Selitrectinib 是二代原肌凝蛋白相关激酶(TRK)抑制剂，能够作用于 TRKA (IC50:0.6 nM) 和 TRKC (IC50<2.5 nM)。

Selitrectinib is a potent and selective inhibitor of the receptor tyrosine kinases(TRK)( TrkA and TrkC with IC50s of 0.6 and<2.5 nM, respectively)

Selitrectinib (≥30 mg/kg) reduces tumor growth in TrkA-dependent KM12, as well as NIH 3T3 ΔTrkA, ΔTrkA + TrkAG595R, and ΔTrkA + TrkAG667C mouse xenograft models.

Each cell line (2–5×10e6 cells) was injected subcutaneously into female nu/nu NCr mice age 7–9 weeks and allowed to grow to ~100–200 mm3 (efficacy) or ~ 500mm3 (PK-PD) prior to randomization by tumor size and treatment with each inhibitor by oral gavage.?For PK-PD analysis, animals were dosed for 3 days, followed by euthanasia, excision of tumors and collection of plasma.?Phospho-TRK levels in tumor lysates were determined by ELISA assay, while plasma inhibitor levels were determined by LC-MS/MS.?For efficacy analysis, animals were dosed by oral gavage, and body weight and tumor size were monitored at regular intervals.

2097002-61-2

C20H21FN6O

380.427

LOXO-195

DMSO:62.5 mg/mL (164.29 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years