LPM4870108

发表于由

上海金畔生物科技有限公司为生命科学和医药研发人员提供生物活性分子抑制剂、激动剂、特异性抑制剂、化合物库、重组蛋白，专注于信号通路和疾病研究领域。

LPM4870108 

LPM4870108 是一种有效且具有口服活性的泛 Trk (WT/MT) 抑制剂，对 TrkC，TrkA，TrkAG595R 和 TrkAG667C 的 IC50 分别为 0.2 nM、2.4 nM、3.5 nM 和 2.3 nM。LPM4870108 显示了对 Trk 的选择性超过 ALK (IC50=182 nM)。LPM4870108 具有抗肿瘤活性。

LPM4870108

LPM4870108 Chemical Structure

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生物活性

LPM4870108 is a potent and orally active pan-Trk (WT and MT) inhibitor, with IC50s of 0.2 nM, 2.4 nM, 3.5 nM and 2.3 nM for TrkC, TrkA, TrkAG595R and TrkAG667C, respectively. LPM4870108 shows selectivity for Trk over ALK (IC50=182 nM). LPM4870108 exhibits anti-tumor activity[1][2].

IC50 & Target[1]

TrkC

0.2 nM (IC50)

TrkA

2.4 nM (IC50)

体外研究
(In Vitro)

LPM4870108 (compound 10) inhibits the activities of TrkA, TrkB, and TRC with high selectivity at 0.5 μM (kinase activity remaining, <10%) and slightly inhibit the activities of ALK and ROS1 (kinase activity remaining, 10-30%)[1].

Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究
(In Vivo)

LPM4870108 (compound 10) (5-20 mg/kg; p.o. once daily for 21 days) inhibits tumor growth in BaF3-NTRK xenograft tumor models[1].
LPM4870108 (2 mg/kg; a single i.v.) exhibits terminal half-life (t1/2) (male 0.87 h, 2.21 h), the Cl (male 19.3 mL/kg/min, female 8.19 mL/kg/min), and the AUC0-t (male 4191 nM•h, female 10282 nM•h) in rats[1].
LPM4870108 (10 mg/kg; a single p.o.) exhibits oral bioavailability (male 56.0%, female 61.9%), Cmax (male 6384 nM, female 6628 nM) and Tmax (male 0.667 h, female 0.667 h) in rats[1].

Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: Mice bearing 100-200 mm3 BaF3-NTRK tumors[1]
Dosage: 5, 10, 20 mg/kg
Administration: P.o. once daily for 21 days
Result: Showed slight weight loss and all animals survived at the highest dose.
Animal Model: Sprague-Dawley rats (six males and six females)[1]
Dosage: 2 mg/kg for i.v.; 10 mg/kg for oral (Pharmacokinetic Analysis)
Administration: Intravenous administration and oral administration
Result: I.v.: t1/2 (male 0.87 h, 2.21 h), Cl (male 19.3 mL/kg/min, female 8.19 mL/kg/min), AUC0-t (male 4191 nM•h, female 10282 nM•h).
P.o.: F (male 56.0%, female 61.9%), Cmax (male 6384 nM, female 6628 nM), Tmax (male 0.667 h, female 0.667 h).

分子量

410.40

Formula

C20H19FN6O3
运输条件

Room temperature in continental US; may vary elsewhere.
储存方式

Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献

  • [1]. Liu Z, et, al. Discovery of the Next-Generation Pan-TRK Kinase Inhibitors for the Treatment of Cancer. J Med Chem. 2021 Jul 22;64(14):10286-10296.

    [2]. Duan S, et, al. Assessment of the toxicity and toxicokinetics of the novel potent tropomyosin receptor kinase (Trk) inhibitor LPM4870108 in rhesus monkeys. Regul Toxicol Pharmacol. 2021 Jun;122:104886.

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