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LOXO-101 (Larotrectinib) sulfate

Catalog No.GC15282

LOXO-101 (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).

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LOXO-101 (Larotrectinib) sulfate Chemical Structure

Cas No.: 1223405-08-0

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5mg
$39.00
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25mg
$98.00
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100mg
$288.00
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500mg
$917.00
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1g
$1,648.00
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Sample solution is provided at 25 µL, 10mM.

Product Documents

Quality Control & SDS

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Protocol

Animal experiment:

Mice[4]Athymic nude mice are used throughout the study. 5×105 KM12 cells are injected subcutaneously into the dorsal flank area of the mice. Tumor volume is monitored by direct measurement with calipers and calculated by the formula: length × (width2)/2. Following the establishment of tumor and when the tumor size is between 150-200 mm2, mice are randomly selected to receive diluent, 60 mg/kg/dose or 200 mg/kg/dose of Larotrectinib (LOXO-101). Larotrectinib (LOXO-101) is administered by oral gavage once daily for 14 days. After the last dose, tissue and blood are collected at 3, 6 and 24 hours post-treatment[4].

References:

[1]. Karyn Bouhana, et al. LOXO-101, a pan TRK inhibitor, For The Treatment Of TRK-driven Cancers.
[2]. 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.
[3]. Nagasubramanian R, et al. Infantile Fibrosarcoma With NTRK3-ETV6 Fusion Successfully Treated With the Tropomyosin-Related Kinase Inhibitor LOXO-101. Pediatr Blood Cancer. 2016 Aug;63(8):1468-70.
[4]. 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.
[5]. Kathryn G, et al. Genetic Modeling and Therapeutic Targeting of ETV6-NTRK3 with Loxo-101in Acute Lymphoblastic Leukemia. Blood 2016 128:278.

Background

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 [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].

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 [1].

Reference:
[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.

Chemical Properties

Cas No. 1223405-08-0 SDF
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[C@@H](O)CC1)NC2=C3N=C(N4[C@@H](C5=CC(F)=CC=C5F)CCC4)C=CN3N=C2
Formula C21H24F2N6O6S M.Wt 526.51
Solubility DMSO : 100mg/mL Storage Store at -20°C
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

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1 mg 5 mg 10 mg
1 mM 1.8993 mL 9.4965 mL 18.993 mL
5 mM 0.3799 mL 1.8993 mL 3.7986 mL
10 mM 0.1899 mL 0.9496 mL 1.8993 mL
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Average Rating: 5 ★★★★★ (Based on Reviews and 27 reference(s) in Google Scholar.)

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