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Identification
NamePalbociclib
Accession NumberDB09073
TypeSmall Molecule
GroupsApproved
Description

Palbociclib is an oral, reversible, selective, small-molecule inhibitor of CDK4 and CDK6 indicated in combination with letrozole for the treatment of postmenopausal women with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer as initial endocrine-based therapy for their metastatic disease. CDK4 and CDK6 along with their regulatory partner cyclin D1 play a key role in regulating the G1- to S-phase cell-cycle transition via regulation of phosphorylation of the retinoblastoma (Rb) protein. Inhibition of these proteins leads to reduced phosphorylation of Rb, inhibition of downstream signalling, and increased tumor growth arrest. Palbociclib received an accelerated approval from the Food and Drug Administration on February 3, 2015.

Structure
Thumb
Synonyms
6-acetyl-8-cyclopentyl-5-methyl-2-{[5-(piperazin-1-yl)pyridin-2-yl]amino}pyrido[2,3-d]pyrimidin-7(8H)-one
External Identifiers
  • PD 0332991
  • PD 332991
  • PD-0332991
  • PD-332991
  • PD0332991
  • PD332991
  • UNII-G9ZF61LE7G
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Ibrancecapsule75 mg/1oralPfizer Laboratories Div Pfizer Inc2015-02-03Not applicableUs
Ibrancecapsule125 mgoralPfizer Canada Inc2016-04-19Not applicableCanada
Ibrancecapsule100 mgoralPfizer Canada Inc2016-04-19Not applicableCanada
Ibrancecapsule75 mgoralPfizer Canada Inc2016-04-20Not applicableCanada
Ibrancecapsule125 mg/1oralU.S. Pharmaceuticals2015-02-03Not applicableUs
Ibrancecapsule125 mg/1oralPfizer Laboratories Div Pfizer Inc2015-02-03Not applicableUs
Ibrancecapsule100 mg/1oralPfizer Laboratories Div Pfizer Inc2015-02-03Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Palbociclib Isethionate
ThumbNot applicableDBSALT001110
Categories
UNIIG9ZF61LE7G
CAS number571190-30-2
WeightAverage: 447.5328
Monoisotopic: 447.238273207
Chemical FormulaC24H29N7O2
InChI KeyAHJRHEGDXFFMBM-UHFFFAOYSA-N
InChI
InChI=1S/C24H29N7O2/c1-15-19-14-27-24(28-20-8-7-18(13-26-20)30-11-9-25-10-12-30)29-22(19)31(17-5-3-4-6-17)23(33)21(15)16(2)32/h7-8,13-14,17,25H,3-6,9-12H2,1-2H3,(H,26,27,28,29)
IUPAC Name
6-acetyl-8-cyclopentyl-5-methyl-2-{[5-(piperazin-1-yl)pyridin-2-yl]amino}-7H,8H-pyrido[2,3-d]pyrimidin-7-one
SMILES
CC(=O)C1=C(C)C2=CN=C(NC3=NC=C(C=C3)N3CCNCC3)N=C2N(C2CCCC2)C1=O
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as pyridinylpiperazines. These are compounds containing a pyridinylpiperazine skeleton, which consists of a pyridine linked (not fused) to a piperazine by a bond by a single bond that is not part of a ring.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassDiazinanes
Sub ClassPiperazines
Direct ParentPyridinylpiperazines
Alternative Parents
Substituents
  • N-arylpiperazine
  • Pyridinylpiperazine
  • Pyridopyrimidine
  • Dialkylarylamine
  • Aryl alkyl ketone
  • Aryl ketone
  • Methylpyridine
  • Pyridinone
  • Aminopyridine
  • Imidolactam
  • Pyrimidine
  • Pyridine
  • Heteroaromatic compound
  • Vinylogous amide
  • Tertiary amine
  • Lactam
  • Ketone
  • Azacycle
  • Secondary amine
  • Secondary aliphatic amine
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationPalbociclib is indicated in combination with letrozole for the treatment of postmenopausal women with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer as initial endocrine-based therapy for their metastatic disease. This indication is approved under accelerated approval based on progression-free survival (PFS). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
PharmacodynamicsTreatment of breast cancer cell lines with the combination of palbociclib and antiestrogens leads to decreased retinoblastoma protein (Rb) phosphorylation resulting in reduced E2F expression and signaling and increased growth arrest compared to treatment with each drug alone. In vitro treatment of ER-positive breast cancer cell lines with the combination of palbociclib and antiestrogens leads to increased cell senescence, which was sustained for up to 6 days following drug removal. In vivo studies using a patient-derived ER-positive breast cancer xenograft model demonstrated that the combination of palbociclib and letrozole increased the inhibition of Rb phosphorylation, downstream signaling and tumor growth compared to each drug alone.
Mechanism of actionPalbociclib is an oral, reversible, selective, small-molecule inhibitor of CDK4 and CDK6. CDK4 and CDK6 along with their regulatory partner cyclin D1 play a key role in regulating the G1- to S-phase cell-cycle transition via regulation of phosphorylation of the retinoblastoma (Rb) protein.
Related Articles
AbsorptionThe mean Cmax of palbociclib is generally observed between 6 to 12 hours (time to reach maximum concentration, Tmax) following oral administration. The mean absolute bioavailability after an oral 125 mg dose is 46%.
Volume of distribution

The mean apparent distribution of palbociclib is 2583 L, suggesting that palbociclib penetrates extensively into peripheral tissues.

Protein bindingBinding of palbociclib to human plasma proteins in vitro is approximately 85%.
Metabolism

The primary metabolic pathways for palbociclib involve oxidation and sulfonation, with acylation and glucuronidation contributing as minor pathways. Palbociclib is the major circulating drug-derived entity in plasma (23%). The major circulating metabolite was found to be a glucuronide conjugate of palbociclib, although it only represented 1.5% of the administered dose in the excreta.

Route of eliminationPalbociclib was extensively metabolized with unchanged drug accounting for 2.3% and 6.9% of radioactivity in feces and urine, respectively. In feces, the sulfamic acid conjugate of palbociclib was the major drug-related component, accounting for 26% of the administered dose.
Half lifeThe mean plasma elimination half-life is 29 hours.
Clearance

63.1 L/hr

ToxicityNot Available
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
Capsuleoral100 mg/1
Capsuleoral100 mg
Capsuleoral125 mg/1
Capsuleoral125 mg
Capsuleoral75 mg/1
Capsuleoral75 mg
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6936612 No2003-01-222023-01-22Us
US7208489 No2003-01-162023-01-16Us
US7456168 No2003-01-162023-01-16Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
pKa7.4 (the secondary piperazine nitrogen) and 3.9 (the pyridine nitrogen)FDA Label
Predicted Properties
PropertyValueSource
Water Solubility0.0174 mg/mLALOGPS
logP2.12ALOGPS
logP2.77ChemAxon
logS-4.4ALOGPS
pKa (Strongest Acidic)11.34ChemAxon
pKa (Strongest Basic)8.86ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area103.35 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity127.47 m3·mol-1ChemAxon
Polarizability49.69 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General References
  1. Dhillon S: Palbociclib: first global approval. Drugs. 2015 Apr;75(5):543-51. doi: 10.1007/s40265-015-0379-9. [PubMed:25792301 ]
  2. Fry DW, Harvey PJ, Keller PR, Elliott WL, Meade M, Trachet E, Albassam M, Zheng X, Leopold WR, Pryer NK, Toogood PL: Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts. Mol Cancer Ther. 2004 Nov;3(11):1427-38. [PubMed:15542782 ]
  3. Logan JE, Mostofizadeh N, Desai AJ, VON Euw E, Conklin D, Konkankit V, Hamidi H, Eckardt M, Anderson L, Chen HW, Ginther C, Taschereau E, Bui PH, Christensen JG, Belldegrun AS, Slamon DJ, Kabbinavar FF: PD-0332991, a potent and selective inhibitor of cyclin-dependent kinase 4/6, demonstrates inhibition of proliferation in renal cell carcinoma at nanomolar concentrations and molecular markers predict for sensitivity. Anticancer Res. 2013 Aug;33(8):2997-3004. [PubMed:23898052 ]
  4. Authors unspecified: Palbociclib Extends Survival in Advanced Breast Cancer. Cancer Discov. 2015 Jul;5(7):OF5. doi: 10.1158/2159-8290.CD-NB2015-083. Epub 2015 Jun 2. [PubMed:26036642 ]
  5. Turner NC, Ro J, Andre F, Loi S, Verma S, Iwata H, Harbeck N, Loibl S, Huang Bartlett C, Zhang K, Giorgetti C, Randolph S, Koehler M, Cristofanilli M: Palbociclib in Hormone-Receptor-Positive Advanced Breast Cancer. N Engl J Med. 2015 Jul 16;373(3):209-19. doi: 10.1056/NEJMoa1505270. Epub 2015 Jun 1. [PubMed:26030518 ]
  6. Finn RS, Crown JP, Lang I, Boer K, Bondarenko IM, Kulyk SO, Ettl J, Patel R, Pinter T, Schmidt M, Shparyk Y, Thummala AR, Voytko NL, Fowst C, Huang X, Kim ST, Randolph S, Slamon DJ: The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. Lancet Oncol. 2015 Jan;16(1):25-35. doi: 10.1016/S1470-2045(14)71159-3. Epub 2014 Dec 16. [PubMed:25524798 ]
  7. DeMichele A, Clark AS, Tan KS, Heitjan DF, Gramlich K, Gallagher M, Lal P, Feldman M, Zhang P, Colameco C, Lewis D, Langer M, Goodman N, Domchek S, Gogineni K, Rosen M, Fox K, O'Dwyer P: CDK 4/6 inhibitor palbociclib (PD0332991) in Rb+ advanced breast cancer: phase II activity, safety, and predictive biomarker assessment. Clin Cancer Res. 2015 Mar 1;21(5):995-1001. doi: 10.1158/1078-0432.CCR-14-2258. Epub 2014 Dec 11. [PubMed:25501126 ]
External Links
ATC CodesL01XE33
AHFS Codes
  • 10:00
PDB EntriesNot Available
FDA labelDownload (481 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AlfentanilThe serum concentration of Alfentanil can be increased when it is combined with Palbociclib.
AlfuzosinThe serum concentration of Alfuzosin can be increased when it is combined with Palbociclib.
AlitretinoinThe serum concentration of Alitretinoin can be increased when it is combined with Palbociclib.
AlprazolamThe serum concentration of Alprazolam can be increased when it is combined with Palbociclib.
AminophyllineThe serum concentration of Aminophylline can be increased when it is combined with Palbociclib.
AmiodaroneThe serum concentration of Amiodarone can be increased when it is combined with Palbociclib.
AmlodipineThe serum concentration of Amlodipine can be increased when it is combined with Palbociclib.
AprepitantThe serum concentration of Aprepitant can be increased when it is combined with Palbociclib.
AripiprazoleThe serum concentration of Aripiprazole can be increased when it is combined with Palbociclib.
ArmodafinilThe serum concentration of Armodafinil can be increased when it is combined with Palbociclib.
AtazanavirThe serum concentration of Palbociclib can be increased when it is combined with Atazanavir.
AtorvastatinThe serum concentration of Atorvastatin can be increased when it is combined with Palbociclib.
AvanafilThe serum concentration of Avanafil can be increased when it is combined with Palbociclib.
AxitinibThe serum concentration of Axitinib can be increased when it is combined with Palbociclib.
BenzphetamineThe serum concentration of Benzphetamine can be increased when it is combined with Palbociclib.
BexaroteneThe serum concentration of Palbociclib can be decreased when it is combined with Bexarotene.
BisoprololThe serum concentration of Bisoprolol can be increased when it is combined with Palbociclib.
BoceprevirThe serum concentration of Palbociclib can be increased when it is combined with Boceprevir.
BosentanThe serum concentration of Palbociclib can be decreased when it is combined with Bosentan.
BosutinibThe serum concentration of Bosutinib can be increased when it is combined with Palbociclib.
BrexpiprazoleThe serum concentration of Brexpiprazole can be increased when it is combined with Palbociclib.
BromocriptineThe serum concentration of Bromocriptine can be increased when it is combined with Palbociclib.
BudesonideThe serum concentration of Budesonide can be increased when it is combined with Palbociclib.
BuprenorphineThe serum concentration of Buprenorphine can be increased when it is combined with Palbociclib.
BuspironeThe serum concentration of Buspirone can be increased when it is combined with Palbociclib.
CabazitaxelThe serum concentration of Cabazitaxel can be increased when it is combined with Palbociclib.
CabozantinibThe serum concentration of Cabozantinib can be increased when it is combined with Palbociclib.
CalcitriolThe serum concentration of Calcitriol can be increased when it is combined with Palbociclib.
CarbamazepineThe serum concentration of Palbociclib can be decreased when it is combined with Carbamazepine.
CeritinibThe serum concentration of Palbociclib can be increased when it is combined with Ceritinib.
ChlordiazepoxideThe serum concentration of Chlordiazepoxide can be increased when it is combined with Palbociclib.
ChloroquineThe serum concentration of Chloroquine can be increased when it is combined with Palbociclib.
CilostazolThe serum concentration of Cilostazol can be increased when it is combined with Palbociclib.
CinacalcetThe serum concentration of Cinacalcet can be increased when it is combined with Palbociclib.
CisaprideThe serum concentration of Cisapride can be increased when it is combined with Palbociclib.
CitalopramThe serum concentration of Citalopram can be increased when it is combined with Palbociclib.
ClarithromycinThe serum concentration of Palbociclib can be increased when it is combined with Clarithromycin.
ClonazepamThe serum concentration of Clonazepam can be increased when it is combined with Palbociclib.
ClorazepateThe serum concentration of Clorazepate can be increased when it is combined with Palbociclib.
ClozapineThe risk or severity of adverse effects can be increased when Palbociclib is combined with Clozapine.
CobicistatThe serum concentration of Palbociclib can be increased when it is combined with Cobicistat.
CobimetinibThe serum concentration of Cobimetinib can be increased when it is combined with Palbociclib.
CocaineThe serum concentration of Cocaine can be increased when it is combined with Palbociclib.
ColchicineThe serum concentration of Colchicine can be increased when it is combined with Palbociclib.
ConivaptanThe serum concentration of Palbociclib can be increased when it is combined with Conivaptan.
CrizotinibThe serum concentration of Crizotinib can be increased when it is combined with Palbociclib.
CyclosporineThe serum concentration of Cyclosporine can be increased when it is combined with Palbociclib.
Cyproterone acetateThe serum concentration of Cyproterone acetate can be increased when it is combined with Palbociclib.
DabrafenibThe serum concentration of Palbociclib can be decreased when it is combined with Dabrafenib.
DaclatasvirThe serum concentration of Daclatasvir can be increased when it is combined with Palbociclib.
DantroleneThe serum concentration of Dantrolene can be increased when it is combined with Palbociclib.
DapsoneThe serum concentration of Dapsone can be increased when it is combined with Palbociclib.
DarifenacinThe serum concentration of Darifenacin can be increased when it is combined with Palbociclib.
DarunavirThe serum concentration of Palbociclib can be increased when it is combined with Darunavir.
DasatinibThe serum concentration of Dasatinib can be increased when it is combined with Palbociclib.
DeferasiroxThe serum concentration of Palbociclib can be decreased when it is combined with Deferasirox.
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Palbociclib.
DexamethasoneThe serum concentration of Palbociclib can be decreased when it is combined with Dexamethasone.
DiazepamThe serum concentration of Diazepam can be increased when it is combined with Palbociclib.
DihydroergotamineThe serum concentration of Dihydroergotamine can be increased when it is combined with Palbociclib.
DiltiazemThe serum concentration of Diltiazem can be increased when it is combined with Palbociclib.
DisopyramideThe serum concentration of Disopyramide can be increased when it is combined with Palbociclib.
DocetaxelThe serum concentration of Docetaxel can be increased when it is combined with Palbociclib.
DofetilideThe serum concentration of Dofetilide can be increased when it is combined with Palbociclib.
DomperidoneThe serum concentration of Domperidone can be increased when it is combined with Palbociclib.
DoxazosinThe serum concentration of Doxazosin can be increased when it is combined with Palbociclib.
DoxorubicinThe serum concentration of Doxorubicin can be increased when it is combined with Palbociclib.
DronedaroneThe serum concentration of Dronedarone can be increased when it is combined with Palbociclib.
EfavirenzThe serum concentration of Palbociclib can be decreased when it is combined with Efavirenz.
EletriptanThe serum concentration of Eletriptan can be increased when it is combined with Palbociclib.
EliglustatThe serum concentration of Eliglustat can be increased when it is combined with Palbociclib.
EnzalutamideThe serum concentration of Palbociclib can be decreased when it is combined with Enzalutamide.
EplerenoneThe serum concentration of Eplerenone can be increased when it is combined with Palbociclib.
Ergoloid mesylateThe serum concentration of Ergoloid mesylate can be increased when it is combined with Palbociclib.
ErgonovineThe serum concentration of Ergonovine can be increased when it is combined with Palbociclib.
ErgotamineThe serum concentration of Ergotamine can be increased when it is combined with Palbociclib.
ErlotinibThe serum concentration of Erlotinib can be increased when it is combined with Palbociclib.
ErythromycinThe serum concentration of Erythromycin can be increased when it is combined with Palbociclib.
EscitalopramThe serum concentration of Escitalopram can be increased when it is combined with Palbociclib.
Eslicarbazepine acetateThe serum concentration of Palbociclib can be decreased when it is combined with Eslicarbazepine acetate.
EszopicloneThe serum concentration of Eszopiclone can be increased when it is combined with Palbociclib.
EthosuximideThe serum concentration of Ethosuximide can be increased when it is combined with Palbociclib.
EtoposideThe serum concentration of Etoposide can be increased when it is combined with Palbociclib.
EtravirineThe serum concentration of Palbociclib can be decreased when it is combined with Etravirine.
EverolimusThe serum concentration of Everolimus can be increased when it is combined with Palbociclib.
FelbamateThe serum concentration of Felbamate can be increased when it is combined with Palbociclib.
FelodipineThe serum concentration of Felodipine can be increased when it is combined with Palbociclib.
FentanylThe serum concentration of Fentanyl can be increased when it is combined with Palbociclib.
FesoterodineThe serum concentration of Fesoterodine can be increased when it is combined with Palbociclib.
FlibanserinThe serum concentration of Flibanserin can be increased when it is combined with Palbociclib.
FluconazoleThe metabolism of Palbociclib can be decreased when combined with Fluconazole.
FlunisolideThe serum concentration of Flunisolide can be increased when it is combined with Palbociclib.
FlurazepamThe serum concentration of Flurazepam can be increased when it is combined with Palbociclib.
FlutamideThe serum concentration of Flutamide can be increased when it is combined with Palbociclib.
FosaprepitantThe serum concentration of Fosaprepitant can be increased when it is combined with Palbociclib.
FosphenytoinThe serum concentration of Palbociclib can be decreased when it is combined with Fosphenytoin.
Fusidic AcidThe serum concentration of Palbociclib can be increased when it is combined with Fusidic Acid.
GefitinibThe serum concentration of Gefitinib can be increased when it is combined with Palbociclib.
GuanfacineThe serum concentration of Guanfacine can be increased when it is combined with Palbociclib.
HaloperidolThe serum concentration of Haloperidol can be increased when it is combined with Palbociclib.
HydrocodoneThe serum concentration of Hydrocodone can be increased when it is combined with Palbociclib.
Hydroxyprogesterone caproateThe serum concentration of Hydroxyprogesterone caproate can be increased when it is combined with Palbociclib.
IbrutinibThe serum concentration of Ibrutinib can be increased when it is combined with Palbociclib.
IdelalisibThe serum concentration of Palbociclib can be increased when it is combined with Idelalisib.
IndinavirThe serum concentration of Palbociclib can be increased when it is combined with Indinavir.
IrinotecanThe serum concentration of Irinotecan can be increased when it is combined with Palbociclib.
IsavuconazoniumThe serum concentration of Isavuconazonium can be increased when it is combined with Palbociclib.
IsosorbideThe serum concentration of Isosorbide can be increased when it is combined with Palbociclib.
Isosorbide DinitrateThe serum concentration of Isosorbide Dinitrate can be increased when it is combined with Palbociclib.
Isosorbide MononitrateThe serum concentration of Isosorbide Mononitrate can be increased when it is combined with Palbociclib.
IsradipineThe serum concentration of Isradipine can be increased when it is combined with Palbociclib.
ItraconazoleThe serum concentration of Palbociclib can be increased when it is combined with Itraconazole.
IvabradineThe serum concentration of Ivabradine can be increased when it is combined with Palbociclib.
IvacaftorThe serum concentration of Ivacaftor can be increased when it is combined with Palbociclib.
IxabepiloneThe serum concentration of Ixabepilone can be increased when it is combined with Palbociclib.
KetamineThe serum concentration of Ketamine can be increased when it is combined with Palbociclib.
KetoconazoleThe serum concentration of Palbociclib can be increased when it is combined with Ketoconazole.
LapatinibThe serum concentration of Lapatinib can be increased when it is combined with Palbociclib.
LeflunomideThe risk or severity of adverse effects can be increased when Palbociclib is combined with Leflunomide.
LevomilnacipranThe serum concentration of Levomilnacipran can be increased when it is combined with Palbociclib.
LidocaineThe serum concentration of Lidocaine can be increased when it is combined with Palbociclib.
LomitapideThe serum concentration of Lomitapide can be increased when it is combined with Palbociclib.
LovastatinThe serum concentration of Lovastatin can be increased when it is combined with Palbociclib.
LuliconazoleThe serum concentration of Palbociclib can be increased when it is combined with Luliconazole.
LurasidoneThe serum concentration of Lurasidone can be increased when it is combined with Palbociclib.
MacitentanThe serum concentration of MACITENTAN can be increased when it is combined with Palbociclib.
MaravirocThe serum concentration of Maraviroc can be increased when it is combined with Palbociclib.
MefloquineThe serum concentration of Mefloquine can be increased when it is combined with Palbociclib.
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Palbociclib.
MethadoneThe serum concentration of Methadone can be increased when it is combined with Palbociclib.
MidazolamThe serum concentration of Midazolam can be increased when it is combined with Palbociclib.
MifepristoneThe serum concentration of Palbociclib can be increased when it is combined with Mifepristone.
MirtazapineThe serum concentration of Mirtazapine can be increased when it is combined with Palbociclib.
MitotaneThe serum concentration of Palbociclib can be decreased when it is combined with Mitotane.
ModafinilThe serum concentration of Palbociclib can be decreased when it is combined with Modafinil.
NafcillinThe serum concentration of Palbociclib can be decreased when it is combined with Nafcillin.
NaloxegolThe serum concentration of Naloxegol can be increased when it is combined with Palbociclib.
NatalizumabThe risk or severity of adverse effects can be increased when Palbociclib is combined with Natalizumab.
NateglinideThe serum concentration of Nateglinide can be increased when it is combined with Palbociclib.
NefazodoneThe serum concentration of Palbociclib can be increased when it is combined with Nefazodone.
NelfinavirThe serum concentration of Palbociclib can be increased when it is combined with Nelfinavir.
NetupitantThe serum concentration of Palbociclib can be increased when it is combined with Netupitant.
NicardipineThe serum concentration of Nicardipine can be increased when it is combined with Palbociclib.
NifedipineThe serum concentration of Nifedipine can be increased when it is combined with Palbociclib.
NilotinibThe serum concentration of Nilotinib can be increased when it is combined with Palbociclib.
NimodipineThe serum concentration of Nimodipine can be increased when it is combined with Palbociclib.
NisoldipineThe serum concentration of Nisoldipine can be increased when it is combined with Palbociclib.
OlaparibThe serum concentration of Olaparib can be increased when it is combined with Palbociclib.
OxycodoneThe serum concentration of Oxycodone can be increased when it is combined with Palbociclib.
PaclitaxelThe serum concentration of Paclitaxel can be increased when it is combined with Palbociclib.
PanobinostatThe serum concentration of Panobinostat can be increased when it is combined with Palbociclib.
PazopanibThe serum concentration of Pazopanib can be increased when it is combined with Palbociclib.
PhenobarbitalThe serum concentration of Palbociclib can be decreased when it is combined with Phenobarbital.
PhenytoinThe serum concentration of Palbociclib can be decreased when it is combined with Phenytoin.
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Palbociclib.
PimozideThe serum concentration of Pimozide can be increased when it is combined with Palbociclib.
PipotiazineThe serum concentration of Pipotiazine can be increased when it is combined with Palbociclib.
PosaconazoleThe serum concentration of Palbociclib can be increased when it is combined with Posaconazole.
PraziquantelThe serum concentration of Praziquantel can be increased when it is combined with Palbociclib.
PrimidoneThe serum concentration of Palbociclib can be decreased when it is combined with Primidone.
QuetiapineThe serum concentration of Quetiapine can be increased when it is combined with Palbociclib.
QuinidineThe serum concentration of Quinidine can be increased when it is combined with Palbociclib.
QuinineThe serum concentration of Quinine can be increased when it is combined with Palbociclib.
RanolazineThe serum concentration of Ranolazine can be increased when it is combined with Palbociclib.
RegorafenibThe serum concentration of Regorafenib can be increased when it is combined with Palbociclib.
RifabutinThe serum concentration of Palbociclib can be decreased when it is combined with Rifabutin.
RifampicinThe serum concentration of Palbociclib can be decreased when it is combined with Rifampicin.
RifapentineThe serum concentration of Palbociclib can be decreased when it is combined with Rifapentine.
RitonavirThe serum concentration of Palbociclib can be increased when it is combined with Ritonavir.
RoflumilastRoflumilast may increase the immunosuppressive activities of Palbociclib.
RuxolitinibThe serum concentration of Ruxolitinib can be increased when it is combined with Palbociclib.
SalmeterolThe serum concentration of Salmeterol can be increased when it is combined with Palbociclib.
SaquinavirThe serum concentration of Palbociclib can be increased when it is combined with Saquinavir.
SaxagliptinThe serum concentration of Saxagliptin can be increased when it is combined with Palbociclib.
SildenafilThe serum concentration of Sildenafil can be increased when it is combined with Palbociclib.
SilodosinThe serum concentration of Silodosin can be increased when it is combined with Palbociclib.
SiltuximabThe serum concentration of Palbociclib can be decreased when it is combined with Siltuximab.
SimeprevirThe serum concentration of Simeprevir can be increased when it is combined with Palbociclib.
SimvastatinThe serum concentration of Simvastatin can be increased when it is combined with Palbociclib.
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Palbociclib.
SirolimusThe serum concentration of Sirolimus can be increased when it is combined with Palbociclib.
SolifenacinThe serum concentration of Solifenacin can be increased when it is combined with Palbociclib.
SonidegibThe serum concentration of Sonidegib can be increased when it is combined with Palbociclib.
SpiramycinThe serum concentration of Spiramycin can be increased when it is combined with Palbociclib.
StiripentolThe serum concentration of Palbociclib can be increased when it is combined with Stiripentol.
SufentanilThe serum concentration of Sufentanil can be increased when it is combined with Palbociclib.
SunitinibThe serum concentration of Sunitinib can be increased when it is combined with Palbociclib.
SuvorexantThe serum concentration of Suvorexant can be increased when it is combined with Palbociclib.
TacrolimusThe serum concentration of Tacrolimus can be increased when it is combined with Palbociclib.
TadalafilThe serum concentration of Tadalafil can be increased when it is combined with Palbociclib.
TamoxifenThe serum concentration of Tamoxifen can be increased when it is combined with Palbociclib.
TamsulosinThe serum concentration of Tamsulosin can be increased when it is combined with Palbociclib.
TelaprevirThe serum concentration of Palbociclib can be increased when it is combined with Telaprevir.
TelithromycinThe serum concentration of Palbociclib can be increased when it is combined with Telithromycin.
TemsirolimusThe serum concentration of Temsirolimus can be increased when it is combined with Palbociclib.
TeniposideThe serum concentration of Teniposide can be increased when it is combined with Palbociclib.
TheophyllineThe serum concentration of Theophylline can be increased when it is combined with Palbociclib.
TiagabineThe serum concentration of Tiagabine can be increased when it is combined with Palbociclib.
TocilizumabThe serum concentration of Palbociclib can be decreased when it is combined with Tocilizumab.
TofacitinibPalbociclib may increase the immunosuppressive activities of Tofacitinib.
TolterodineThe serum concentration of Tolterodine can be increased when it is combined with Palbociclib.
TolvaptanThe serum concentration of Tolvaptan can be increased when it is combined with Palbociclib.
TrabectedinThe serum concentration of Trabectedin can be increased when it is combined with Palbociclib.
TrastuzumabTrastuzumab may increase the neutropenic activities of Palbociclib.
Trastuzumab emtansineThe serum concentration of ado-trastuzumab emtansine can be increased when it is combined with Palbociclib.
TrazodoneThe serum concentration of Trazodone can be increased when it is combined with Palbociclib.
TriazolamThe serum concentration of Triazolam can be increased when it is combined with Palbociclib.
TrimipramineThe serum concentration of Trimipramine can be increased when it is combined with Palbociclib.
VardenafilThe serum concentration of Vardenafil can be increased when it is combined with Palbociclib.
VemurafenibThe serum concentration of Vemurafenib can be increased when it is combined with Palbociclib.
VenlafaxineThe serum concentration of Venlafaxine can be increased when it is combined with Palbociclib.
VerapamilThe serum concentration of Verapamil can be increased when it is combined with Palbociclib.
VinblastineThe serum concentration of Vinblastine can be increased when it is combined with Palbociclib.
VincristineThe serum concentration of Vincristine can be increased when it is combined with Palbociclib.
VinorelbineThe serum concentration of Vinorelbine can be increased when it is combined with Palbociclib.
VoriconazoleThe serum concentration of Palbociclib can be increased when it is combined with Voriconazole.
ZolpidemThe serum concentration of Zolpidem can be increased when it is combined with Palbociclib.
ZonisamideThe serum concentration of Zonisamide can be increased when it is combined with Palbociclib.
ZopicloneThe serum concentration of Zopiclone can be increased when it is combined with Palbociclib.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
Inhibitor
General Function:
Cyclin-dependent protein serine/threonine kinase regulator activity
Specific Function:
Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G(1)/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complexes and the subsequent transcription of E2F target genes which are responsible for the progres...
Gene Name:
CDK4
Uniprot ID:
P11802
Molecular Weight:
33729.55 Da
References
  1. Fry DW, Harvey PJ, Keller PR, Elliott WL, Meade M, Trachet E, Albassam M, Zheng X, Leopold WR, Pryer NK, Toogood PL: Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts. Mol Cancer Ther. 2004 Nov;3(11):1427-38. [PubMed:15542782 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
Inhibitor
General Function:
Cyclin-dependent protein serine/threonine kinase activity
Specific Function:
Serine/threonine-protein kinase involved in the control of the cell cycle and differentiation; promotes G1/S transition. Phosphorylates pRB/RB1 and NPM1. Interacts with D-type G1 cyclins during interphase at G1 to form a pRB/RB1 kinase and controls the entrance into the cell cycle. Involved in initiation and maintenance of cell cycle exit during cell differentiation; prevents cell proliferation...
Gene Name:
CDK6
Uniprot ID:
Q00534
Molecular Weight:
36938.025 Da
References
  1. Fry DW, Harvey PJ, Keller PR, Elliott WL, Meade M, Trachet E, Albassam M, Zheng X, Leopold WR, Pryer NK, Toogood PL: Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts. Mol Cancer Ther. 2004 Nov;3(11):1427-38. [PubMed:15542782 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
no
Actions
substrate
General Function:
Vitamin d3 25-hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
2. Sulfotransferase 2A1
Kind
Protein
Organism
Human
Pharmacological action
no
Actions
substrate
Comments
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Drug created on May 14, 2015 14:03 / Updated on July 23, 2016 01:55