Home Tools

Lorlatinib

Catalog No. T3061 CAS 1454846-35-5

Synonyms: PF-6463922, PF-06463922, Loratinib

Lorlatinib (PF-6463922) is an orally available, ATP-competitive inhibitor of the receptor tyrosine kinases, anaplastic lymphoma kinase (ALK) and C-ros oncogene 1 (Ros1), with potential antineoplastic activity.

All products from TargetMol are for Research Use Only. Not for Human or Veterinary or Therapeutic Use.

Lorlatinib, CAS 1454846-35-5

Pack Size	Availability	Price/USD
2 mg	In stock	$ 35.00
5 mg	In stock	$ 57.00
10 mg	In stock	$ 87.00
25 mg	In stock	$ 147.00
50 mg	In stock	$ 237.00
100 mg	In stock	$ 417.00
1 g	In stock	$ 945.00
1 mL * 10 mM (in DMSO)	In stock	$ 63.00

Bulk Inquiry

Select Batch

Purity: 99.93%

Purity: 99.82%

Biological Description

Chemical Properties

Storage & Solubility Information

Description	Lorlatinib (PF-6463922) is an orally available, ATP-competitive inhibitor of the receptor tyrosine kinases, anaplastic lymphoma kinase (ALK) and C-ros oncogene 1 (Ros1), with potential antineoplastic activity.
Targets&IC50	ROS1:<0.02 nM(Ki), ALK:<0.07 nM(Ki), TYK1/LTK:2.7 nM, ALK (L1196M):0.07 nM(Ki), FER:3.3 nM
In vitro	In NIH3T3 xenograft models expressing human CD74-ROS1 and Fig-ROS1, PF-06463922 inhibits cell proliferation by repressing ROS1 phosphorylation and downstream signaling molecules, including Cyclin D1. Furthermore, PF-06463922 demonstrates significant antitumor activity in mice bearing tumor grafts that overexpress EML4-ALK, EML4-ALK-L1196M, EML4-ALK-G1269A, EML4-ALK-G1202R, or NPM-ALK.
In vivo	PF-06463922 effectively inhibits cell proliferation and induces apoptosis in HCC78 human NSCLC cells containing SLC34A2-ROS1 fusions and in BaF3-CD74-ROS1 cells expressing human CD74-ROS1. It also demonstrates this inhibitory action on cell proliferation and induces apoptosis in NSCLC cells with either non-mutated or mutated ALK fusions. PF-06463922 exhibits significant cellular activity against ALK and a wide range of ALK clinical mutations (IC50=0.2-77 nM).
Kinase Assay	Recombinant human wild-type and mutant ALK kinase domain proteins (amino acids 1093–1411) are produced in-house using baculoviral expression, preactivated via autophosphorylation with MgATP, and assayed for kinase activity using a microfluidic mobility shift assay. The reactions contained 1.3 nM wild-type ALK or 0.5 nM mutant ALK (appropriate to produce 15-20% phosphorylation of peptide substrate after 1 h of reaction), 3 μM 5-FAM-KKSRGDYMTMQIG-CONH2), 5 mM MgCl2, and the Km level of ATP in 25 mM Hepes, pH 7.1. The inhibitors are shown to be ATP-competitive from kinetic and crystallographic studies. The Ki values are calculated by fitting the conversion (%) to a competitive inhibition equation. ROS1 enzyme is assayed as described above for ALK, except using 0.25 nM recombinant human ROS1 catalytic domain (amino acids 1883-2347). Kinase inhibitor selectivity is evaluated using a 206-kinase panel.
Cell Research	Cells are seeded in 96-well plates in growth medium containing 10% FBS and are cultured overnight at 37°C. The following day, serial dilutions of PF-06463922 or appropriate controls are added to the designated wells, and cells are incubated at 37°C for 72 h. A CellTiter-Glo assay is performed to determine the relative cell numbers. IC50 values are calculated by concentration-response curve fitting using a four-parameter analytical method.

Synonyms	PF-6463922, PF-06463922, Loratinib
Molecular Weight	406.41
Formula	C21H19FN6O2
CAS No.	1454846-35-5

Storage

Powder: -20°C for 3 years | In solvent: -80°C for 1 year

Solubility Information

Ethanol: 40.6 mg/mL (100 mM)

DMSO: 40.6 mg/mL (100 mM)

References and Literature

1. Johnson TW, et al. J Med Chem. 2014, 57(11), 4720-4744. 2. Zou HY, et al. Mol Cancer Ther. 2013, 12, A277. 3. Zou HY, et al. Mol Cancer Ther. 2013, 12, C253. 4. Sparidans R W, Li W, Schinkel A H, et al. Bioanalytical liquid chromatography-tandem mass spectrometric assay for the quantification of the ALK inhibitors alectinib, brigatinib and lorlatinib in plasma and mouse tissue homogenates[J]. Journal of pharmaceutical and biomedical analysis. 2018 Nov 30;161:136-143. 5. Spatari, Claudia, et al. Bioanalytical assay for the quantification of the ALK inhibitor lorlatinib in mouse plasma using liquid chromatography-tandem mass spectrometry. Journal of Chromatography B. 2018 Apr 15;1083:204-208. 6. Wenlong Li, Rolf W. Sparidans, Yaogeng Wang, Maria C. Lebre, Jos H. Beijnen, and Alfred H. Schinkel. Oral coadministration of elacridar and ritonavir enhances brain accumulation and oral availability of the novel ALK/ROS1 inhibitor lorlatinib [J]. European Journal of Pharmaceutics and Biopharmaceutics. 2019 Mar;136:120-130. 7. Wenlong Li, Rolf W. Sparidans, Yaogeng Wang, Maria C. Lebre, Els Wagenaar, Jos H. Beijnen, and Alfred H. P-glycoprotein (MDR1/ABCB1) restricts brain accumulation and Cytochrome P450-3A (CYP3A) limits oral availability of the novel ALK/ROS1 inhibitor lorlatinib [J]. International journal of cancer. 2018 Oct 15;143(8):2029-2038.

Citations

1. Li W, Sparidans R W, Wang Y, et al. P-glycoprotein (MDR1/ABCB1) restricts brain accumulation and Cytochrome P450-3A (CYP3A) limits oral availability of the novel ALK/ROS1 inhibitor lorlatinib. International Journal of Cancer. 2018, 143(8): 2029-2038 2. Li W, Sparidans R W, Wang Y, et al. Oral coadministration of elacridar and ritonavir enhances brain accumulation and oral availability of the novel ALK/ROS1 inhibitor lorlatinib. European Journal of Pharmaceutics and Biopharmaceutics. 2019, 136: 120-130 3. Spatari C, Li W, Schinkel A H, et al. Bioanalytical assay for the quantification of the ALK inhibitor lorlatinib in mouse plasma using liquid chromatography-tandem mass spectrometry. Journal of Chromatography B. 2018, 1083: 204-208 4. Sparidans R W, Li W, Schinkel A H, et al. Bioanalytical liquid chromatography-tandem mass spectrometric assay for the quantification of the ALK inhibitors alectinib, brigatinib and lorlatinib in plasma and mouse tissue homogenates. Journal of Pharmaceutical and Biomedical Analysis. 2018 Nov 30;161:136-143 5. Guan J, Borenäs M, Xiong J, et al.IGF1R Contributes to Cell Proliferation in ALK-Mutated Neuroblastoma with Preference for Activating the PI3K-AKT Signaling Pathway.Cancers.2023, 15(17): 4252.

Related compound libraries

This product is contained In the following compound libraries：

Tyrosine Kinase Inhibitor Library Anti-Cancer Clinical Compound Library Membrane Protein-targeted Compound Library Kinase Inhibitor Library Anti-Cancer Active Compound Library Anti-Cancer Approved Drug Library Inhibitor Library Drug Repurposing Compound Library FDA-Approved Kinase Inhibitor Library Anti-Cancer Drug Library

Related Products

Related compounds with same targets

Crizotinib Uniconazole Repotrectinib APG-2449 Taletrectinib Salvigenin ROS kinases-IN-1 ROS kinases-IN-2

Dose Conversion

You can also refer to dose conversion for different animals. More

In vivo Formulation Calculator (Clear solution)

Step One: Enter information below

Dosage

mg/kg

Average weight of animals

Dosing volume per animal

Number of animals

Step Two: Enter the in vivo formulation

% DMSO+

% +

% Tween 80+

% ddH₂O

%DMSO+

Calculate Reset

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 add μL PEG300， mix and clarify, next add μL Tween 80，mix and clarify, next add μL ddH₂O, mix and clarify.

Note:

Be sure to add the solvent(s) in order. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.

Calculator

Molarity Calculator

Dilution Calculator

Reconstitution Calculation

Molecular Weight Calculator

Mass

Concentration

Volume

Molecular Weight

Molarity Calculator allows you to calculate the

Mass of a compound required to prepare a solution of known volume and concentration
Volume of solution required to dissolve a compound of known mass to a desired concentration
Concentration of a solution resulting from a known mass of compound in a specific volume

See Example

An example of a molarity calculation using the molarity calculator
What is the mass of compound required to make a 10 mM stock solution in 10 ml of water given that the molecular weight of the compound is 197.13 g/mol?
Enter 197.13 into the Molecular Weight (MW) box
Enter 10 into the Concentration box and select the correct unit (millimolar)
Enter 10 into the Volume box and select the correct unit (milliliter)
Press calculate
The answer of 19.713 mg appears in the Mass box

Concentration (Start)

Volume (Start)

Concentration (End)

Volume (End)

Calculator the dilution required to prepare a stock solution

Calculate the dilution required to prepare a stock solution
The dilution calculator is a useful tool which allows you to calculate how to dilute a stock solution of known concentration. Enter C1, C2 & V2 to calculate V1.

See Example

An example of a dilution calculation using the Tocris dilution calculator
What volume of a given 10 mM stock solution is required to make 20ml of a 50 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=50 μM, V2=20 ml and V1 is the unknown:
Enter 10 into the Concentration (start) box and select the correct unit (millimolar)
Enter 50 into the Concentration (final) box and select the correct unit (micromolar)
Enter 20 into the Volume (final) box and select the correct unit (milliliter)
Press calculate
The answer of 100 microliter (0.1 ml) appears in the Volume (start) box

Volume (to add to vial)

Mass (in vial)

Desired Reconstitution Concentration

Calculate the volume of solvent required to reconstitute your vial.

The reconstitution calculator allows you to quickly calculate the volume of a reagent to reconstitute your vial.
Simply enter the mass of reagent and the target concentration and the calculator will determine the rest.

Molecule Formula

Molecular Weight g/mol

Enter the chemical formula of a compound to calculate its molar mass and elemental composition

Tip: Chemical formula is case sensitive: C10H16N2O2 c10h16n2o2

Instructions to calculate molar mass (molecular weight) of a chemical compound:
To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.
Definitions of molecular mass, molecular weight, molar mass and molar weight:
Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed n the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

bottom

Tech Support

Please see Inhibitor Handling Instructions for more frequently ask questions. Topics include: how to prepare stock solutions, how to store products, and cautions on cell-based assays & animal experiments, etc.

Keywords

Lorlatinib 1454846-35-5 Angiogenesis Apoptosis Immunology/Inflammation Tyrosine Kinase/Adaptors ROS Tyrosine Kinases ALK ROS Kinase ALK tyrosine kinase receptor Anaplastic lymphoma kinase PF 06463922 tyrosine inhibit Neuroblastoma Carcinoma Anaplastic lymphoma kinase (ALK) NSCLC Inhibitor PF06463922 mutation PF 6463922 PF-6463922 kinase Cluster of differentiation 246 brain-penetrant CD246 PF-06463922 third-generation PF6463922 Loratinib inhibitor

Products are chemical reagents for research use only and are not intended for human use. We do not sell to patients.