Uses
GNF 7 inhibits ras signaling, Ack1 and germinal center kinase (GCK). Also, it suppresses proliferation, and induces cell cycle arrest and apoptosis in leukemia cells harboring NRAS mutations. It is a COVID19-related research product.
Biological Activity
gnf-7 is the type-ii inhibitor of t315i-bcr-abl [1]. bcr-abl, constitutively activated tyrosine kinase, is an oncogene associated with chronic myelogenous leukemia (cml) and some cases ofacute lymphocytic leukemia in humans.
in vitro
gnf-7 showed excellent growth inhibitory activity against some human cancer cells. the ic50 of gnf-7is 0.005, 0.001, and 0.008 μm when tested in colo205, sw620, and trkc-ba/f3 cell line, respectively.gnf-7 showed little effect on hek293t cells, a normal cell line [1].after treated for 24h (7.5mg/kg qd or 15 mg/kg qd), gnf-7 significantly decreaseddisease burden in mice and prolonged overall survival compared to vehicle-controls [2].
in vivo
in acute myelogenous leukemia and lymphoblastic leukemia models, gnf-7 potently and selectively inhibited nras-dependent cells [2]. in thet315i-bcr-abl-ba/f3 cell line bioluminescent xenograft mouse model,oral administration of gnf-7 with 10or20mg/kgexhibited significant efficacy against t315i-bcr-abl without appreciable toxicity [1].
IC 50
the ic50 of gnf-7is 0.005, 0.001, and 0.008 μm in colo205, sw620, and trkc-ba/f3 cells, respectively.
References
choi h g, ren p, adrian f, et al. a type-ii kinase inhibitor capable of inhibiting the t315i “gatekeeper” mutant of bcr-abl[j]. journal of medicinal chemistry, 2010, 53(15): 5439-5448.nonami a, sattler m, weisberg e, et al. identification of novel therapeutic targets in acute leukemias with nras mutations using a pharmacologic approach[j]. blood, 2015, 125(20): 3133-3143.
