LPM4870108
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.
商品は「研究用試薬」です。人や動物の医療用・臨床診断用・食品用の製品ではありません。
研究用途以外に使用した場合、当社は一切の責任を負いかねます。
- CAS 番号: 2803679-07-2
- 分子式: C20H19FN6O3
- 分子量:410.40
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保管条件:
Please store the product under the recommended conditions in the Certificate of Analysis.
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生物活性
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化学情報
- 純度とドキュメンテーション
- 参考文献
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Help & FAQs
生物活性
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TrkC 0.2 nM (IC50) |
TrkA 2.4 nM (IC50) |
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| BaF3 | IC50 |
0.6 nM
Compound: 10; LPM4870108
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Cytotoxicity against mouse BaF3 cells transfected with TrKA assessed as reduction in cell viability by MTT assay
Cytotoxicity against mouse BaF3 cells transfected with TrKA assessed as reduction in cell viability by MTT assay
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[PMID: 34253025] |
| BaF3 | IC50 |
0.8 nM
Compound: 10; LPM4870108
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Cytotoxicity against mouse BaF3 cells transfected with TrKA G667A mutant assessed as reduction in cell viability by MTT assay
Cytotoxicity against mouse BaF3 cells transfected with TrKA G667A mutant assessed as reduction in cell viability by MTT assay
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[PMID: 34253025] |
| BaF3 | IC50 |
2.3 nM
Compound: 10; LPM4870108
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Cytotoxicity against mouse BaF3 cells transfected with SLC34A2-Ros1 assessed as reduction in cell viability by MTT assay
Cytotoxicity against mouse BaF3 cells transfected with SLC34A2-Ros1 assessed as reduction in cell viability by MTT assay
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[PMID: 34253025] |
| BaF3 | IC50 |
2.7 nM
Compound: 10; LPM4870108
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Cytotoxicity against mouse BaF3 cells transfected with TrKA G623R mutant assessed as reduction in cell viability by MTT assay
Cytotoxicity against mouse BaF3 cells transfected with TrKA G623R mutant assessed as reduction in cell viability by MTT assay
|
[PMID: 34253025] |
| BaF3 | IC50 |
4.9 nM
Compound: 10; LPM4870108
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Cytotoxicity against mouse BaF3 cells transfected with TrKA F589L mutant assessed as reduction in cell viability by MTT assay
Cytotoxicity against mouse BaF3 cells transfected with TrKA F589L mutant assessed as reduction in cell viability by MTT assay
|
[PMID: 34253025] |
| BaF3 | IC50 |
7.7 nM
Compound: 10; LPM4870108
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Cytotoxicity against mouse BaF3 cells transfected with TrKA G595R mutant assessed as reduction in cell viability by MTT assay
Cytotoxicity against mouse BaF3 cells transfected with TrKA G595R mutant assessed as reduction in cell viability by MTT assay
|
[PMID: 34253025] |
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].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Mice bearing 100-200 mm3 BaF3-NTRK tumors[1]
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Dosage:5, 10, 20 mg/kg
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Administration:P.o. once daily for 21 days
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Result:Showed slight weight loss and all animals survived at the highest dose.
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Animal Model:Sprague-Dawley rats (six males and six females)[1]
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Dosage:2 mg/kg for i.v.; 10 mg/kg for oral (Pharmacokinetic Analysis)
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Administration:Intravenous administration and oral administration
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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).
化学情報
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CAS 番号 2803679-07-2
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分子量 410.40
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分子式 C20H19FN6O3
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SMILES
O=C1C2=C3N(C=CC(N4[C@@H](C5=CC(F)=CN=C5OCC6(N1)CC6)COCC4)=N3)N=C2
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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
Please store the product under the recommended conditions in the Certificate of Analysis.
純度とドキュメンテーション
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. [Content Brief]
[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. [Content Brief]
Calculators
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
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