Larotrectinib sulfate 是一种 ATP 竞争性的，口服选择性抑制剂，对原肌凝蛋白相关激酶家族受体的三个亚型具有纳摩尔级别的 50% 抑制浓度。

LOXO-101 is an oral active and specific ATP-competitive inhibitor of tropomyosin receptor kinases (TRK).

LOXO-101(ARRY-470) is a specific kinase inhibitor with nanomolar activity against TRKA/TRKB/TRKC but no other notable kinase inhibition (1 μM). ARRY-470 hasn't the inhibitory of the proliferation of Ba/F3 cells expressing other oncogene targets (EGFR, ROS1 or ALK) or of lung and colorectal cell lines that do not harbor an NTRK1 fusion. It induces cell-cycle arrest in G1 and apoptosis of KM12 cells.

Early/sustained but not late/acute administration of ARRY-470(LOXO-101) obviously attenuates bone cancer pain and blocks the ectopic sprouting of sensory nerve fibers and the formation of neuroma-like structures in the tumor-bearing bone, but no significant inhibition for tumor growth or bone remodeling. It has very limited ability crossing of the blood-brain barrier.

Concentrations: 10,100,1000 nM. Method: Ba/F3 cells expressing MPRIP-NTRK1 (RIP-TRKA) or EV were lysed after 5 h of treatment with the indicated doses of drugs (ARRY-470; G,gefitinib 1,000 nM) or DMSO control.The cell lysate is used for western blot analysis.

Animal Models: Adult male C3H/HeJ mice. Formulation: Labrafac; polygly-colyzed glyceride. Dosages: 10-100 mg/kg. Administration: p.o.

1223405-08-0

C21H24F2N6O6S

526.52

Larotrectinib;LOXO-101 sulfate;Larotrectinib (LOXO-101) sulfate;LOXO-101 (sulfate);ARRY-470;ARRY-470 (sulfate)

H2O:<1 mgml
DMSO:93 mg/mL (176.6 mM)
Ethanol:10 mg/mL(19 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years