Lorlatinib

Lorlatinib, sold under the brand name Lorbrena in the United States, Canada, and Japan, and Lorviqua in the European Union, is an anti-cancer medication used for the treatment of non-small cell lung cancer.[4] It is an orally administered inhibitor of anaplastic lymphoma kinase (ALK) and C-ros oncogene 1 (ROS1), two enzymes that play a role in the development of cancer.[5] Lorlatinib is indicated for the treatment of adults with metastatic non-small cell lung cancer whose tumors are anaplastic lymphoma kinase (ALK)-positive.Inhibitors of these enzymes such as ketoconazole or grapefruit juice increase lorlatinib plasma concentrations, leading to higher toxicity.In 2015, the FDA granted lorlatinib orphan drug status for the treatment of anaplastic lymphoma kinase (ALK)-positive or ROS1-positive non-small cell lung cancer.

Lorlatinib is cleaved to the metabolite M8 (top left), which makes up 21% of the circulating substance, and an undetected metabolite (given in brackets). Other phase I metabolites are given in the bottom row. Most of these metabolites, as well as the original substance, undergo glucuronidation . ^{[

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Drugs.comMedlinePlusLicense dataDailyMedPregnancycategoryRoutes ofadministrationBy mouthATC codeL01ED05Legal status ℞-only℞-onlyPharmacokineticBioavailabilityProtein bindingMetabolismCYP3A4UGT1A4Elimination half-lifeExcretionIUPAC nameCAS NumberDrugBankChemSpiderCompTox DashboardECHA InfoCardFormulaMolar massSMILESanti-cancer medicationnon-small cell lung canceranaplastic lymphoma kinaseC-ros oncogene 1Pfizerindicatedinducersliver toxicityrifampicinhigh blood cholesterolhigh blood triglyceridesperipheral neuropathycognitivefatiguecarbamazepineSt John's wortblood plasmaketoconazolegrapefruit juicemidazolamciclosporinin vitroCYP2C9UGT1A1transport proteinsCYP2B6CYP1A2ALK inhibitorsmall moleculekinase inhibitorkinasesmetabolitephase I metabolitesglucuronidationplasma proteinsblood–brain barrieroxidationmetaboliteshydrochloric acidFood and Drug Administrationorphan drug statusHealth CanadaEuropean Medicines Agencypublic domainClinicalTrials.govTargeted cancer therapyantineoplastic agentsmonoclonal antibodiesReceptor tyrosine kinaseHER1/EGFRCetuximabPanitumumabHER2/neuPertuzumabTrastuzumab+hyaluronidaseTrastuzumab emtansineTrastuzumab deruxtecanZanidatamabCatumaxomabEdrecolomabVEGF-ABevacizumabLeukemialymphomalymphoidGlofitamabElranatamabMosunetuzumabIbritumomabObinutuzumabOfatumumabRituximabTositumomabBrentuximabAlemtuzumabmyeloidGemtuzumab ozogamicinAmivantamabAtezolizumabAvelumabAxatilimabBelantamab mafodotinBermekimabBlinatumomabCemiplimabCosibelimabDaratumumabDinutuximab betaDostarlimabDurvalumabElotuzumabEnfortumab vedotinEpcoritamabInotuzumab ozogamicinIpilimumabIsatuximabLoncastuximab tesirineMirvetuximab soravtansineMogamulizumabMoxetumomab pasudotoxNaxitamabNecitumumabNivolumab+relatlimabOlaratumabOportuzumab monatoxPembrolizumabPolatuzumab vedotinRamucirumabRetifanlimabSacituzumab govitecanSerplulimabSugemalimabTafasitamabTalquetamabTarlatamabTeclistamabTislelizumabTisotumab vedotinToripalimabTremelimumabZenocutuzumabZolbetuximabTyrosine kinase inhibitorsAfatinibAumolertinibBrigatinibDacomitinibErlotinibGefitinibIcotinibLazertinibMobocertinibOlmutinibOsimertinibRociletinibVandetanibLapatinibNeratinibTucatinibDabrafenibEncorafenibTovorafenibVemurafenibRTK class IIIAvapritinibAxitinibMasitinibPazopanibRipretinibSorafenibSunitinibToceranibLestaurtinibGilteritinibCediranibFruquintinibLenvatinibNintedanibRegorafenibSemaxanibTivozanibAlectinibCeritinibCrizotinibEnsartinibEntrectinibFutibatinibInfigratinib