In vitro: Larotrectinib (LOXO-101) was evaluated for off-target kinase enzyme inhibition against a panel of 226 non-TRK kinases at a compound concentration of 1,000 nM and ATP concentrations near the Km for each enzyme. LOXO-101 demonstrated greater than 50% inhibition for only one non-TRK kinase (TNK2 IC50 = 576 nM).
In vivo: A single dose (30 mg/kg) of LOXO-101 reduced tyrosine phosphorylation of TRKA and downstream signal transduction (pERK) in the tumor >80%. LOXO-101 was well tolerated up to 200 mg/kg/day for 14 d in this model.
Br J Cancer. 2023 Mar 23.
Functional genomics of human clear cell sarcoma: genomic, transcriptomic and chemical biology landscape for clear cell sarcoma
Larotrectinib (LOXO-101) purchased from AbMole
Clin Transl Med. 2022 Jul;12(7):e961.
Functional genomic analysis of epithelioid sarcoma reveals distinct proximal and distal subtype biology
Larotrectinib (LOXO-101) purchased from AbMole
 |
Source | Cancer Discov (2015). Figure 1. LOXO-101 |
| Method | MTS assay | |
| Cell Lines | CUTO-3.29 cells | |
| Concentrations | 100 nM | |
| Incubation Time | 2 h | |
| Results | pAKT was not inhibited in the CUTO-3.29 cells by LOXO-101 suggesting that TRK signaling is not AKT-dependent in this tumor. |
| Cell Experiment | |
|---|---|
| Cell lines | KM12 cells |
| Preparation method | Dose-dependent inhibition with LOXO-101 is demonstrated in three cancer cell line models of oncogenic TRK. |
| Concentrations | 100 nM |
| Incubation time | 24h |
| Animal Experiment | |
|---|---|
| Animal models | Athymic nude mice |
| Formulation | |
| Dosages | 60 mg/kg |
| Administration | oral gavage |
| Molecular Weight | 428.44 |
| Formula | C21H22F2N6O2 |
| CAS Number | 1223403-58-4 |
| Solubility (25°C) | DMSO 4.3 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
| Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
| Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
| Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
| Related Trk Products |
|---|
| Cyclotraxin B
Cyclotraxin B, a cyclic peptide, is a highly potent and selective TrkB inhibitor without altering the binding of BDNF. |
| Gambogic amide
Gambogic amide is a potent and selective agonist of TrkA and also induces its tyrosine phosphorylation and activation of downstream signaling, including Akt and MAPK. |
| Protein kinase inhibitor 4
Protein kinase inhibitor 4 is a protein kinase inhibitor that inhibits TRK-A and ROS1 (IC50=3.0 nM and 104 nM respectively). |
| TRK-IN-22
TRK-IN-22 is a TRK inhibitor. |
| TrkB-IN-1
TrkB-IN-1 is a potent and orally active TrkB agonist and has favorable PK properties. |
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2023 AbMole BioScience. All Rights Reserved.
