产品
编 号：F754638
分子式：C28H25ClFN7O2
分子量：546
分子式：C28H25ClFN7O2
分子量：546
产品类型
规格
价格
是否有货
10mM*1mL in DMSO
询价
询价
5mg
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10mg
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25mg
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询价
结构图
CAS No: 2688040-45-9
产品详情
生物活性：
Lirafugratinib (RLY-4008) hydrochloride is an orally active, irreversible and highly selective FGFR2 inhibitor with an IC50 of 3 nM. Lirafugratinib hydrochloride covalently binds to Cys491. Lirafugratinib hydrochloride targets FGFR2 primary alterations and resistance mutations and induces tumor regression while sparing other FGFRs.
体内研究：
Lirafugratinib (RLY-4008；1-30 mg/kg；口服灌胃，每天两次；15-30 天) hydrochloride 在 FGFR2 改变的癌症异种移植模型中表现出抗肿瘤活性。Animal Model:Female BALB/c nude mice with SNU-16 and AN3CA xenografts; female NOD SCID mice with CC13-7 and ICC13-7-FGFR2V564F xenografts
Dosage:1, 3, 10, 30 mg/kg
Administration:Orally; twice daily; for 15-30 days
Result:Exhibited dose-dependent antitumor activity and induced tumor regression in all models.
体外研究：
Lirafugratinib (RLY-4008) hydrochloride 对 FGFR2 的选择性比 FGFR1 高 250 倍，比 FGFR3 和 FGFR4 的选择性分别高 80 倍和 5,000 倍。Lirafugratinib hydrochloride 的可逆结合促进 FGFR1 中刚性且延伸的 P 环，不利于共价键形成，同时最大限度地影响 FGFR2 中 P 环的构象，从而实现有效的共价键形成并导致 FGFR2 选择性。Lirafugratinib (24 小时) hydrochloride 诱导 caspase-3 和聚 (ADP-核糖) 聚合酶 (PARP) (凋亡早期标志物)的剂量依赖性裂解。Lirafugratinib (2 小时) hydrochloride 剂量依赖性降低 FGFR2 信号通路节点 (包括 FRS2、AKT 和 ERK) 磷酸化。RLY-4008 hydrochloride 抑制 FGFR2 依赖性细胞系 (包括 KATO III、SNU-16 和 NCI-H716、ICC13-7 和 MFE-296、FGFR2N549K 和 AN3CA、FGFR2K310R 和 N549K 和 JHUEM-2、FGFR2C383R) 的增殖，IC50Lirafugratinib hydrochloride 相关抗体:Apoptosis AnalysisCell Line:FGFR2-amplified gastric cancer cell line SNU-16
Concentration:IC50 (6 nM), IC90
Incubation Time:24 h
Result:Induced dose-dependent cleavage of caspase-3 and poly (ADP-ribose) polymerase (PARP)-early markers of apoptosis.
Apoptosis AnalysisCell Line:FGFR2-amplified gastric cancer cell line SNU-16
Concentration:IC50 (6 nM), IC90
Incubation Time:2 h
Result:Demonstrated a dose-dependent reduction of phosphorylation of FGFR2 signaling pathway nodes, including FRS2, AKT, and ERK.
Lirafugratinib (RLY-4008) hydrochloride is an orally active, irreversible and highly selective FGFR2 inhibitor with an IC50 of 3 nM. Lirafugratinib hydrochloride covalently binds to Cys491. Lirafugratinib hydrochloride targets FGFR2 primary alterations and resistance mutations and induces tumor regression while sparing other FGFRs.
体内研究：
Lirafugratinib (RLY-4008；1-30 mg/kg；口服灌胃，每天两次；15-30 天) hydrochloride 在 FGFR2 改变的癌症异种移植模型中表现出抗肿瘤活性。Animal Model:Female BALB/c nude mice with SNU-16 and AN3CA xenografts; female NOD SCID mice with CC13-7 and ICC13-7-FGFR2V564F xenografts
Dosage:1, 3, 10, 30 mg/kg
Administration:Orally; twice daily; for 15-30 days
Result:Exhibited dose-dependent antitumor activity and induced tumor regression in all models.
体外研究：
Lirafugratinib (RLY-4008) hydrochloride 对 FGFR2 的选择性比 FGFR1 高 250 倍，比 FGFR3 和 FGFR4 的选择性分别高 80 倍和 5,000 倍。Lirafugratinib hydrochloride 的可逆结合促进 FGFR1 中刚性且延伸的 P 环，不利于共价键形成，同时最大限度地影响 FGFR2 中 P 环的构象，从而实现有效的共价键形成并导致 FGFR2 选择性。Lirafugratinib (24 小时) hydrochloride 诱导 caspase-3 和聚 (ADP-核糖) 聚合酶 (PARP) (凋亡早期标志物)的剂量依赖性裂解。Lirafugratinib (2 小时) hydrochloride 剂量依赖性降低 FGFR2 信号通路节点 (包括 FRS2、AKT 和 ERK) 磷酸化。RLY-4008 hydrochloride 抑制 FGFR2 依赖性细胞系 (包括 KATO III、SNU-16 和 NCI-H716、ICC13-7 和 MFE-296、FGFR2N549K 和 AN3CA、FGFR2K310R 和 N549K 和 JHUEM-2、FGFR2C383R) 的增殖，IC50Lirafugratinib hydrochloride 相关抗体:Apoptosis AnalysisCell Line:FGFR2-amplified gastric cancer cell line SNU-16
Concentration:IC50 (6 nM), IC90
Incubation Time:24 h
Result:Induced dose-dependent cleavage of caspase-3 and poly (ADP-ribose) polymerase (PARP)-early markers of apoptosis.
Apoptosis AnalysisCell Line:FGFR2-amplified gastric cancer cell line SNU-16
Concentration:IC50 (6 nM), IC90
Incubation Time:2 h
Result:Demonstrated a dose-dependent reduction of phosphorylation of FGFR2 signaling pathway nodes, including FRS2, AKT, and ERK.
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