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Identification
NameCeritinib
Accession NumberDB09063
TypeSmall Molecule
GroupsApproved
Description

Ceritinib is used for the treatment of adults with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) following failure (secondary to resistance or intolerance) of prior crizotinib therapy. About 4% of patients with NSCLC have a chromosomal rearrangement that generates a fusion gene between EML4 (echinoderm microtubule-associated protein-like 4) and ALK (anaplastic lymphoma kinase), which results in constitutive kinase activity that contributes to carcinogenesis and seems to drive the malignant phenotype. Ceritinib exerts its therapeutic effect by inhibiting autophosphorylation of ALK, ALK-mediated phosphorylation of the downstream signaling protein STAT3, and proliferation of ALK-dependent cancer cells. Following treatment with crizotinib (a first-generation ALK inhibitor), most tumours develop drug resistance due to mutations in key “gatekeeper” residues of the enzyme. This occurrence led to development of novel second-generation ALK inhibitors such as ceritinib to overcome crizotinib resistance. The FDA approved ceritinib in April 2014 due to a surprisingly high response rate (56%) towards crizotinib-resistant tumours and has designated it with orphan drug status.

Structure
Thumb
Synonyms
céritinib
N-{2-[(5-chloro-2-{[2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl]amino}pyrimidin-4-yl)amino]phenyl}propane-2-sulfonamide
External Identifiers
  • LDK 378
  • LDK-378
  • LDK378
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Zykadiacapsule150 mg/1oralNovartis Pharmaceuticals Corporation2014-04-29Not applicableUs
Zykadiacapsule150 mgoralNovartis Pharmaceuticals Canada Inc2015-04-29Not applicableCanada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIK418KG2GET
CAS number1032900-25-6
WeightAverage: 558.135
Monoisotopic: 557.22273844
Chemical FormulaC28H36ClN5O3S
InChI KeyVERWOWGGCGHDQE-UHFFFAOYSA-N
InChI
InChI=1S/C28H36ClN5O3S/c1-17(2)37-25-15-21(20-10-12-30-13-11-20)19(5)14-24(25)33-28-31-16-22(29)27(34-28)32-23-8-6-7-9-26(23)38(35,36)18(3)4/h6-9,14-18,20,30H,10-13H2,1-5H3,(H2,31,32,33,34)
IUPAC Name
5-chloro-N2-[5-methyl-4-(piperidin-4-yl)-2-(propan-2-yloxy)phenyl]-N4-[2-(propane-2-sulfonyl)phenyl]pyrimidine-2,4-diamine
SMILES
CC(C)OC1=C(NC2=NC=C(Cl)C(N2)=NC2=CC=CC=C2S(=O)(=O)C(C)C)C=C(C)C(=C1)C1CCNCC1
Taxonomy
ClassificationNot classified
Pharmacology
IndicationCeritinib is a kinase inhibitor indicated for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib. This indication is approved under accelerated approval based on tumor response rate and duration of response. An improvement in survival or disease-related symptoms has not been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
PharmacodynamicsNot Available
Mechanism of actionCeritinib inhibits Anaplastic lymphoma kinase (ALK) also known as ALK tyrosine kinase receptor or CD246 (cluster of differentiation 246), which is an enzyme that in humans is encoded by the ALK gene. About 4-5% of NSCLCs have a chromosomal rearrangement that generates a fusion gene between EML4 (echinoderm microtubule-associated protein-like 4) and ALK (anaplastic lymphoma kinase), which results in constitutive kinase activity that contributes to carcinogenesis and seems to drive the malignant phenotype. Ceritinib exerts its therapeutic effect by inhibiting autophosphorylation of ALK, ALK-mediated phosphorylation of the downstream signaling protein STAT3, and proliferation of ALK-dependent cancer cells. Ceritinib has been shown to inhibit in vitro proliferation of cell lines expressing EML4-ALK and NPM-ALK fusion proteins and demonstrated dose-dependent inhibition of EML4-ALK-positive NSCLC xenograft growth in mice and rats.
Related Articles
AbsorptionAfter oral administration of ceritinib, peak concentrations were achieved after approximately 4 to 6 hours.
Volume of distribution

The apparent volume of distribution (Vd/F) is 4230 L following a single 750 mg dose.

Protein bindingCeritinib is 97% bound to human plasma proteins, independent of drug concentration.
Metabolism

In vitro studies demonstrated that CYP3A was the major enzyme involved in the metabolic clearance of ceritinib. Following oral administration of a single 750 mg radiolabeled ceritinib dose, ceritinib as the parent compound was the main circulating component (82%) in human plasma.

Route of eliminationFollowing oral administration of a single 750 mg radiolabeled ceritinib dose, 92.3% of the administered dose was recovered in the feces (with 68% as unchanged parent compound) while 1.3% of the administered dose was recovered in the urine.
Half lifeThe terminal half life is 41 hours.
Clearance

The geometric mean apparent clearance (CL/F) of ceritinib was lower at steady-state (33.2 L/h) after 750 mg daily dosing than after a single 750 mg dose (88.5 L/h).

ToxicityThere is not currently any data on carcinogenicity, effect on human fertility, or on early embryonic development. However, based on its mechanism of action, ceritinib may cause fetal harm when administered to pregnant women and should therefore be administered with effective contraception during treatment. Diarrhea, nausea, vomiting, or abdominal pain occurred in 96% of 255 patients including severe cases in 14% of patients. Drug-induced hepatotoxicity also occurred in 27% of 255 patients, presenting as alanine aminotransferase (ALT) levels greater than 5 times the upper limit of normal (ULN). Severe, life-threatening, or fatal interstitial lung disease (ILD)/pneumonitis, hyperglycaemia, and bradycardia have also been reported.
Affected organismsNot Available
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal AbsorptionNot AvailableNot Available
Blood Brain BarrierNot AvailableNot Available
Caco-2 permeableNot AvailableNot Available
P-glycoprotein substrateNot AvailableNot Available
P-glycoprotein inhibitor INot AvailableNot Available
P-glycoprotein inhibitor IINot AvailableNot Available
Renal organic cation transporterNot AvailableNot Available
CYP450 2C9 substrateNot AvailableNot Available
CYP450 2D6 substrateNot AvailableNot Available
CYP450 3A4 substrateNot AvailableNot Available
CYP450 1A2 substrateNot AvailableNot Available
CYP450 2C9 inhibitorNot AvailableNot Available
CYP450 2D6 inhibitorNot AvailableNot Available
CYP450 2C19 inhibitorNot AvailableNot Available
CYP450 3A4 inhibitorNot AvailableNot Available
CYP450 inhibitory promiscuityNot AvailableNot Available
Ames testNot AvailableNot Available
CarcinogenicityNot AvailableNot Available
BiodegradationNot AvailableNot Available
Rat acute toxicityNot AvailableNot applicable
hERG inhibition (predictor I)Not AvailableNot Available
hERG inhibition (predictor II)Not AvailableNot Available
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Capsuleoral150 mg/1
Capsuleoral150 mg
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7153964 No2001-02-262021-02-26Us
US7893074 No2006-04-252026-04-25Us
US7964592 No2007-01-132027-01-13Us
US8039474 No2010-06-292030-06-29Us
US8039479 No2010-06-292030-06-29Us
US8377921 No2007-11-202027-11-20Us
US8703787 No2012-02-022032-02-02Us
US9309229 No2012-01-182032-01-18Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
pKa9.7 and 4.1FDA Label
Predicted Properties
PropertyValueSource
Water Solubility0.00222 mg/mLALOGPS
logP5.23ALOGPS
logP5.81ChemAxon
logS-5.4ALOGPS
pKa (Strongest Acidic)11.58ChemAxon
pKa (Strongest Basic)10.07ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area105.24 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity153.86 m3·mol-1ChemAxon
Polarizability61.33 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference
  1. Marsilje TH, Pei W, Chen B, Lu W, Uno T, Jin Y, Jiang T, Kim S, Li N, Warmuth M, Sarkisova Y, Sun F, Steffy A, Pferdekamper AC, Li AG, Joseph SB, Kim Y, Liu B, Tuntland T, Cui X, Gray NS, Steensma R, Wan Y, Jiang J, Chopiuk G, Li J, Gordon WP, Richmond W, Johnson K, Chang J, Groessl T, He YQ, Phimister A, Aycinena A, Lee CC, Bursulaya B, Karanewsky DS, Seidel HM, Harris JL, Michellys PY: Synthesis, structure-activity relationships, and in vivo efficacy of the novel potent and selective anaplastic lymphoma kinase (ALK) inhibitor 5-chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(2-(isopropylsulf onyl)phenyl)pyrimidine-2,4-diamine (LDK378) currently in phase 1 and phase 2 clinical trials. J Med Chem. 2013 Jul 25;56(14):5675-90. doi: 10.1021/jm400402q. Epub 2013 Jun 26. Pubmed
General References
  1. Shaw AT, Kim DW, Mehra R, Tan DS, Felip E, Chow LQ, Camidge DR, Vansteenkiste J, Sharma S, De Pas T, Riely GJ, Solomon BJ, Wolf J, Thomas M, Schuler M, Liu G, Santoro A, Lau YY, Goldwasser M, Boral AL, Engelman JA: Ceritinib in ALK-rearranged non-small-cell lung cancer. N Engl J Med. 2014 Mar 27;370(13):1189-97. doi: 10.1056/NEJMoa1311107. [PubMed:24670165 ]
  2. Nishio M, Murakami H, Horiike A, Takahashi T, Hirai F, Suenaga N, Tajima T, Tokushige K, Ishii M, Boral A, Robson M, Seto T: Phase I Study of Ceritinib (LDK378) in Japanese Patients with Advanced, Anaplastic Lymphoma Kinase-Rearranged Non-Small-Cell Lung Cancer or Other Tumors. J Thorac Oncol. 2015 Jul;10(7):1058-66. doi: 10.1097/JTO.0000000000000566. [PubMed:26020125 ]
  3. Galkin AV, Melnick JS, Kim S, Hood TL, Li N, Li L, Xia G, Steensma R, Chopiuk G, Jiang J, Wan Y, Ding P, Liu Y, Sun F, Schultz PG, Gray NS, Warmuth M: Identification of NVP-TAE684, a potent, selective, and efficacious inhibitor of NPM-ALK. Proc Natl Acad Sci U S A. 2007 Jan 2;104(1):270-5. Epub 2006 Dec 21. [PubMed:17185414 ]
  4. Marsilje TH, Pei W, Chen B, Lu W, Uno T, Jin Y, Jiang T, Kim S, Li N, Warmuth M, Sarkisova Y, Sun F, Steffy A, Pferdekamper AC, Li AG, Joseph SB, Kim Y, Liu B, Tuntland T, Cui X, Gray NS, Steensma R, Wan Y, Jiang J, Chopiuk G, Li J, Gordon WP, Richmond W, Johnson K, Chang J, Groessl T, He YQ, Phimister A, Aycinena A, Lee CC, Bursulaya B, Karanewsky DS, Seidel HM, Harris JL, Michellys PY: Synthesis, structure-activity relationships, and in vivo efficacy of the novel potent and selective anaplastic lymphoma kinase (ALK) inhibitor 5-chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(2-(isopropylsulf onyl)phenyl)pyrimidine-2,4-diamine (LDK378) currently in phase 1 and phase 2 clinical trials. J Med Chem. 2013 Jul 25;56(14):5675-90. doi: 10.1021/jm400402q. Epub 2013 Jun 26. [PubMed:23742252 ]
  5. Mano H: The EML4-ALK oncogene: targeting an essential growth driver in human cancer. Proc Jpn Acad Ser B Phys Biol Sci. 2015;91(5):193-201. doi: 10.2183/pjab.91.193. [PubMed:25971657 ]
External Links
ATC CodesL01XE28
AHFS Codes
  • 10:00
PDB Entries
FDA labelDownload (307 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AcebutololAcebutolol may increase the bradycardic activities of Ceritinib.
AcenocoumarolThe serum concentration of Acenocoumarol can be increased when it is combined with Ceritinib.
AcetohexamideThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Ceritinib.
AlclometasoneAlclometasone may increase the hyperglycemic activities of Ceritinib.
AlfuzosinThe serum concentration of Alfuzosin can be increased when it is combined with Ceritinib.
AlmotriptanThe serum concentration of Almotriptan can be increased when it is combined with Ceritinib.
AlogliptinThe therapeutic efficacy of Alogliptin can be decreased when used in combination with Ceritinib.
AlosetronThe serum concentration of Alosetron can be increased when it is combined with Ceritinib.
AmcinonideAmcinonide may increase the hyperglycemic activities of Ceritinib.
AmiodaroneAmiodarone may increase the bradycardic activities of Ceritinib.
ApixabanThe serum concentration of Apixaban can be increased when it is combined with Ceritinib.
AripiprazoleThe serum concentration of Aripiprazole can be increased when it is combined with Ceritinib.
AstemizoleThe serum concentration of Astemizole can be increased when it is combined with Ceritinib.
AtazanavirThe serum concentration of Ceritinib can be increased when it is combined with Atazanavir.
AtenololAtenolol may increase the bradycardic activities of Ceritinib.
AvanafilThe serum concentration of Avanafil can be increased when it is combined with Ceritinib.
AxitinibThe serum concentration of Axitinib can be increased when it is combined with Ceritinib.
BarnidipineThe serum concentration of Barnidipine can be increased when it is combined with Ceritinib.
Beclomethasone dipropionateBeclomethasone may increase the hyperglycemic activities of Ceritinib.
BedaquilineThe serum concentration of Bedaquiline can be increased when it is combined with Ceritinib.
BeractantBeractant may increase the bradycardic activities of Ceritinib.
BetamethasoneBetamethasone may increase the hyperglycemic activities of Ceritinib.
BetaxololBetaxolol may increase the bradycardic activities of Ceritinib.
BexaroteneThe serum concentration of Ceritinib can be decreased when it is combined with Bexarotene.
BisoprololBisoprolol may increase the bradycardic activities of Ceritinib.
BoceprevirThe serum concentration of Ceritinib can be increased when it is combined with Boceprevir.
BortezomibThe serum concentration of Bortezomib can be increased when it is combined with Ceritinib.
BosentanThe serum concentration of Ceritinib can be decreased when it is combined with Bosentan.
BosutinibThe serum concentration of Bosutinib can be increased when it is combined with Ceritinib.
Brentuximab vedotinThe serum concentration of Brentuximab vedotin can be increased when it is combined with Ceritinib.
BretyliumBretylium may increase the bradycardic activities of Ceritinib.
BrexpiprazoleThe serum concentration of Brexpiprazole can be increased when it is combined with Ceritinib.
BrinzolamideThe serum concentration of Brinzolamide can be increased when it is combined with Ceritinib.
BudesonideThe serum concentration of Budesonide can be increased when it is combined with Ceritinib.
CabazitaxelThe serum concentration of Cabazitaxel can be increased when it is combined with Ceritinib.
CabozantinibThe serum concentration of Cabozantinib can be increased when it is combined with Ceritinib.
CalcitriolThe serum concentration of Calcitriol can be increased when it is combined with Ceritinib.
CalfactantCalfactant may increase the bradycardic activities of Ceritinib.
CanagliflozinThe therapeutic efficacy of Canagliflozin can be decreased when used in combination with Ceritinib.
CarbamazepineThe serum concentration of Ceritinib can be decreased when it is combined with Carbamazepine.
CarteololCarteolol may increase the bradycardic activities of Ceritinib.
CarvedilolCarvedilol may increase the bradycardic activities of Ceritinib.
CelecoxibThe serum concentration of Celecoxib can be increased when it is combined with Ceritinib.
ChlorpropamideThe serum concentration of Chlorpropamide can be increased when it is combined with Ceritinib.
CiclesonideCiclesonide may increase the hyperglycemic activities of Ceritinib.
CilostazolThe serum concentration of Cilostazol can be increased when it is combined with Ceritinib.
CitalopramCeritinib may increase the QTc-prolonging activities of Citalopram.
ClarithromycinThe serum concentration of Ceritinib can be increased when it is combined with Clarithromycin.
Clobetasol propionateClobetasol propionate may increase the hyperglycemic activities of Ceritinib.
ClocortoloneClocortolone may increase the hyperglycemic activities of Ceritinib.
ClonidineClonidine may increase the bradycardic activities of Ceritinib.
CobicistatThe serum concentration of Ceritinib can be increased when it is combined with Cobicistat.
ColchicineThe serum concentration of Colchicine can be increased when it is combined with Ceritinib.
ConivaptanThe serum concentration of Conivaptan can be increased when it is combined with Ceritinib.
CorticotropinCorticotropin may increase the hyperglycemic activities of Ceritinib.
Cortisone acetateCortisone acetate may increase the hyperglycemic activities of Ceritinib.
CrizotinibCrizotinib may increase the bradycardic activities of Ceritinib.
DabrafenibThe serum concentration of Ceritinib can be decreased when it is combined with Dabrafenib.
DaclatasvirThe serum concentration of Daclatasvir can be increased when it is combined with Ceritinib.
DapoxetineThe serum concentration of Dapoxetine can be increased when it is combined with Ceritinib.
DarunavirThe serum concentration of Ceritinib can be increased when it is combined with Darunavir.
DasatinibThe serum concentration of Dasatinib can be increased when it is combined with Ceritinib.
DeferasiroxThe serum concentration of Ceritinib can be decreased when it is combined with Deferasirox.
DesonideDesonide may increase the hyperglycemic activities of Ceritinib.
DesoximetasoneDesoximetasone may increase the hyperglycemic activities of Ceritinib.
DexmedetomidineDexmedetomidine may increase the bradycardic activities of Ceritinib.
DienogestThe serum concentration of Dienogest can be increased when it is combined with Ceritinib.
DiflorasoneDiflorasone may increase the hyperglycemic activities of Ceritinib.
DifluprednateDifluprednate may increase the hyperglycemic activities of Ceritinib.
DigoxinDigoxin may increase the bradycardic activities of Ceritinib.
DiltiazemDiltiazem may increase the bradycardic activities of Ceritinib.
DofetilideCeritinib may increase the QTc-prolonging activities of Dofetilide.
DomperidoneThe serum concentration of Domperidone can be increased when it is combined with Ceritinib.
DonepezilDonepezil may increase the bradycardic activities of Ceritinib.
DoxorubicinThe serum concentration of Doxorubicin can be increased when it is combined with Ceritinib.
DronabinolThe serum concentration of Dronabinol can be increased when it is combined with Ceritinib.
DronedaroneDronedarone may increase the bradycardic activities of Ceritinib.
DrospirenoneThe serum concentration of Drospirenone can be increased when it is combined with Ceritinib.
DutasterideThe serum concentration of Dutasteride can be increased when it is combined with Ceritinib.
EletriptanThe serum concentration of Eletriptan can be increased when it is combined with Ceritinib.
EnzalutamideThe serum concentration of Ceritinib can be decreased when it is combined with Enzalutamide.
EplerenoneThe serum concentration of Eplerenone can be increased when it is combined with Ceritinib.
ErlotinibThe serum concentration of Erlotinib can be increased when it is combined with Ceritinib.
EsmololEsmolol may increase the bradycardic activities of Ceritinib.
EstazolamThe serum concentration of Estazolam can be increased when it is combined with Ceritinib.
EtizolamThe serum concentration of Etizolam can be increased when it is combined with Ceritinib.
EverolimusThe serum concentration of Everolimus can be increased when it is combined with Ceritinib.
FentanylThe serum concentration of Fentanyl can be increased when it is combined with Ceritinib.
FesoterodineThe serum concentration of the active metabolites of Fesoterodine can be increased when Fesoterodine is used in combination with Ceritinib.
FingolimodFingolimod may increase the bradycardic activities of Ceritinib.
FlibanserinThe serum concentration of Flibanserin can be increased when it is combined with Ceritinib.
FluconazoleThe metabolism of Ceritinib can be decreased when combined with Fluconazole.
FludrocortisoneFludrocortisone may increase the hyperglycemic activities of Ceritinib.
FlunisolideFlunisolide may increase the hyperglycemic activities of Ceritinib.
Fluocinolone AcetonideFluocinolone Acetonide may increase the hyperglycemic activities of Ceritinib.
FluocinonideFluocinonide may increase the hyperglycemic activities of Ceritinib.
FluorometholoneFluorometholone may increase the hyperglycemic activities of Ceritinib.
FlurandrenolideFlurandrenolide may increase the hyperglycemic activities of Ceritinib.
Fluticasone furoateFluticasone furoate may increase the hyperglycemic activities of Ceritinib.
Fluticasone PropionateThe serum concentration of Fluticasone Propionate can be increased when it is combined with Ceritinib.
FosphenytoinThe serum concentration of Ceritinib can be decreased when it is combined with Fosphenytoin.
Fusidic AcidThe serum concentration of Ceritinib can be increased when it is combined with Fusidic Acid.
GalantamineGalantamine may increase the bradycardic activities of Ceritinib.
GliclazideThe serum concentration of Gliclazide can be increased when it is combined with Ceritinib.
GlimepirideThe serum concentration of Glimepiride can be increased when it is combined with Ceritinib.
GlipizideThe serum concentration of Glipizide can be increased when it is combined with Ceritinib.
GliquidoneThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Ceritinib.
GlyburideThe serum concentration of Glyburide can be increased when it is combined with Ceritinib.
GoserelinGoserelin may increase the QTc-prolonging activities of Ceritinib.
GuanfacineGuanfacine may increase the bradycardic activities of Ceritinib.
HalcinonideHalcinonide may increase the hyperglycemic activities of Ceritinib.
HalofantrineThe serum concentration of Halofantrine can be increased when it is combined with Ceritinib.
HydrocodoneThe serum concentration of Hydrocodone can be increased when it is combined with Ceritinib.
HydrocortamateHydrocortamate may increase the hyperglycemic activities of Ceritinib.
HydrocortisoneHydrocortisone may increase the hyperglycemic activities of Ceritinib.
IbrutinibThe serum concentration of Ibrutinib can be increased when it is combined with Ceritinib.
IdelalisibThe serum concentration of Ceritinib can be increased when it is combined with Idelalisib.
IfosfamideThe serum concentration of the active metabolites of Ifosfamide can be reduced when Ifosfamide is used in combination with Ceritinib resulting in a loss in efficacy.
ImatinibThe serum concentration of Imatinib can be increased when it is combined with Ceritinib.
ImidafenacinThe serum concentration of Imidafenacin can be increased when it is combined with Ceritinib.
IndinavirThe serum concentration of Ceritinib can be increased when it is combined with Indinavir.
Insulin AspartThe therapeutic efficacy of Insulin Aspart can be decreased when used in combination with Ceritinib.
Insulin DetemirThe therapeutic efficacy of Insulin Detemir can be decreased when used in combination with Ceritinib.
Insulin GlargineThe therapeutic efficacy of Insulin Glargine can be decreased when used in combination with Ceritinib.
Insulin GlulisineThe therapeutic efficacy of Insulin Glulisine can be decreased when used in combination with Ceritinib.
Insulin HumanThe therapeutic efficacy of Insulin Regular can be decreased when used in combination with Ceritinib.
Insulin LisproThe therapeutic efficacy of Insulin Lispro can be decreased when used in combination with Ceritinib.
IrinotecanThe serum concentration of the active metabolites of Irinotecan can be increased when Irinotecan is used in combination with Ceritinib.
IsavuconazoniumThe serum concentration of the active metabolites of Isavuconazonium can be increased when Isavuconazonium is used in combination with Ceritinib.
ItraconazoleThe serum concentration of Ceritinib can be increased when it is combined with Itraconazole.
IvabradineThe serum concentration of Ivabradine can be increased when it is combined with Ceritinib.
IvacaftorThe serum concentration of Ivacaftor can be increased when it is combined with Ceritinib.
IxabepiloneThe serum concentration of Ixabepilone can be increased when it is combined with Ceritinib.
KetoconazoleThe serum concentration of Ceritinib can be increased when it is combined with Ketoconazole.
LabetalolLabetalol may increase the bradycardic activities of Ceritinib.
LacosamideThe serum concentration of Lacosamide can be increased when it is combined with Ceritinib.
LanreotideLanreotide may increase the bradycardic activities of Ceritinib.
LapatinibThe serum concentration of Lapatinib can be increased when it is combined with Ceritinib.
LercanidipineThe serum concentration of Lercanidipine can be increased when it is combined with Ceritinib.
LeuprolideLeuprolide may increase the QTc-prolonging activities of Ceritinib.
LevobunololLevobunolol may increase the bradycardic activities of Ceritinib.
LevobupivacaineThe serum concentration of Levobupivacaine can be increased when it is combined with Ceritinib.
LevomilnacipranThe serum concentration of Levomilnacipran can be increased when it is combined with Ceritinib.
LinagliptinThe therapeutic efficacy of Linagliptin can be decreased when used in combination with Ceritinib.
LomitapideThe serum concentration of Lomitapide can be increased when it is combined with Ceritinib.
LosartanThe serum concentration of Losartan can be increased when it is combined with Ceritinib.
LoteprednolLoteprednol may increase the hyperglycemic activities of Ceritinib.
LovastatinThe serum concentration of Lovastatin can be increased when it is combined with Ceritinib.
LucinactantLucinactant may increase the bradycardic activities of Ceritinib.
LuliconazoleThe serum concentration of Ceritinib can be increased when it is combined with Luliconazole.
LurasidoneThe serum concentration of Lurasidone can be increased when it is combined with Ceritinib.
MacitentanThe serum concentration of MACITENTAN can be increased when it is combined with Ceritinib.
MaravirocThe serum concentration of Maraviroc can be increased when it is combined with Ceritinib.
Medroxyprogesterone acetateThe serum concentration of Medroxyprogesterone Acetate can be increased when it is combined with Ceritinib.
MeloxicamThe serum concentration of Meloxicam can be increased when it is combined with Ceritinib.
MetforminThe therapeutic efficacy of Metformin can be decreased when used in combination with Ceritinib.
MethyldopaMethyldopa may increase the bradycardic activities of Ceritinib.
MethylprednisoloneThe serum concentration of Methylprednisolone can be increased when it is combined with Ceritinib.
MetipranololMetipranolol may increase the bradycardic activities of Ceritinib.
MetoprololMetoprolol may increase the bradycardic activities of Ceritinib.
MifepristoneMifepristone may increase the QTc-prolonging activities of Ceritinib.
MitotaneThe serum concentration of Ceritinib can be decreased when it is combined with Mitotane.
MometasoneMometasone may increase the hyperglycemic activities of Ceritinib.
NadololNadolol may increase the bradycardic activities of Ceritinib.
NaloxegolThe serum concentration of Naloxegol can be increased when it is combined with Ceritinib.
NebivololNebivolol may increase the bradycardic activities of Ceritinib.
NefazodoneThe serum concentration of Ceritinib can be increased when it is combined with Nefazodone.
NelfinavirThe serum concentration of Ceritinib can be increased when it is combined with Nelfinavir.
NetupitantThe serum concentration of Ceritinib can be increased when it is combined with Netupitant.
NilotinibThe serum concentration of Nilotinib can be increased when it is combined with Ceritinib.
NimodipineThe serum concentration of Nimodipine can be increased when it is combined with Ceritinib.
NisoldipineThe serum concentration of Nisoldipine can be increased when it is combined with Ceritinib.
OctreotideOctreotide may increase the bradycardic activities of Ceritinib.
OlaparibThe serum concentration of Olaparib can be increased when it is combined with Ceritinib.
OspemifeneThe serum concentration of Ospemifene can be increased when it is combined with Ceritinib.
OxybutyninThe serum concentration of Oxybutynin can be increased when it is combined with Ceritinib.
OxycodoneThe risk or severity of adverse effects can be increased when Ceritinib is combined with Oxycodone.
PalbociclibThe serum concentration of Palbociclib can be increased when it is combined with Ceritinib.
PanobinostatThe serum concentration of Panobinostat can be increased when it is combined with Ceritinib.
ParecoxibThe serum concentration of Parecoxib can be increased when it is combined with Ceritinib.
ParicalcitolThe serum concentration of Paricalcitol can be increased when it is combined with Ceritinib.
PasireotidePasireotide may increase the bradycardic activities of Ceritinib.
PazopanibThe serum concentration of Pazopanib can be increased when it is combined with Ceritinib.
PenbutololPenbutolol may increase the bradycardic activities of Ceritinib.
PhenobarbitalThe serum concentration of Ceritinib can be decreased when it is combined with Phenobarbital.
PhenytoinThe serum concentration of Ceritinib can be decreased when it is combined with Phenytoin.
PimecrolimusThe metabolism of Pimecrolimus can be decreased when combined with Ceritinib.
PimozideThe serum concentration of Pimozide can be increased when it is combined with Ceritinib.
PindololPindolol may increase the bradycardic activities of Ceritinib.
PiroxicamThe serum concentration of Piroxicam can be increased when it is combined with Ceritinib.
PonatinibThe serum concentration of Ponatinib can be increased when it is combined with Ceritinib.
Poractant alfaPoractant alfa may increase the bradycardic activities of Ceritinib.
PosaconazoleThe serum concentration of Ceritinib can be increased when it is combined with Posaconazole.
PranlukastThe serum concentration of Pranlukast can be increased when it is combined with Ceritinib.
PrasugrelThe serum concentration of the active metabolites of Prasugrel can be reduced when Prasugrel is used in combination with Ceritinib resulting in a loss in efficacy.
PrednicarbatePrednicarbate may increase the hyperglycemic activities of Ceritinib.
PrednisolonePrednisolone may increase the hyperglycemic activities of Ceritinib.
PrednisonePrednisone may increase the hyperglycemic activities of Ceritinib.
PrimidoneThe serum concentration of Ceritinib can be decreased when it is combined with Primidone.
PropafenonePropafenone may increase the bradycardic activities of Ceritinib.
PropranololPropranolol may increase the bradycardic activities of Ceritinib.
RamelteonThe serum concentration of Ramelteon can be increased when it is combined with Ceritinib.
RanolazineThe serum concentration of Ranolazine can be increased when it is combined with Ceritinib.
RegorafenibThe serum concentration of Regorafenib can be increased when it is combined with Ceritinib.
RepaglinideThe serum concentration of Repaglinide can be increased when it is combined with Ceritinib.
Repository corticotropinRepository corticotropin may increase the hyperglycemic activities of Ceritinib.
RetapamulinThe serum concentration of Retapamulin can be increased when it is combined with Ceritinib.
RifabutinThe serum concentration of Ceritinib can be decreased when it is combined with Rifabutin.
RifampicinThe serum concentration of Ceritinib can be decreased when it is combined with Rifampicin.
RifapentineThe serum concentration of Ceritinib can be decreased when it is combined with Rifapentine.
RilpivirineThe serum concentration of Rilpivirine can be increased when it is combined with Ceritinib.
RimexoloneRimexolone may increase the hyperglycemic activities of Ceritinib.
RitonavirThe serum concentration of Ceritinib can be increased when it is combined with Ritonavir.
RivastigmineRivastigmine may increase the bradycardic activities of Ceritinib.
RomidepsinThe serum concentration of Romidepsin can be increased when it is combined with Ceritinib.
RuxolitinibThe serum concentration of Ruxolitinib can be increased when it is combined with Ceritinib.
SalmeterolThe serum concentration of Salmeterol can be increased when it is combined with Ceritinib.
SaquinavirThe serum concentration of Ceritinib can be increased when it is combined with Saquinavir.
SaxagliptinThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Ceritinib.
SildenafilThe serum concentration of Sildenafil can be increased when it is combined with Ceritinib.
SilodosinThe serum concentration of Silodosin can be increased when it is combined with Ceritinib.
SiltuximabThe serum concentration of Ceritinib can be decreased when it is combined with Siltuximab.
SimeprevirThe serum concentration of Simeprevir can be increased when it is combined with Ceritinib.
SimvastatinThe serum concentration of Simvastatin can be increased when it is combined with Ceritinib.
SonidegibThe serum concentration of Sonidegib can be increased when it is combined with Ceritinib.
SorafenibThe serum concentration of Sorafenib can be increased when it is combined with Ceritinib.
SotalolSotalol may increase the bradycardic activities of Ceritinib.
St. John's WortThe serum concentration of Ceritinib can be decreased when it is combined with St. John's Wort.
StiripentolThe serum concentration of Ceritinib can be increased when it is combined with Stiripentol.
SufentanilSufentanil may increase the bradycardic activities of Ceritinib.
SulfadiazineThe serum concentration of Sulfadiazine can be increased when it is combined with Ceritinib.
SuvorexantThe serum concentration of Suvorexant can be increased when it is combined with Ceritinib.
TadalafilThe serum concentration of Tadalafil can be increased when it is combined with Ceritinib.
TamsulosinThe serum concentration of Tamsulosin can be increased when it is combined with Ceritinib.
TasimelteonThe serum concentration of Tasimelteon can be increased when it is combined with Ceritinib.
TelaprevirThe serum concentration of Ceritinib can be increased when it is combined with Telaprevir.
TelithromycinThe serum concentration of Ceritinib can be increased when it is combined with Telithromycin.
TerfenadineThe serum concentration of Terfenadine can be increased when it is combined with Ceritinib.
TesmilifeneThe serum concentration of Ceritinib can be decreased when it is combined with Tesmilifene.
TicagrelorThe serum concentration of the active metabolites of Ticagrelor can be reduced when Ticagrelor is used in combination with Ceritinib resulting in a loss in efficacy.
TimololTimolol may increase the bradycardic activities of Ceritinib.
TizanidineTizanidine may increase the bradycardic activities of Ceritinib.
TocilizumabThe serum concentration of Ceritinib can be decreased when it is combined with Tocilizumab.
TofacitinibThe serum concentration of Tofacitinib can be increased when it is combined with Ceritinib.
TolbutamideThe serum concentration of Tolbutamide can be increased when it is combined with Ceritinib.
TolterodineThe serum concentration of Tolterodine can be increased when it is combined with Ceritinib.
TolvaptanThe serum concentration of Tolvaptan can be increased when it is combined with Ceritinib.
TorasemideThe serum concentration of Torasemide can be increased when it is combined with Ceritinib.
ToremifeneThe risk or severity of adverse effects can be increased when Ceritinib is combined with Toremifene.
TrabectedinThe serum concentration of Trabectedin can be increased when it is combined with Ceritinib.
TramadolThe serum concentration of Tramadol can be increased when it is combined with Ceritinib.
Trastuzumab emtansineThe serum concentration of the active metabolites of ado-trastuzumab emtansine can be increased when ado-trastuzumab emtansine is used in combination with Ceritinib.
TriamcinoloneTriamcinolone may increase the hyperglycemic activities of Ceritinib.
TrimethoprimThe serum concentration of Trimethoprim can be increased when it is combined with Ceritinib.
UlipristalThe serum concentration of Ulipristal can be increased when it is combined with Ceritinib.
UlobetasolHalobetasol Propionate may increase the hyperglycemic activities of Ceritinib.
VardenafilThe serum concentration of Vardenafil can be increased when it is combined with Ceritinib.
VemurafenibThe serum concentration of Vemurafenib can be increased when it is combined with Ceritinib.
VerapamilVerapamil may increase the bradycardic activities of Ceritinib.
VilazodoneThe serum concentration of Vilazodone can be increased when it is combined with Ceritinib.
VildagliptinThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Ceritinib.
VincristineThe serum concentration of Vincristine can be increased when it is combined with Ceritinib.
VindesineThe serum concentration of Vindesine can be increased when it is combined with Ceritinib.
VorapaxarThe serum concentration of Vorapaxar can be increased when it is combined with Ceritinib.
VoriconazoleThe serum concentration of Ceritinib can be increased when it is combined with Voriconazole.
WarfarinThe serum concentration of Warfarin can be increased when it is combined with Ceritinib.
ZafirlukastThe serum concentration of Zafirlukast can be increased when it is combined with Ceritinib.
ZopicloneThe serum concentration of Zopiclone can be increased when it is combined with Ceritinib.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
antagonist
General Function:
Transmembrane receptor protein tyrosine kinase activity
Specific Function:
Neuronal orphan receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis and differentiation of the nervous system. Transduces signals from ligands at the cell surface, through specific activation of the mitogen-activated protein kinase (MAPK) pathway. Phosphorylates almost...
Gene Name:
ALK
Uniprot ID:
Q9UM73
Molecular Weight:
176440.535 Da
References
  1. Galkin AV, Melnick JS, Kim S, Hood TL, Li N, Li L, Xia G, Steensma R, Chopiuk G, Jiang J, Wan Y, Ding P, Liu Y, Sun F, Schultz PG, Gray NS, Warmuth M: Identification of NVP-TAE684, a potent, selective, and efficacious inhibitor of NPM-ALK. Proc Natl Acad Sci U S A. 2007 Jan 2;104(1):270-5. Epub 2006 Dec 21. [PubMed:17185414 ]
  2. Marsilje TH, Pei W, Chen B, Lu W, Uno T, Jin Y, Jiang T, Kim S, Li N, Warmuth M, Sarkisova Y, Sun F, Steffy A, Pferdekamper AC, Li AG, Joseph SB, Kim Y, Liu B, Tuntland T, Cui X, Gray NS, Steensma R, Wan Y, Jiang J, Chopiuk G, Li J, Gordon WP, Richmond W, Johnson K, Chang J, Groessl T, He YQ, Phimister A, Aycinena A, Lee CC, Bursulaya B, Karanewsky DS, Seidel HM, Harris JL, Michellys PY: Synthesis, structure-activity relationships, and in vivo efficacy of the novel potent and selective anaplastic lymphoma kinase (ALK) inhibitor 5-chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(2-(isopropylsulf onyl)phenyl)pyrimidine-2,4-diamine (LDK378) currently in phase 1 and phase 2 clinical trials. J Med Chem. 2013 Jul 25;56(14):5675-90. doi: 10.1021/jm400402q. Epub 2013 Jun 26. [PubMed:23742252 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
no
Actions
substrate
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular Weight:
141477.255 Da
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Drug created on May 11, 2015 16:20 / Updated on July 30, 2016 02:50