In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
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 .
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 .
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 .
 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.
|Physical Appearance||A solid|
|Storage||Store at -20°C|
|Solubility||Soluble 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|
|Canonical SMILES||O=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 Condition||Evaluation sample solution : ship with blue ice.All other available size: ship with RT , or blue ice upon request|
|General tips||For 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.|