2. Neuronal Signaling Protein Tyrosine Kinase/RTK Apoptosis
  3. Trk Receptor Apoptosis
  4. Larotrectinib

Larotrectinib  (Synonyms: LOXO-101; ARRY-470)

Cat. No.: HY-12866 Purity: 99.95%
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Larotrectinib (LOXO-101) 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).

For research use only. We do not sell to patients.

Larotrectinib Chemical Structure

Larotrectinib Chemical Structure

CAS No. : 1223403-58-4

Size Price Stock Quantity
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO
ready for reconstitution
 USD 101 In-stock
Solution
10 mM * 1 mL in DMSO USD 101 In-stock
Solid
1 mg USD 37 In-stock
5 mg USD 92 In-stock
10 mg USD 120 In-stock
50 mg USD 320 In-stock
100 mg USD 480 In-stock
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Based on 9 publication(s) in Google Scholar

Other Forms of Larotrectinib:

Larotrectinib Related Antibodies

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View All Trk Receptor Isoform Specific Products:

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TrkA TrkB TrkC Trk

  • Biological Activity

  • Protocol

  • Purity & Documentation

  • References

  • Customer Review

Description

Larotrectinib (LOXO-101) 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).

IC50 & Target[1][2]

TrkA

 

TrkB

 

TrkC

 

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[1][2]. 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[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Larotrectinib Related Antibodies
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%[1]. Athymic nude mice injected with KM12 cells are treated with Larotrectinib (LOXO-101) orally daily for 2 weeks. Dose-dependent tumor inhibition is observed demonstrating the ability of this selective compound to inhibit tumor growth in vivo[4]. 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 (LOXO-101) are still alive and leukemia-free four weeks after the cessation of treatment, as determined by Xenogen imaging[5].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
Molecular Weight

428.44

Formula

C21H22F2N6O2
CAS No.
Appearance

Solid

Color

White to yellow

SMILES

O=C(N1C[C@@H](O)CC1)NC2=C3N=C(N4[C@@H](C5=CC(F)=CC=C5F)CCC4)C=CN3N=C2
Shipping

Room temperature in continental US; may vary elsewhere.
Storage
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 1 year
-20°C 6 months
Solvent & Solubility
In Vitro: 

DMSO : ≥ 4.6 mg/mL (10.74 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

*"≥" means soluble, but saturation unknown.

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 2.3340 mL 11.6702 mL 23.3405 mL
5 mM 0.4668 mL 2.3340 mL 4.6681 mL
View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.

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Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass
=
Concentration
×
Volume
×
Molecular Weight *

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start)

C1

×
Volume (start)

V1

=
Concentration (final)

C2

×
Volume (final)

V2

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

  • Protocol 1

    Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% Saline

    Solubility: ≥ 2.5 mg/mL (5.84 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

    Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
  • Protocol 2

    Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in Saline)

    Solubility: ≥ 2.5 mg/mL (5.84 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

    Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

g

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO +
% 
+
%
Tween-80 +
%
Saline
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Calculation results:
Working solution concentration: mg/mL
Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
 If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Purity & Documentation

Purity: 99.95%

COA (254 KB) LCMS (94 KB)

Handling Instructions (2659 KB)
References
Animal Administration
[4]

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].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.
References

Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 2.3340 mL 11.6702 mL 23.3405 mL 58.3512 mL
5 mM 0.4668 mL 2.3340 mL 4.6681 mL 11.6702 mL
10 mM 0.2334 mL 1.1670 mL 2.3340 mL 5.8351 mL
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Larotrectinib Related Classifications

Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

Larotrectinib1223403-58-4LOXO-101 ARRY-470LOXO101LOXO 101ARRY470ARRY 470ARRY-470Trk ReceptorApoptosisTropomyosin related kinase receptor Inhibitorinhibitorinhibit

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