GNE-9815

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

GNE-9815 是 RAF 的高激酶选择性抑制剂，通过联合疗法靶向 KRAS 突变癌症。

GNE-9815 is a high kinase-selective inhibitor of RAF and targets KRAS-mutant cancers through combination therapy.

GNE-9815 shows synergistic activity in KRAS mutant A549 and HCT116 cancer cells in combination with the MEK inhibitor Cobimetinib.

GNE-9815 (15 mg/kg; p.o.; single) demonstrates synergistic MAPK pathway modulation when combines with the MEK inhibitor Cobimetinib in an HCT116 xenograft mouse model.GNE-9815 (5 mg/kg; p.o.; single) shows good oral bioavailability and (1 mg/kg; i.v.; single) exhibits low blood clearance, moderate volume of distribution, and short half-life. Animal Model:Female NCR nude mice (6 to 8-week-old; 24-26 g; HCT116 xenograft mice model).Dosage:15 mg/kgAdministration:Intravenous injection or oral administration; single.Result:Resulted in pathway inhibition as demonstrated by partial inhibition of pRSK between 2 and 24 h, but more robust, albeit transient, inhibition of the downstream MAPK target genes, DUSP6 and SPRY4.Led to deeper inhibition of the downstream MAPK target genes DUSP6 and SPRY4, when combined with the MEK inhibitor Cobimetinib, with maximal inhibition at 8 h and with a more modest rebound in levels at 24 h, post final dose.Animal Model:Female NCR nude mice (6 to 8-week-old; 24-26 g).Dosage:1 mg/kg (for i.v.); 5 mg/kg (for p.o.).Administration:Intravenous injection or oral administration; single.Result:Exhibited CLb, Vdss and t1/2 values of 17 mL/min?kg, 1.7 L/kg and 1.9 h, respectively.Showed good oral bioavailability with F% of 37%. (methylcellulose/Tween formulation).

3-(2-cyanopropan-2-yl)-N-[2-fluoro-4-methyl-5-(7-methyl-8-oxo-7,8-dihydropyrido[2,3-d]pyridazin-3-yl)phenyl]benzamide

MAPK/ERK Signaling

Raf

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2729996-45-4

455.48

C26H22FN5O2

>98% (HPLC)

In Vitro:?DMSO : 50 mg/mL (109.77 mM)

N#CC(C=1C=CC=C(C1)C(=O)NC=2C=C(C3=CN=C4C(C=NN(C4=O)C)=C3)C(=CC2F)C)(C)C

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(-20℃)

With Ice Pack

≥ 2 years