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.
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- CAS No.: 2803679-07-2
- Formule: C20H19FN6O3
- Masse moléculaire:410.40
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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Chemical Information
- Pureté et documentation
- Références
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Help & FAQs
Activité biologique
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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
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[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
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[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).
Chemical Information
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CAS No. 2803679-07-2
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Masse moléculaire 410.40
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Formule 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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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
[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
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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