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LOXO-101

In stock
Catalog No.
B6176
tropomyosin receptor kinases (TRK) inhibitor
Grouped product items
SizePriceStock Qty
5mg
$68.00
In stock
25mg
$208.00
In stock
100mg
$558.00
In stock

Background

IC50: low nanomolar range for inhibition of all TRK family members

LOXO-101 is a tropomyosin receptor kinases (TRK) inhibitor.

The TRK family of neurotrophin receptors and their neurotrophin ligands regulate neuron growth, differentiation and survival.

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].

Clinical trial: A multicenter phase I dose-escalation study in patients with advanced solid tumors (ClinicalTrials.gov no. NCT02122913) was conducted in 2014 to evaluate the safety and PK of LOXO-101. Patients are dosed once or twice daily for 28 days of continuous dosing in escalating cohorts. Preliminary PK and safety data indicate that the free plasma levels of LOXO-101 are at biologically relevant concentrations to inhibit TRK oncogenes. In this study, the first and only patient showed TRK fusion and the rapid clinical tumor regression seen with the treatment of LOXO-101 [1].

Reference:
[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.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt526.51
Cas No.1223405-08-0
FormulaC21H24F2N6O6S
SynonymsLarotrectinib
SolubilitySoluble in DMSO
Chemical Name(S)-N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide sulfate
SDFDownload SDF
Canonical SMILESO=S(O)(O)=O.O=C(N1C[[email protected]@H](O)CC1)NC2=C3N=C(N4[[email protected]@H](C5=CC(F)=CC=C5F)CCC4)C=CN3N=C2
Shipping ConditionEvaluation sample solution : ship with blue ice.All other available size: ship with RT , or blue ice upon request
General tipsFor obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.

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