Lorlatinib (Synonyms: PF-06463922)

Name: Lorlatinib
Brand: MedChemExpress
SKU: HY-12215
Rating: 5.0 (31 reviews)

Cat. No.: HY-12215 Purity: 99.92%: FAQs
Data Sheet SDS COA Handling Instructions

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Lorlatinib (PF-06463922) is a selective, orally active, brain-penetrant and ATP-competitive ROS1/ALK inhibitor with anticancer activity. Lorlatinib has K_is of <0.025 nM, <0.07 nM, and 0.7 nM for ROS1, wild type ALK, and ALK^L1196M, respectively. Lorlatinib targets to EML4-ALK, and inhibits ALK phosphorylation with IC₅₀s of 15-43 nM (ALK^L1196), 14-80 nM (ALK^G1269A), 38-50 nM (ALK^1151Tins), 77-113 nM (ALK^G1202R), respectively.

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

Lorlatinib Chemical Structure

CAS No. : 1454846-35-5

Size	Price	Stock	Quantity
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO ready for reconstitution	USD 79	In-stock	Estimated Time of Arrival: December 31
Solution
10 mM * 1 mL in DMSO	USD 79	In-stock	Estimated Time of Arrival: December 31
Solid
5 mg	USD 72	In-stock	Estimated Time of Arrival: December 31
10 mg	USD 108	In-stock	Estimated Time of Arrival: December 31
25 mg	USD 180	In-stock	Estimated Time of Arrival: December 31
50 mg	USD 288	In-stock	Estimated Time of Arrival: December 31
100 mg	USD 504	In-stock	Estimated Time of Arrival: December 31
200 mg		Get quote
500 mg		Get quote

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Customer Review

Based on 31 publication(s) in Google Scholar

Other Forms of Lorlatinib:

Lorlatinib-13C,d3 Get quote
Deulorlatinib Get quote
Lorlatinib acetate Get quote
Lorlatinib (Standard) Get quote

30 Publications Citing Use of MCE Lorlatinib

Proliferation Assay

: Lorlatinib purchased from MedChemExpress. Usage Cited in: Nat Commun. 2017 Oct 30;8(1):1197. [Abstract]; Representative photographs (left) and quantification (right) of soft agar colony formation assay.

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Description

IC₅₀ & Target

IC50: 15-43 nM (ALK^L1196), 14-80 nM (ALK^G1269A), 38-50 nM (ALK^1151Tins), 77-113 nM (ALK^G1202R)^[3]
Ki: <0.07 nM (ALK^WT), 0.6 nM (ALK^L1996M), 0.9 nM (ALK^G1269A), 0.1 nM (ALK^1151Tins), <0.1 nM (ALK^L1152R), 0.2 nM (ALK^S1206Y), <0.1 nM (ALK^C1156Y), <0.1nM (ALK^F1174L)^[3]

Cellular Effect

Cell Line	Type	Value	Description	References
BaF3	IC₅₀	> 1000 nM Compound: 5	Antiproliferative activity against IL3-stimulated mouse BAF3 cells after 72 hrs by SRB or CCK8 assay Antiproliferative activity against IL3-stimulated mouse BAF3 cells after 72 hrs by SRB or CCK8 assay	[PMID: 29288940]
BaF3	IC₅₀	1.2 nM Compound: 5	Antiproliferative activity against mouse BAF3 cells harboring CD74-ROS1 after 72 hrs by SRB or CCK8 assay Antiproliferative activity against mouse BAF3 cells harboring CD74-ROS1 after 72 hrs by SRB or CCK8 assay	[PMID: 29288940]
BaF3	IC₅₀	2.9 nM Compound: 5	Antiproliferative activity against mouse BAF3 cells harboring EML4-ALK after 72 hrs by SRB or CCK8 assay Antiproliferative activity against mouse BAF3 cells harboring EML4-ALK after 72 hrs by SRB or CCK8 assay	[PMID: 29288940]
BaF3	IC₅₀	200 nM Compound: 5	Antiproliferative activity against mouse BAF3 cells harboring EML4-ALK G1202R mutant after 72 hrs by SRB or CCK8 assay Antiproliferative activity against mouse BAF3 cells harboring EML4-ALK G1202R mutant after 72 hrs by SRB or CCK8 assay	[PMID: 29288940]
BaF3	IC₅₀	262 nM Compound: 5	Antiproliferative activity against mouse BAF3 cells harboring CD74-ROS1 G2032R mutant after 72 hrs by SRB or CCK8 assay Antiproliferative activity against mouse BAF3 cells harboring CD74-ROS1 G2032R mutant after 72 hrs by SRB or CCK8 assay	[PMID: 29288940]
BaF3	IC₅₀	42.4 nM Compound: 5	Antiproliferative activity against mouse BAF3 cells harboring EML4-ALK L1196M mutant after 72 hrs by SRB or CCK8 assay Antiproliferative activity against mouse BAF3 cells harboring EML4-ALK L1196M mutant after 72 hrs by SRB or CCK8 assay	[PMID: 29288940]
HCC78	IC₅₀	357 nM Compound: 5	Antiproliferative activity against human HCC78 cells harboring SLC34A2-ROS1 after 72 hrs by SRB or CCK8 assay Antiproliferative activity against human HCC78 cells harboring SLC34A2-ROS1 after 72 hrs by SRB or CCK8 assay	[PMID: 29288940]
KARPAS-299	IC₅₀	3 nM Compound: 5	Antiproliferative activity against human KARPAS299 cells harboring NPM-ALK after 72 hrs by SRB or CCK8 assay Antiproliferative activity against human KARPAS299 cells harboring NPM-ALK after 72 hrs by SRB or CCK8 assay	[PMID: 29288940]
NCI-H3122	IC₅₀	7.8 nM Compound: 5	Antiproliferative activity against human NCI-H3122 cells after 72 hrs by SRB or CCK8 assay Antiproliferative activity against human NCI-H3122 cells after 72 hrs by SRB or CCK8 assay	[PMID: 29288940]
NIH3T3	IC₅₀	0.2 nM Compound: 8k, PF-06463922	Inhibition of human EML4-fused ALK F1174L mutant expressed in mouse NIH-3T3 cells assessed as phospho-ALK level after 1 hr by sandwich ELISA Inhibition of human EML4-fused ALK F1174L mutant expressed in mouse NIH-3T3 cells assessed as phospho-ALK level after 1 hr by sandwich ELISA	[PMID: 24819116]
NIH3T3	IC₅₀	1.3 nM Compound: 8k, PF-06463922	Inhibition of wild type human EML4-fused ALK expressed in mouse NIH-3T3 cells assessed as phosphorylated ALK level after 1 hr by sandwich ELISA Inhibition of wild type human EML4-fused ALK expressed in mouse NIH-3T3 cells assessed as phosphorylated ALK level after 1 hr by sandwich ELISA	[PMID: 24819116]
NIH3T3	IC₅₀	1.6 nM Compound: 8k, PF-06463922	Inhibition of human EML4-fused ALK C1156Y mutant expressed in mouse NIH-3T3 cells assessed as phospho-ALK level after 1 hr by sandwich ELISA Inhibition of human EML4-fused ALK C1156Y mutant expressed in mouse NIH-3T3 cells assessed as phospho-ALK level after 1 hr by sandwich ELISA	[PMID: 24819116]
NIH3T3	IC₅₀	15 nM Compound: 8k, PF-06463922	Inhibition of human EML4-fused ALK G1269A mutant expressed in mouse NIH-3T3 cells assessed as phospho-ALK level after 1 hr by sandwich ELISA Inhibition of human EML4-fused ALK G1269A mutant expressed in mouse NIH-3T3 cells assessed as phospho-ALK level after 1 hr by sandwich ELISA	[PMID: 24819116]
NIH3T3	IC₅₀	21 nM Compound: 8k, PF-06463922	Inhibition of human EML4-fused ALK L1196M mutant expressed in mouse NIH-3T3 cells assessed as phospho-ALK level after 1 hr by sandwich ELISA Inhibition of human EML4-fused ALK L1196M mutant expressed in mouse NIH-3T3 cells assessed as phospho-ALK level after 1 hr by sandwich ELISA	[PMID: 24819116]
NIH3T3	IC₅₀	38 nM Compound: 8k, PF-06463922	Inhibition of human EML4-fused ALK 1151Tins mutant expressed in mouse NIH-3T3 cells assessed as phospho-ALK level after 1 hr by sandwich ELISA Inhibition of human EML4-fused ALK 1151Tins mutant expressed in mouse NIH-3T3 cells assessed as phospho-ALK level after 1 hr by sandwich ELISA	[PMID: 24819116]
NIH3T3	IC₅₀	4.2 nM Compound: 8k, PF-06463922	Inhibition of human EML4-fused ALK S1206Y mutant expressed in mouse NIH-3T3 cells assessed as phospho-ALK level after 1 hr by sandwich ELISA Inhibition of human EML4-fused ALK S1206Y mutant expressed in mouse NIH-3T3 cells assessed as phospho-ALK level after 1 hr by sandwich ELISA	[PMID: 24819116]
NIH3T3	IC₅₀	77 nM Compound: 8k, PF-06463922	Inhibition of human EML4-fused ALK G1202R mutant expressed in mouse NIH-3T3 cells assessed as phospho-ALK level after 1 hr by sandwich ELISA Inhibition of human EML4-fused ALK G1202R mutant expressed in mouse NIH-3T3 cells assessed as phospho-ALK level after 1 hr by sandwich ELISA	[PMID: 24819116]
NIH3T3	IC₅₀	9 nM Compound: 8k, PF-06463922	Inhibition of human EML4-fused ALK L1152R mutant expressed in mouse NIH-3T3 cells assessed as phospho-ALK level after 1 hr by sandwich ELISA Inhibition of human EML4-fused ALK L1152R mutant expressed in mouse NIH-3T3 cells assessed as phospho-ALK level after 1 hr by sandwich ELISA	[PMID: 24819116]
SU-DHL-1	IC₅₀	4.9 nM Compound: 5	Antiproliferative activity against human SU-DHL1 cells harboring NPM-ALK after 72 hrs by SRB or CCK8 assay Antiproliferative activity against human SU-DHL1 cells harboring NPM-ALK after 72 hrs by SRB or CCK8 assay	[PMID: 29288940]

In Vitro

Lorlatinib (PF-06463922) demonstrates significant cell activity against ALK and a large set of ALK clinical mutations with IC₅₀ ranging from 0.2 nM-77 nM^[1]. Lorlatinib significantly inhibits cell proliferation and induces cell apoptosis in the HCC78 human NSCLC cells harboring SLC34A2-ROS1 fusions and the BaF3-CD74-ROS1 cells expressing human CD74-ROS1. Lorlatinib also shows potent growth inhibitory activity and induces apoptosis in the NSCLC cells harboring either non-mutant ALK or mutant ALK fusions^[2].

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

In Vivo

In rats, Lorlatinib (PF-06463922) displays low plasma clearance, a moderate volume of distribution, a reasonable half-life, low propensity for p-glycoprotein 1-mediated efflux and a bioavailability of 100%^[1]. In vivo, Lorlatinib shows cytoreductive antitumor efficacy in the NIH3T3 xenograft models expressing human CD74-ROS1 and Fig-ROS1 via inhibition in ROS1 phosphorylation and the downstream signaling molecules, as well as inhibition of the cell cycle protein Cyclin D1 in tumors. Lorlatinib also demonstrates marked antitumor activity in mice bearing tumor xenografts expressing EML4-ALK, EML4-ALK-L1196M, EML4-ALK-G1269A, EML4-ALK-G1202R or NPM-ALK^[2].

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

Clinical Trial

Molecular Weight

406.41

Formula

C₂₁H₁₉FN₆O₂

CAS No.

1454846-35-5

Appearance

Solid

Color

White to off-white

SMILES

CN1C(C#N)=C2C(CN(C)C(C3=C([C@@H](C)OC4=C(N)N=CC2=C4)C=C(F)C=C3)=O)=N1

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	2 years
	-20°C	1 year

Solvent & Solubility

In Vitro:

DMSO : ≥ 28 mg/mL (68.90 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	2.4606 mL	12.3028 mL	24.6057 mL
5 mM	0.4921 mL	2.4606 mL	4.9211 mL
10 mM	0.2461 mL	1.2303 mL	2.4606 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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Molarity Calculator
Dilution Calculator

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

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

This equation is commonly abbreviated as: C₁V₁ = C₂V₂

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Concentration _(final)

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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 (6.15 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 (6.15 mM); Suspended solution; Need ultrasonic

This protocol yields a suspended solution of 2.5 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.
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.
Protocol 3

Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 2.5 mg/mL (6.15 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.
Protocol 4

Add each solvent one by one: 5% DMSO 40% PEG300 5% Tween-80 50% Saline
Solubility: ≥ 2.5 mg/mL (6.15 mM); Clear solution

For the following dissolution methods, please prepare the working solution directly. It is recommended to prepare fresh solutions and use them promptly within a short period of time.
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: 50% PEG300 50% Saline
Solubility: 5 mg/mL (12.30 mM); Clear solution; Need ultrasonic
Protocol 2

Add each solvent one by one: 0.5% CMC/saline water
Solubility: 1 mg/mL (2.46 mM); Suspended solution; Need ultrasonic

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

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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: 99.92%

Select Batch:

Data Sheet (285 KB) SDS (393 KB)

COA (256 KB) HNMR (254 KB) LCMS (254 KB) Elemental Analysis Report (114 KB)

Handling Instructions (2659 KB)

References

[1]. Zou HY, et al. PF-06463922, an ALK/ROS1 Inhibitor, Overcomes Resistance to First and Second Generation ALK Inhibitors in Preclinical Models. Cancer Cell. 2015 Jul 13;28(1):70-81. [Content Brief]

[2]. Johnson TW, et al. Discovery of (10R)-7-amino-12-fluoro-2,10,16-trimethyl-15-oxo-10,15,16,17-tetrahydro-2H-8,4-(metheno)pyrazolo[4,3-h][2,5,11]-benzoxadiazacyclotetradecine-3-carbonitrile (PF-06463922), a macrocyclic inhibitor of anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) with preclinical brain exposure and broad-spectrum potency against ALK-resistant mutations. J Med Chem. 2014 Jun 12;57(11):4720-44. [Content Brief]

[3]. Zou HY, et al. PF-06463922 is a potent and selective next-generation ROS1/ALK inhibitor capable of blocking PF-02341066-resistant ROS1 mutations. Proc Natl Acad Sci U S A. 2015 Mar 17;112(11):3493-8 [Content Brief]

Cell Assay ^[2]	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 Lorlatinib 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. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration ^[2]	De novoGBM tumorigenesis is initiated in LSL-FIG-ROS1;Cdkn2a−/−;LSL-Luc mice through intracranial stereotactic injections of Adeno-Cre as described previously. Tumor development is monitored using BLI as described below. Once tumors reach a given size (10⁷ p^-1·s^-1·cm^-2·sr^-1), animals are randomLy enrolled into vehicle control or 3-, 7-, or 14-d treatment with the indicated doses of Lorlatinib. Drug is administered through s.c. implanted Alzet osmotic pumps. After treatment, mice are killed, GBM tumors are microdissected, and tissues are flash-frozen in liquid N₂. The remaining brains are processed for histology. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
References	[1]. Zou HY, et al. PF-06463922, an ALK/ROS1 Inhibitor, Overcomes Resistance to First and Second Generation ALK Inhibitors in Preclinical Models. Cancer Cell. 2015 Jul 13;28(1):70-81. [Content Brief] [2]. Johnson TW, et al. Discovery of (10R)-7-amino-12-fluoro-2,10,16-trimethyl-15-oxo-10,15,16,17-tetrahydro-2H-8,4-(metheno)pyrazolo[4,3-h][2,5,11]-benzoxadiazacyclotetradecine-3-carbonitrile (PF-06463922), a macrocyclic inhibitor of anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) with preclinical brain exposure and broad-spectrum potency against ALK-resistant mutations. J Med Chem. 2014 Jun 12;57(11):4720-44. [Content Brief] [3]. Zou HY, et al. PF-06463922 is a potent and selective next-generation ROS1/ALK inhibitor capable of blocking PF-02341066-resistant ROS1 mutations. Proc Natl Acad Sci U S A. 2015 Mar 17;112(11):3493-8 [Content Brief]

Complete Stock Solution Preparation Table

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg

DMSO	1 mM	2.4606 mL	12.3028 mL	24.6057 mL	61.5142 mL
	5 mM	0.4921 mL	2.4606 mL	4.9211 mL	12.3028 mL
	10 mM	0.2461 mL	1.2303 mL	2.4606 mL	6.1514 mL
	15 mM	0.1640 mL	0.8202 mL	1.6404 mL	4.1009 mL
	20 mM	0.1230 mL	0.6151 mL	1.2303 mL	3.0757 mL
	25 mM	0.0984 mL	0.4921 mL	0.9842 mL	2.4606 mL
	30 mM	0.0820 mL	0.4101 mL	0.8202 mL	2.0505 mL
	40 mM	0.0615 mL	0.3076 mL	0.6151 mL	1.5379 mL
	50 mM	0.0492 mL	0.2461 mL	0.4921 mL	1.2303 mL
	60 mM	0.0410 mL	0.2050 mL	0.4101 mL	1.0252 mL

Lorlatinib Related Classifications

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Lorlatinib (Synonyms: PF-06463922)

Customer Review

Other Forms of Lorlatinib:

30 Publications Citing Use of MCE Lorlatinib

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Lorlatinib (Synonyms: PF-06463922)

Customer Review

Other Forms of Lorlatinib:

Lorlatinib Related Antibodies

30 Publications Citing Use of MCE Lorlatinib

Featured Recommendations

•Related Screening Libraries:

•Related Small Molecules:

•Related Proteins:

Biological Activity

Protocol

Purity & Documentation

References

Customer Review

Lorlatinib Related Antibodies

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Dilution Calculator

Complete Stock Solution Preparation Table

Lorlatinib Related Classifications

Keywords:

Your Recently Viewed Products:

Customer Review

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