KG5

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

KG5 是 PDGFRβ 和 B-Raf 的双重变构抑制剂，PDGFRβ 和 PDGFRα 的 Kd 分别为 520 nM 和 300 nM。 KG5 抑制 FLT3、KIT 和 c-Raf，具有抗癌和抗血管生成活性。

KG5 is a dual allosteric inhibitor of PDGFRβ and B-Raf with a Kd of 520 nM and 300 nM for PDGFRβ and PDGFRα. KG5 inhibits FLT3, KIT, and c-Raf with anticancer and antiangiogenic activities.(In Vitro):KG5 inhibits FLT3 and KIT at 52 and 170 nM, respectively. In endothelial cells stimulated with bFGF or VEGF, KG5 (5 μM) inhibits phosphorylation of MEK and ERK. KG5 inhibits vascular smooth muscle cells (VSMCs) and endothelial cell viability with EC50 values of 0.59 μM and 0.54 μM, respectively. KG5 selectively blocks S338 phosphorylation, yet does not influence S259.(In Vivo):KG5 (1 μM) disrupts a late step in angiogenesis during zebrafish embryogenesis. In male Nu/Nu mice injected with SN12C-RFP cells, KG5 (100 mg/kg; oral) prevents tumor growth. KG5 (50 mg/kg; i.p.) completely blocks angiogenesis in mice injected with Matrigel containing bFGF with a Cmax of 3.6 μg/mL, T1/2 of 11.5 h, and an AUC0-12h of 14.7 μg?h/mL.

KG5 (Compound 6) inhibits vascular smooth muscle cells (VSMCs) and endothelial cells viability with EC50 values of 0.59 μM and 0.54 μM, respectively.Compound 6 selectively blocks S338 phosphorylation, yet does not influence S259.KG5 (Compound 6) inhibits only PDGFRα and β with Kds of 300 and 520 nM, respectively, and Flt3 and KIT at 52 and 170 nM, respectively. KG5 (Compound 6; 5 μM) inhibits phosphorylation of MEK and ERK in endothelial cells stimulated with bFGF or VEGF.

KG5 (Compound 6; 100 mg/kg; oral administration; daily; for 26 days) treatment prevents tumor growth in an orthotopic renal cell carcinoma model.KG5 (Compound 6; 50 mg/kg; i.p.; twice daily) treatment completely blocks angiogenesis relative to vehicle control in mice (injected with Matrigel containing bFGF). Pharmacokinetic analysis of the dose and formulation of KG5 used indicated a Cmax of 3.6 μg/mL, T1/2 of 11.5 h, and an area under the concentration time curve (AUC0-12h) of 14.7 μg?h/mL.KG5 (Compound 6; 1 μM) disrupts a late step in angiogenesis during zebrafish embryogenesis. Animal Model:Male Nu/Nu mice injected with SN12C-RFP cells Dosage:100 mg/kg Administration:Oral administration; daily; for 26 daysResult:Prevented tumor growth in an orthotopic renal cell carcinoma model.

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MAPK/ERK Signaling

Raf

TLR8

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877874-85-6

459.45

C20H16F3N7OS

>98% (HPLC)

In Vitro:?DMSO : 100 mg/mL (217.65 mM)

FC(F)(F)C=1C=CC=C(C1)NC2=NN=C(N2)C=3C=CC(OC4=NC(=NC(N)=C4)SC)=CC3

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(-20℃)

With Ice Pack

≥ 2 years