 weeks old SCID beige female mice, with Ba/F3-T315I-Bcr-Abl cells xenograft Dosage:10 mg/kg, 20 mg/kg Administration:Oral administration, daily, for 7 days Result:Effectively inhibited tumor growth of T315I-Bcr-Abl-Ba/F3 cells in mice at low doses (10 mg/kg). Animal Model:5-6 weeks old male Balb/c mice (20-25 g) Dosage:5 mg/kg for i.v.; 20 mg/kg for i.g. (Pharmacokinetic Analysis)Administration:Intravenous injection and oral gavage Result:Oral bioavailability (36%), Cmax (3616 nM), T1/2 (3.2 h).

GNF 7 | GNF7

Angiogenesis

Bcr-Abl

c-Abl|E255V|G250E|M351T|T315I

Cancer

——

839706-07-9

547.5311

C28H24F3N7O2

>98% (HPLC)

DMSO: ≥ 33 mg/mL

O=C(NC1=CC=C(C)C(N2CC3=CN=C(NC4=CC=C(C)N=C4)N=C3N(C)C2=O)=C1)C5=CC=CC(C(F)(F)F)=C5

Benzamide, N-[3-[1,4-dihydro-1-methyl-7-[(6-methyl-3-pyridinyl)amino]-2-oxopyrimido[4,5-d]pyrimidin-3(2H)-yl]-4-methylphenyl]-3-(trifluoromethyl)-

(-20℃)

With Ice Pack

≥ 2 years