Larotrectinib Sulfate Chemical Properties

storage temp. 

Store at -20°C

solubility 

≥18.47 mg/mL in DMSO; ≥2.14 mg/mL in EtOH; ≥29.65 mg/mL in H2O

form 

solid

color 

Light yellow to brown

Stability:

Hygroscopic

InChI

InChI=1/C21H22F2N6O2.H2O4S/c22-13-3-4-16(23)15(10-13)18-2-1-7-28(18)19-6-9-29-20(26-19)17(11-24-29)25-21(31)27-8-5-14(30)12-27;1-5(2,3)4/h3-4,6,9-11,14,18,30H,1-2,5,7-8,12H2,(H,25,31);(H2,1,2,3,4)/t14-,18+;/s3

InChIKey

PXHANKVTFWSDSG-RZOMTXEQNA-N

SMILES

S(O)(O)(=O)=O.FC1C=CC(F)=CC=1[C@H]1CCCN1C1C=CN2N=CC(NC(N3C[C@@H](O)CC3)=O)=C2N=1 |&1:13,29,r|

Larotrectinib Sulfate Usage And Synthesis

Solubility

LOXO-101 (sulfate)  can be dissolved in DMSO(Slightly), Methanol (Slightly, Sonicated), Water (Slightly) .

Description

LOXO-101 (sulfate) (or Larotrectinib Sulfate)  is an oral potent and selective ATP-competitive inhibitor of tropomyosin receptor kinases (TRK). 

Uses

Larotrectinib Sulfate is a potent and selective oral ATP-competitive inhibitor of tropomyosin receptor kinases (TRK).

Mechanism of action

Larotrectinib sulfate functions as an inhibitor of TRKs including TRKA, B, and C. In in vitro and in vivo tumor models, larotrectinib demonstrated anti-tumor activity in cells with constitutive activation of TRK proteins resulting from gene fusions, deletion of a protein regulatory domain, or in cells with TRK protein overexpression. Larotrectinib had minimal activity in cell lines with point mutations in the TRKA kinase domain, including the clinically identified acquired resistance mutation, G595R. Point mutations in the TRKC kinase domain with clinically identified acquired resistance to larotrectinib include G623R, G696A, and F617L.

Clinical Use

Larotrectinib sulfate is approved to treat solid tumors with NTRKgene fusion without drug resistance mutation in specific TRK proteins. It is used in adults and children whose cancer has metastasized (spread to other parts of the body) or cannot be removed by surgery and has gotten worse after other treatments or cannot be treated with other therapies. This use is approved under FDA’s Accelerated Approval Program. As a condition of approval, a confirmatory trial(s) must show that larotrectinib sulfate provides a clinical benefit in these patients. Larotrectinib sulfate is also being studied in treating other types of cancer.

in vitro

in previous study, loxo-101 (Larotrectinib Sulfate) 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 (Larotrectinib Sulfate) 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.

Larotrectinib Sulfate(1223405-08-0)Related Product Information

• PRND
• LOXO-101
• BMN 673