1223405-08-0

Basic information

• Product Name: LOXO-101 (sulfate)
• Synonyms: LOXO-101 (sulfate);(3S)-N-[5-[(2R)-2-(2,5-Difluorophenyl)-1-pyrrolidinyl]pyrazolo[1,5-a]pyrimidin-3-yl]-3-hydroxy-1-pyrrolidinecarboxamide sulfate (1:1);Larotrectinib/LOXO 101/ARRY 470 sulfate;(3S)-N-[5-[(2R)-2-(2,5-Difluorophenyl)-1-pyrrolidinyl]pyrazolo[1,5-a]pyrimidin-3-yl]-3-hydroxy-1-pyrrolidinecarboxamide sulfate;ARRY 470) sulfate;Larotrectinib sulfate;Larotrectinib(LOXO 101;Larotrectinib (LOXO-101) sulfate
• CAS NO: 1223405-08-0
• Molecular Formula: C₂₁H₂₂F₂N₆O₂*H₂O₄S
• Molecular Weight: 526.5136664
• EINECS: 232-655-5
• Product Categories: API;LOXO-101
• Mol File: 1223405-08-0.mol
• Article Data: 3

Chemical Properties

• Appearance: /
• Solubility: ≥18.47 mg/mL in DMSO; ≥2.14 mg/mL in EtOH; ≥29.65 mg/mL in H2O
• CAS DataBase Reference: LOXO-101 (sulfate)(CAS DataBase Reference)
• NIST Chemistry Reference: LOXO-101 (sulfate)(1223405-08-0)
• EPA Substance Registry System: LOXO-101 (sulfate)(1223405-08-0)

Safety Data

• Hazardous Substances Data: 1223405-08-0(Hazardous Substances Data)

Usage

Description

LOXO-101 (sulfate), also known as Larotrectinib Sulfate, is an orally bioavailable, potent, ATP-competitive inhibitor of tropomyosin receptor kinases (TRKA, TRKB, and TRKC). It exhibits low nanomolar range IC50 values for inhibiting all three TRK family members in binding and cellular assays, with a 100x selectivity over other kinases. LOXO-101 has demonstrated acceptable pharmaceutical properties and safety in nonclinical models. The TRK family of neurotrophin receptors and their ligands play a crucial role in regulating the growth, differentiation, and survival of neurons.

Uses

Used in Oncology:
LOXO-101 (sulfate) is used as a targeted therapy for the treatment of patients with solid tumors that harbor NTRK gene fusions without a known acquired resistance mutation. It has shown efficacy in inhibiting the TRK family of receptors, which are often involved in tumor growth and progression.
Used in Drug Development:
LOXO-101 (sulfate) serves as a valuable compound in the development of novel targeted therapies for various types of cancer. Its high selectivity and potent inhibition of TRK family members make it a promising candidate for further research and potential clinical applications in cancer treatment.
Used in Pharmaceutical Research:
As a potent and selective inhibitor of TRKA, TRKB, and TRKC, LOXO-101 (sulfate) is used in pharmaceutical research to study the role of these receptors in cancer and other diseases. It can also be employed to identify potential synergistic effects when combined with other targeted therapies or conventional chemotherapeutic drugs.
Used in Drug Delivery Systems:
Similar to gallotannin, LOXO-101 (sulfate) can be incorporated into drug delivery systems to enhance its bioavailability, delivery, and therapeutic outcomes. Various organic and metallic nanoparticles can be used as carriers for LOXO-101 (sulfate) delivery, aiming to improve its overall effectiveness in cancer treatment.

Solubility

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

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].

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.

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Relevant articles and documents

Assignment of NMR data and Conformational analysis of larotrectinib and its precursors

NMR experiments were used to identify the two main conformations of Larotrectinib and its synthetic precursor, the nitro compound 4. Conformational analysis by dynamic NMR was performed in different temperature and solvents, combining 2D EXSY and NOE expe

SUBSTITUTED PYRAZOLO[1,5-a]PYRIMIDINE COMPOUNDS AS TRK KINASE INHIBITORS

Compounds of Formula (I) in which R1, R2, R3, R4, X, Y and n have the meanings given in the specification, are inhibitors of Trk kinases and are useful in the treatment of diseases which can be treated with a Trk kinase inhibitor.