Home Protein Tyrosine Kinase ALK inhibitor - ROS1 inhibitor - Apoptosis related activator Lorlatinib (PF-6463922) For research use only.

Lorlatinib (PF-6463922)

Lorlatinib (PF-6463922) is a potent, dual ALK/ROS1 inhibitor with Ki of <0.02 nM, <0.07 nM, and 0.7 nM for ROS1, ALK (WT), and ALK (L1196M), respectively. PF-06463922 induces apoptosis. Phase 1.

Lorlatinib (PF-6463922) Chemical Structure

Lorlatinib (PF-6463922) Chemical Structure

CAS: 1454846-35-5

Selleck's Lorlatinib (PF-6463922) has been cited by 62 publications

Purity & Quality Control

Batch: Purity: 99.95%
99.95

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Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
NIH-3T3 Function assay 1 hr 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, IC50 = 0.0002 μM. 24819116
NIH/3T3 Function assay Inhibition of wild type EML4/ALK F1174L mutant (unknown origin) expressed in NIH/3T3 cells, IC50 = 0.0002 μM. 28431340
BAF3 Antiproliferative assay 72 hrs Antiproliferative activity against mouse BAF3 cells harboring CD74-ROS1 after 72 hrs by SRB or CCK8 assay, IC50 = 0.0012 μM. 29288940
NIH-3T3 Function assay 1 hr 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, IC50 = 0.0013 μM. 24819116
NIH/3T3 Function assay Inhibition of wild type EML4/ALK (unknown origin) expressed in NIH/3T3 cells, IC50 = 0.0013 μM. 28431340
NIH-3T3 Function assay 1 hr 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, IC50 = 0.0016 μM. 24819116
NIH/3T3 Function assay Inhibition of wild type EML4/ALK C1156Y mutant (unknown origin) expressed in NIH/3T3 cells, IC50 = 0.0016 μM. 28431340
BAF3 Antiproliferative assay 72 hrs Antiproliferative activity against mouse BAF3 cells harboring EML4-ALK after 72 hrs by SRB or CCK8 assay, IC50 = 0.0029 μM. 29288940
KARPAS299 Antiproliferative assay 72 hrs Antiproliferative activity against human KARPAS299 cells harboring NPM-ALK after 72 hrs by SRB or CCK8 assay, IC50 = 0.003 μM. 29288940
NIH-3T3 Function assay 1 hr 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, IC50 = 0.0042 μM. 24819116
NIH/3T3 Function assay Inhibition of wild type EML4/ALK S1206Y mutant (unknown origin) expressed in NIH/3T3 cells, IC50 = 0.0042 μM. 28431340
SU-DHL1 Antiproliferative assay 72 hrs Antiproliferative activity against human SU-DHL1 cells harboring NPM-ALK after 72 hrs by SRB or CCK8 assay, IC50 = 0.0049 μM. 29288940
NCI-H3122 Antiproliferative assay 72 hrs Antiproliferative activity against human NCI-H3122 cells after 72 hrs by SRB or CCK8 assay, IC50 = 0.0078 μM. 29288940
NIH-3T3 Function assay 1 hr 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, IC50 = 0.009 μM. 24819116
NIH/3T3 Function assay Inhibition of wild type EML4/ALK L1152R mutant (unknown origin) expressed in NIH/3T3 cells, IC50 = 0.009 μM. 28431340
NIH-3T3 Function assay 1 hr 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, IC50 = 0.015 μM. 24819116
NIH/3T3 Function assay Inhibition of wild type EML4/ALK G1269A mutant (unknown origin) expressed in NIH/3T3 cells, IC50 = 0.015 μM. 28431340
NIH-3T3 Function assay 1 hr 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, IC50 = 0.021 μM. 24819116
NIH/3T3 Function assay Inhibition of wild type EML4/ALK L1196M mutant (unknown origin) expressed in NIH/3T3 cells, IC50 = 0.021 μM. 28431340
NIH-3T3 Function assay 1 hr 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, IC50 = 0.038 μM. 24819116
NIH/3T3 Function assay Inhibition of wild type EML4/ALK 1151Tins mutant (unknown origin) expressed in NIH/3T3 cells, IC50 = 0.038 μM. 28431340
BAF3 Antiproliferative assay 72 hrs Antiproliferative activity against mouse BAF3 cells harboring EML4-ALK L1196M mutant after 72 hrs by SRB or CCK8 assay, IC50 = 0.0424 μM. 29288940
NIH-3T3 Function assay 1 hr 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, IC50 = 0.077 μM. 24819116
NIH/3T3 Function assay Inhibition of wild type EML4/ALK G1202R mutant (unknown origin) expressed in NIH/3T3 cells, IC50 = 0.077 μM. 28431340
BAF3 Antiproliferative assay 72 hrs Antiproliferative activity against mouse BAF3 cells harboring EML4-ALK G1202R mutant after 72 hrs by SRB or CCK8 assay, IC50 = 0.2 μM. 29288940
BAF3 Antiproliferative assay 72 hrs Antiproliferative activity against mouse BAF3 cells harboring CD74-ROS1 G2032R mutant after 72 hrs by SRB or CCK8 assay, IC50 = 0.262 μM. 29288940
HCC78 Antiproliferative assay 72 hrs Antiproliferative activity against human HCC78 cells harboring SLC34A2-ROS1 after 72 hrs by SRB or CCK8 assay, IC50 = 0.357 μM. 29288940
SU-DHL1 Function assay Inhibition of ALK in human SU-DHL1 cells assessed as reduction in STAT3 phosphorylation at Y705 residue at 20 to 80 nM after 1 hr by Western blot analysis 29288940
SU-DHL1 Function assay Inhibition of ALK in human SU-DHL1 cells assessed as reduction in Akt phosphorylation at S473 residue at 20 to 80 nM after 1 hr by Western blot analysis 29288940
SU-DHL1 Function assay Inhibition of ALK phosphorylation at Y1278 residue in human SU-DHL1 cells at 20 to 80 nM after 1 hr by Western blot analysis 29288940
SU-DHL1 Function assay Inhibition of ALK in human SU-DHL1 cells assessed as reduction in ERK phosphorylation at T202//Y204 residues at 20 to 80 nM after 1 hr by Western blot analysis 29288940
NCI-H3122 Function assay Inhibition of ALK phosphorylation at Y1278 residue in human NCI-H3122 cells at 20 to 80 nM after 1 hr by Western blot analysis 29288940
NCI-H3122 Function assay Inhibition of ALK in human NCI-H3122 cells assessed as reduction in STAT3 phosphorylation at Y705 residue at 20 to 80 nM after 1 hr by Western blot analysis 29288940
NCI-H3122 Function assay Inhibition of ALK in human NCI-H3122 cells assessed as reduction in Akt phosphorylation at S473 residue at 20 to 80 nM after 1 hr by Western blot analysis 29288940
NCI-H3122 Function assay Inhibition of ALK in human NCI-H3122 cells assessed as reduction in ERK phosphorylation at T202//Y204 residues at 20 to 80 nM after 1 hr by Western blot analysis 29288940
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Biological Activity

Description Lorlatinib (PF-6463922) is a potent, dual ALK/ROS1 inhibitor with Ki of <0.02 nM, <0.07 nM, and 0.7 nM for ROS1, ALK (WT), and ALK (L1196M), respectively. PF-06463922 induces apoptosis. Phase 1.
Targets
ROS1 [1]
(Cell-free assay)		 ALK [1]
(Cell-free assay)		 ALK (L1196M) [1]
(Cell-free assay)		 LTK (TYK1) [1]
(Cell-free assay)		 FER [1]
(Cell-free assay)		 Click to View More Targets
<0.02 nM(Ki) <0.07 nM(Ki) 0.07 nM(Ki) 2.7 nM 3.3 nM
In vitro
In vitro 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] PF-06463922 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.[2] PF-06463922 also shows potent growth inhibitory activity and induces apoptosis in the NSCLC cells harboring either non-mutant ALK or mutant ALK fusions. [3]
Experimental Result Images Methods Biomarkers Images PMID
Western blot p-ALK / ALK 29650534
In Vivo
In vivo In rats, 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, PF-06463922 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. [2] In vivo, PF-06463922 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. [3]
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT06092086 Recruiting ALK Positive Non-small Cell Lung Cancer Guangdong Association of Clinical Trials August 18 2023 Phase 2
NCT05297890 Active not recruiting Advanced or Metastatic ROS1-Positive Non-Small Cell Lung Cancer CStone Pharmaceuticals|Pfizer May 27 2022 Phase 2
NCT05224609 Recruiting Moderate Hepatic Impairment|Severe Hepatic Impairment|Healthy Volunteers Pfizer April 28 2022 Phase 1
NCT04979988 Completed ALK-positive Non-small-cell Lung Cancer Pfizer August 2 2021 --
NCT03726333 Terminated Advanced Cancers Pfizer January 14 2020 Phase 1

Chemical lnformation & Solubility

Molecular Weight 406.41 Formula

C21H19FN6O2
CAS No. 1454846-35-5 SDF Download Lorlatinib (PF-6463922) SDF
Smiles CC1C2=C(C=CC(=C2)F)C(=O)N(CC3=NN(C(=C3C4=CC(=C(N=C4)N)O1)C#N)C)C
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 81 mg/mL ( (199.3 mM)； Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 40.5 mg/mL

Water : Insoluble


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Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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Do you have any special suggestions for solution of S7536, Lorlatinib (PF-6463922) to be applied to mouse models?

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For S7536, we recommend 2% DMSO+30% PEG 300+ddH2O (up to 5mg/ml) for in vivo application.

ALK Signaling Pathway Map

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