1223405-08-0 Usage
Solubility
LOXO-101 (sulfate) ?can be dissolved in DMSO(Slightly), Methanol (Slightly, Sonicated), Water (Slightly) .
Description
LOXO-101 (sulfate) is an orally bioavailable, potent, ATP-competitive inhibitor of TRKA, TRKB, and TRKC. LOXO-101 has IC50 values in the low nanomolar range for inhibition of all three TRK family members in binding and cellular assays, with 100x selectivity over other kinases, and has shown acceptable pharmaceutical properties and safety in nonclinical models. The TRK family of neurotrophin receptors, TRKA, TRKB, and TRKC (encoded by NTRK1, NTRK2, and NTRK3 genes, respectively) and their neurotrophin ligands regulate growth, differentiation and survival of neurons.
Uses
Larotrectinib Sulfate is a potent and selective oral ATP-competitive inhibitor of tropomyosin receptor kinases (TRK).
in vitro
in previous study, loxo-101 was evaluated for off-target kinase enzyme inhibition against a panel of non-trk kinases at a concentration of 1,000 nm and atp concentrations around the km. results showed that loxo-101 had greater than 50% inhibition for only one non-trk kinase, which was tnk2 with ic50 of 576 nm. moreover, there were neither relevant herg inhibition nor prolonged qt observation [1].
in vivo
animal study found that loxo-101 was able to inhibit in vivo tumor growth. athymic nude mice injected with km12 cells were orally treated with loxo-101 daily for 2 weeks, and dose-dependent tumor inhibition was observed, indicating the ability of loxo-101 to inhibit in-vivo tumor growth [1].
IC 50
low nanomolar range for inhibition of all trk family members
references
[1] doebele rc et al. an oncogenic ntrk fusion in a patient with soft-tissue sarcoma with response to the tropomyosin-related kinase inhibitor loxo-101. cancer discov.2015 oct;5(10):1049-57.
Check Digit Verification of cas no
The CAS Registry Mumber 1223405-08-0 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,2,2,3,4,0 and 5 respectively; the second part has 2 digits, 0 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 1223405-08:
(9*1)+(8*2)+(7*2)+(6*3)+(5*4)+(4*0)+(3*5)+(2*0)+(1*8)=100
100 % 10 = 0
So 1223405-08-0 is a valid CAS Registry Number.
1223405-08-0Relevant articles and documents
Assignment of NMR data and Conformational analysis of larotrectinib and its precursors
Lv, Xunlei,Zheng, Yan,Pan, Jing,Chen, Liang,Lin, Kuaile,Ye, Deyong,Zhou, Weicheng
, (2021/03/18)
NMR experiments were used to identify the two main conformations of Larotrectinib and its synthetic precursor, the nitro compound 4. Conformational analysis by dynamic NMR was performed in different temperature and solvents, combining 2D EXSY and NOE expe
SUBSTITUTED PYRAZOLO[1,5-a]PYRIMIDINE COMPOUNDS AS TRK KINASE INHIBITORS
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Page/Page column 60, (2010/05/13)
Compounds of Formula (I) in which R1, R2, R3, R4, X, Y and n have the meanings given in the specification, are inhibitors of Trk kinases and are useful in the treatment of diseases which can be treated with a Trk kinase inhibitor.
