Larotrectinib sulfate

Larotrectinib sulfate (LOXO-101 sulfate; ARRY-470 sulfate) is an ATP-competitive oral, selective inhibitor of the tropomyosin-related kinase (TRK) family receptors, with low nanomolar 50% inhibitory concentrations against all three isoforms (TRKA, B, and C).

Product information

CAS Number: 1223405-08-0

Molecular Weight: 526.51

Formula: C21H24F2N6O6S

Chemical Name: (3S)-N-{5-[(2R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl}-3-hydroxypyrrolidine-1-carboxamide; sulfuric acid

Smiles: O[C@H]1CCN(C1)C(=O)NC1C=NN2C=CC(=NC2=1)N1CCC[C@@H]1C1=CC(F)=CC=C1F.OS(O)(=O)=O

InChiKey: PXHANKVTFWSDSG-QLOBERJESA-N

InChi: InChI=1S/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+;/m0./s1

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO : 50 mg/mL (94.96 mM; Need ultrasonic). H2O : 2 mg/mL (3.80 mM; ultrasonic and adjust pH to 2 with 1M HCl).

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

Larotrectinib (LOXO-101) is an ATP-competitive oral inhibitor of the tropomyosin-related kinase (TRK) family of receptor kinases (TRKA, B, and C), with low nanomolar 50% inhibitory concentrations against all three isoforms, and 1,000-fold or greater selectivity relative to other kinases. Measurement of proliferation following treatment with Larotrectinib (LOXO-101) demonstrates a dose-dependent inhibition of cell proliferation in all three cell lines. The IC50 is less than 100 nM for CUTO-3.29 and less than 10 nM for KM12 and MO-91 consistent with the known potency of this drug for the TRK kinase family.

In Vivo:

In rat and monkey studies, Larotrectinib (LOXO-101) demonstrates 33-100% oral bioavailability and 60-65% plasma protein binding. It has low brain penetration, and is well tolerated in 28 day (d) GLP toxicology studies. A single dose (30 mg/kg) of Larotrectinib (LOXO-101) reduces tyrosine phosphorylation of TRKA and downstream signal transduction (pERK) in the tumor >80%. Athymic nude mice injected with KM12 cells are treated with Larotrectinib sulfate orally daily for 2 weeks. Dose-dependent tumor inhibition is observed demonstrating the ability of this selective compound to inhibit tumor growth in vivo. Larotrectinib (LOXO-101) (200mg/kg/day p.o for six weeks) reduces leukemic infiltration to undetectable levels in the bone marrow and spleen compared to vehicle-treated mice. Mice treated with Larotrectinib sulfate are still alive and leukemia-free four weeks after the cessation of treatment, as determined by Xenogen imaging.

Products are for research use only. Not for human use.