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Selitrectinib (LOXO-195) Trk receptor inhibitor

Name: Selitrectinib (LOXO-195)
Brand: Selleck Chemicals
SKU: S8636
Rating: 5 (4 reviews)

Cat.No.S8636

Selitrectinib (LOXO-195, BAY 2731954) is an orally available, highly potent, and selective TRK kinase inhibitor with low nanomolar inhibitory activity against TRKA G595R, TRKC G623R, and TRKA G667C, IC50s ranging from 2.0 to 9.8 nmol/L. This compound is more than 1,000-fold selective for 98% of non-TRK kinases tested.

Chemical Structure

Molecular Weight: 380.42

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Quality Control

Batch: Purity: 99.92%

99.92

Related Targets	EGFR VEGFR PDGFR FGFR c-Met Src MEK CSF-1R FLT3 HER2
Other Trk receptor Inhibitors	ANA-12 GW441756 7,8-Dihydroxyflavone GNF-5837 Altiratinib LM22B-10 N-Acetyl-5-hydroxytryptamine PF-06273340 CH7057288 LM22A-4

Chemical Information, Storage & Stability

Molecular Weight	380.42	Formula	C₂₀H₂₁FN₆O	Storage (From the date of receipt)	3 years -20°C powder
CAS No.	2097002-61-2	--		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	BAY 2731954			Smiles	CC1CCC2=C(C=C(C=N2)F)C3CCCN3C4=NC5=C(C=NN5C=C4)C(=O)N1

Solubility

In vitro
Batch:

DMSO : 38 mg/mL (99.88 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 15 mg/mL

Water : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
=	×	×

Dilution Calculator Molecular Weight Calculator

In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	2.000mg/ml (5.26mM)	Taking the 1 mL working solution as an example, add 50 μL of 40 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to make it clear; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.

Mechanism of Action

Targets/IC₅₀/Ki	WT TRKA (Celll-free assay) 0.6 nM TRKA G595R (Cell-free assay) 2 nM TRKC G623R (Cell-free assay) 2.3 nM WT TRKC (Cell-free assay) 2.5 nM TRKC G696A (Cell-free assay) 2.5 nM TRKA G667C (Cell-free assay) 9.8 nM
In vitro	Selitrectinib (LOXO-195) potently inhibits diverse activated TRK kinases in vitro. At a concentration of 1 μM, which is approximately 1,667-fold higher than its IC50 for TRKA (0.6 nmol/L), this compound is more than 1,000-fold selective for 98% of non-TRK kinases tested (228 individual kinases). It demonstrates potent inhibition of cell proliferation in TRK fusion–containing KM12, CUTO-3, and MO-91 cell lines (IC50 ≤ 5 nmol/L). In contrast, treatment with concentrations up to 10 μmol/L has no inhibitory effect on the growth of the 84 cell lines that did not contain a TRK fusion.
In vivo	Selitrectinib (LOXO-195) is effective at reducing phosphorylated TRKA in tumours driven by ΔTRKA. It also causes inhibition of tumour growth relative to vehicle at all doses in four TRKA-dependent tumour models (NIH 3T3 ΔTRKA, ΔTRKA G595R, ΔTRKA G667C, and TPM3-NTRK1 fusion-positive KM12 colorectal cancer cells).
References	[1] https://pubmed.ncbi.nlm.nih.gov/28578312/ [2] https://pubmed.ncbi.nlm.nih.gov/31871300/ [3] https://pubmed.ncbi.nlm.nih.gov/33785654/

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT04275960	Completed	Solid Tumors Harboring NTRK Fusion	Bayer	February 28 2020	Phase 1
NCT03215511	Completed	Solid Tumors Harboring NTRK Fusion	Bayer	July 3 2017	Phase 1

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