DGIdb - LORLATINIB Drug Record

LORLATINIB chembl:CHEMBL3286830 ApprovedAntineoplastic

Alternate Names:

LORBRENA
LORLATINIB
PF-06463922
PF-6463922
chemidplus:1454846-35-5
pubchem.compound:71731823
drugbank:12130
chembl:CHEMBL3286830

Drug Info:

Drug Categories	ugt1a3 substrates
Drug Categories	protein kinase inhibitors
Drug Categories	lactams
Drug Categories	kinase inhibitor
Drug Categories	cytochrome p-450 substrates
Drug Categories	cytochrome p-450 enzyme inhibitors
Drug Categories	cytochrome p-450 enzyme inducers
Drug Categories	cytochrome p-450 cyp3a5 substrates
Drug Categories	cytochrome p-450 cyp3a4 inducers
Drug Categories	cytochrome p-450 cyp3a substrates
Drug Categories	cytochrome p-450 cyp3a inhibitors
Drug Categories	cytochrome p-450 cyp3a inducers
Drug Categories	cytochrome p-450 cyp2c8 substrates
Drug Categories	cytochrome p-450 cyp2c19 substrates
Drug Categories	cytochrome p-450 cyp2b6 inducers (strength unknown)
Drug Categories	cytochrome p-450 cyp2b6 inducers
Drug Categories	antineoplastic and immunomodulating agents
Drug Categories	antineoplastic agents
Drug Categories	amides
Drug Groups	investigational
Drug Groups	approved
Drug Type	small molecule

(7 More Sources)

Publications:

Ou et al., 2017, Dual occurrence of ALK G1202R solvent front mutation and small cell lung cancer transformation as resistance mechanisms to second generation ALK inhibitors without prior exposure to crizotinib. Pitfall of solely relying on liquid re-biopsy?, Lung Cancer
Shaw et al., 2016, Resensitization to Crizotinib by the Lorlatinib ALK Resistance Mutation L1198F., N. Engl. J. Med.
Infarinato et al., 2016, The ALK/ROS1 Inhibitor PF-06463922 Overcomes Primary Resistance to Crizotinib in ALK-Driven Neuroblastoma., Cancer Discov
Mologni et al., 2015, NPM/ALK mutants resistant to ASP3026 display variable sensitivity to alternative ALK inhibitors but succumb to the novel compound PF-06463922., Oncotarget
Zou et al., 2015, PF-06463922, an ALK/ROS1 Inhibitor, Overcomes Resistance to First and Second Generation ALK Inhibitors in Preclinical Models., Cancer Cell
Gainor et al., 2016, Molecular Mechanisms of Resistance to First- and Second-Generation ALK Inhibitors in ALK-Rearranged Lung Cancer., Cancer Discov
Solomon BJ et al., 2018, Lorlatinib in patients with ALK-positive non-small-cell lung cancer: results from a global phase 2 study., Lancet Oncol
Dagogo-Jack I et al., 2019, Treatment with Next-Generation ALK Inhibitors Fuels Plasma <i>ALK</i> Mutation Diversity., Clin Cancer Res
Pailler E et al., 2019, Acquired Resistance Mutations to ALK Inhibitors Identified by Single Circulating Tumor Cell Sequencing in <i>ALK</i>-Rearranged Non-Small-Cell Lung Cancer., Clin Cancer Res
Redaelli S et al., 2018, Lorlatinib Treatment Elicits Multiple On- and Off-Target Mechanisms of Resistance in ALK-Driven Cancer., Cancer Res
Takahashi K et al., 2020, Overcoming resistance by ALK compound mutation (I1171S + G1269A) after sequential treatment of multiple ALK inhibitors in non-small cell lung cancer., Thorac Cancer
Shaw AT et al., 2017, Lorlatinib in non-small-cell lung cancer with ALK or ROS1 rearrangement: an international, multicentre, open-label, single-arm first-in-man phase 1 trial., Lancet Oncol
Recondo G et al., 2020, Diverse Resistance Mechanisms to the Third-Generation ALK Inhibitor Lorlatinib in ALK-Rearranged Lung Cancer., Clin Cancer Res
Yoda S et al., 2018, Sequential ALK Inhibitors Can Select for Lorlatinib-Resistant Compound <i>ALK</i> Mutations in ALK-Positive Lung Cancer., Cancer Discov
Okada K et al., 2019, Prediction of ALK mutations mediating ALK-TKIs resistance and drug re-purposing to overcome the resistance., EBioMedicine
Planchard D et al., 2018, Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up., Ann Oncol
Planchard D et al., 2019, Correction to: "Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up"., Ann Oncol
Davare MA et al., 2018, Rare but Recurrent ROS1 Fusions Resulting From Chromosome 6q22 Microdeletions are Targetable Oncogenes in Glioma., Clin Cancer Res
Zou et al., 2015, PF-06463922 is a potent and selective next-generation ROS1/ALK inhibitor capable of blocking crizotinib-resistant ROS1 mutations., Proc. Natl. Acad. Sci. U.S.A.
Shaw AT et al., 2019, Lorlatinib in advanced ROS1-positive non-small-cell lung cancer: a multicentre, open-label, single-arm, phase 1-2 trial., Lancet Oncol
Paliouras AR et al., 2020, Vulnerability of drug-resistant EML4-ALK rearranged lung cancer to transcriptional inhibition., EMBO Mol Med

LORLATINIB ALK

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Approval Status Preclinical - Cell line xenograft

Response Type conflicting

Indication/Tumor Type lung cancer

Publications:

Ou et al., 2017, Dual occurrence of ALK G1202R solvent front mutation and small cell lung cancer transformation as resistance mechanisms to second generation ALK inhibitors without prior exposure to crizotinib. Pitfall of solely relying on liquid re-biopsy?, Lung Cancer

Shaw et al., 2016, Resensitization to Crizotinib by the Lorlatinib ALK Resistance Mutation L1198F., N. Engl. J. Med.

Infarinato et al., 2016, The ALK/ROS1 Inhibitor PF-06463922 Overcomes Primary Resistance to Crizotinib in ALK-Driven Neuroblastoma., Cancer Discov

LORLATINIB ROS1

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Indication/Tumor Type non-small cell lung carcinoma

Response Type sensitive

Approval Status Phase I

Publications:

Davare MA et al., 2018, Rare but Recurrent ROS1 Fusions Resulting From Chromosome 6q22 Microdeletions are Targetable Oncogenes in Glioma., Clin Cancer Res

Zou et al., 2015, PF-06463922 is a potent and selective next-generation ROS1/ALK inhibitor capable of blocking crizotinib-resistant ROS1 mutations., Proc. Natl. Acad. Sci. U.S.A.

Shaw AT et al., 2019, Lorlatinib in advanced ROS1-positive non-small-cell lung cancer: a multicentre, open-label, single-arm, phase 1-2 trial., Lancet Oncol

LORLATINIB FES

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? False

Publications:

LORLATINIB RB1

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type lung small cell carcinoma

Response Type predicted – resistant

Approval Status Clinical Study

Publications:

Ou et al., 2017, Dual occurrence of ALK G1202R solvent front mutation and small cell lung cancer transformation as resistance mechanisms to second generation ALK inhibitors without prior exposure to crizotinib. Pitfall of solely relying on liquid re-biopsy?, Lung Cancer

LORLATINIB EML4

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type non-small cell lung carcinoma

Response Type resistant

Approval Status Phase I

Publications:

Infarinato et al., 2016, The ALK/ROS1 Inhibitor PF-06463922 Overcomes Primary Resistance to Crizotinib in ALK-Driven Neuroblastoma., Cancer Discov

Zou et al., 2015, PF-06463922, an ALK/ROS1 Inhibitor, Overcomes Resistance to First and Second Generation ALK Inhibitors in Preclinical Models., Cancer Cell

Gainor et al., 2016, Molecular Mechanisms of Resistance to First- and Second-Generation ALK Inhibitors in ALK-Rearranged Lung Cancer., Cancer Discov

LORLATINIB NPM1

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type Advanced Solid Tumor

Response Type resistant

Approval Status Preclinical

Publications:

Mologni et al., 2015, NPM/ALK mutants resistant to ASP3026 display variable sensitivity to alternative ALK inhibitors but succumb to the novel compound PF-06463922., Oncotarget

LORLATINIB TP53

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type lung small cell carcinoma

Response Type predicted – resistant

Approval Status Clinical Study

Publications:

Ou et al., 2017, Dual occurrence of ALK G1202R solvent front mutation and small cell lung cancer transformation as resistance mechanisms to second generation ALK inhibitors without prior exposure to crizotinib. Pitfall of solely relying on liquid re-biopsy?, Lung Cancer

DrugBank: DB12130
- Version: 5.1.7
Alternate Names:

LORLATINIB DrugBank Drug Name

1454846-35-5 CAS Number

Lorbrena Drug Brand

Drug Info:

Drug Type small molecule

Drug Groups approved

Drug Groups investigational

Publications:

JAX-CKB: Lorlatinib

Version: 15-September-2020

Alternate Names:

Drug Info:

Publications:

Zou et al., 2015, PF-06463922, an ALK/ROS1 Inhibitor, Overcomes Resistance to First and Second Generation ALK Inhibitors in Preclinical Models., Cancer Cell

Shaw et al., 2016, Resensitization to Crizotinib by the Lorlatinib ALK Resistance Mutation L1198F., N. Engl. J. Med.

Infarinato et al., 2016, The ALK/ROS1 Inhibitor PF-06463922 Overcomes Primary Resistance to Crizotinib in ALK-Driven Neuroblastoma., Cancer Discov

GuideToPharmacologyInteractions: 187051779
- Version: 20-July-2020
Alternate Names:

LORLATINIB GuideToPharmacology Ligand Name

Drug Info:

Publications:
TTD: PF-06463922
- Version: 2020.06.01
Alternate Names:

D04DYC TTD Drug ID

Drug Info:

Publications:
TTD: Lorlatinib
- Version: 2020.06.01
Alternate Names:

D0AF6O TTD Drug ID

Drug Info:

Publications:
ChemblDrugs: chembl:CHEMBL3286830
- Version: ChEMBL_27
Alternate Names:

Drug Info:

Publications:
OncoKB: Lorlatinib
- Version: 23-July-2020
Alternate Names:

Drug Info:

Publications:
PharmGKB: lorlatinib
- Version: 18-August-2020
Alternate Names:

Drug Info:

Publications:
FDA: Lorlatinib
- Version: 04-September-2020
Alternate Names:

Drug Info:

Publications:
COSMIC: Lorlatinib
- Version: 4-Sep-2020
Alternate Names:

Drug Info:

Publications:
CGI: Lorlatinib
- Version: 14-September-2020
Alternate Names:

Drug Info:

Publications:

Approval Status	Preclinical - Cell line xenograft
Response Type	conflicting
Indication/Tumor Type	lung cancer

Indication/Tumor Type	non-small cell lung carcinoma
Response Type	sensitive
Approval Status	Phase I

Specific Action of the Ligand	Inhibition
Endogenous Drug?	False
Direct Interaction?	False

Indication/Tumor Type	lung small cell carcinoma
Response Type	predicted – resistant
Approval Status	Clinical Study

Indication/Tumor Type	Advanced Solid Tumor
Response Type	resistant
Approval Status	Preclinical

LORLATINIB	DrugBank Drug Name
1454846-35-5	CAS Number
Lorbrena	Drug Brand

LORLATINIB Drug Record

LORLATINIB chembl:CHEMBL3286830 ApprovedAntineoplastic

Alternate Names:

Drug Info:

Publications:

LORLATINIB ALK

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Approval Status Preclinical - Cell line xenograft Response Type conflicting Indication/Tumor Type lung cancer

LORLATINIB ROS1

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Indication/Tumor Type non-small cell lung carcinoma Response Type sensitive Approval Status Phase I

LORLATINIB FES

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Specific Action of the Ligand Inhibition Endogenous Drug? False Direct Interaction? False

Publications:

LORLATINIB RB1

Interaction Types & Directionality: n/a

Interaction Info: Indication/Tumor Type lung small cell carcinoma Response Type predicted – resistant Approval Status Clinical Study

Publications: Ou et al., 2017, Dual occurrence of ALK G1202R solvent front mutation and small cell lung cancer transformation as resistance mechanisms to second generation ALK inhibitors without prior exposure to crizotinib. Pitfall of solely relying on liquid re-biopsy?, Lung Cancer

LORLATINIB EML4

Interaction Types & Directionality: n/a

Interaction Info: Indication/Tumor Type non-small cell lung carcinoma Response Type resistant Approval Status Phase I

LORLATINIB NPM1

Interaction Types & Directionality: n/a

Interaction Info: Indication/Tumor Type Advanced Solid Tumor Response Type resistant Approval Status Preclinical

Publications: Mologni et al., 2015, NPM/ALK mutants resistant to ASP3026 display variable sensitivity to alternative ALK inhibitors but succumb to the novel compound PF-06463922., Oncotarget

LORLATINIB TP53

Interaction Types & Directionality: n/a

Interaction Info: Indication/Tumor Type lung small cell carcinoma Response Type predicted – resistant Approval Status Clinical Study

Publications: Ou et al., 2017, Dual occurrence of ALK G1202R solvent front mutation and small cell lung cancer transformation as resistance mechanisms to second generation ALK inhibitors without prior exposure to crizotinib. Pitfall of solely relying on liquid re-biopsy?, Lung Cancer

DrugBank: DB12130

Alternate Names: LORLATINIB DrugBank Drug Name 1454846-35-5 CAS Number Lorbrena Drug Brand

Drug Info: Drug Type small molecule Drug Groups approved Drug Groups investigational

Publications:

JAX-CKB: Lorlatinib

Alternate Names:

Drug Info:

GuideToPharmacologyInteractions: 187051779

Alternate Names: LORLATINIB GuideToPharmacology Ligand Name

Drug Info:

Publications:

TTD: PF-06463922

Alternate Names: D04DYC TTD Drug ID

Drug Info:

Publications:

TTD: Lorlatinib

Alternate Names: D0AF6O TTD Drug ID

Drug Info:

Publications:

ChemblDrugs: chembl:CHEMBL3286830

Alternate Names:

Drug Info:

Publications:

OncoKB: Lorlatinib

Alternate Names:

Drug Info:

Publications:

PharmGKB: lorlatinib

Alternate Names:

Drug Info:

Publications:

FDA: Lorlatinib

Alternate Names:

Drug Info:

Publications:

COSMIC: Lorlatinib

Alternate Names:

Drug Info:

Publications:

CGI: Lorlatinib

Alternate Names:

Drug Info:

Publications:

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Approval Status Preclinical - Cell line xenograft

Response Type conflicting

Indication/Tumor Type lung cancer

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Indication/Tumor Type non-small cell lung carcinoma

Response Type sensitive

Approval Status Phase I

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? False

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type lung small cell carcinoma

Response Type predicted – resistant

Approval Status Clinical Study

Publications:

Ou et al., 2017, Dual occurrence of ALK G1202R solvent front mutation and small cell lung cancer transformation as resistance mechanisms to second generation ALK inhibitors without prior exposure to crizotinib. Pitfall of solely relying on liquid re-biopsy?, Lung Cancer

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type non-small cell lung carcinoma

Response Type resistant

Approval Status Phase I

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type Advanced Solid Tumor

Response Type resistant

Approval Status Preclinical

Publications:

Mologni et al., 2015, NPM/ALK mutants resistant to ASP3026 display variable sensitivity to alternative ALK inhibitors but succumb to the novel compound PF-06463922., Oncotarget

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type lung small cell carcinoma

Response Type predicted – resistant

Approval Status Clinical Study

Publications:

Ou et al., 2017, Dual occurrence of ALK G1202R solvent front mutation and small cell lung cancer transformation as resistance mechanisms to second generation ALK inhibitors without prior exposure to crizotinib. Pitfall of solely relying on liquid re-biopsy?, Lung Cancer

Alternate Names:

LORLATINIB DrugBank Drug Name

1454846-35-5 CAS Number

Lorbrena Drug Brand

Drug Info:

Drug Type small molecule

Drug Groups approved

Drug Groups investigational

Alternate Names:

LORLATINIB GuideToPharmacology Ligand Name

Alternate Names:

D04DYC TTD Drug ID

Alternate Names:

D0AF6O TTD Drug ID