Details of the Drug

General Information of Drug (ID: DMD7L94)

Drug Name
Palbociclib
Synonyms
571190-30-2; PD0332991; PD-0332991; Ibrance; PD 0332991; UNII-G9ZF61LE7G; Palbociclib(PD0332991); 6-Acetyl-8-cyclopentyl-5-methyl-2-[[5-(piperazin-1-yl)pyridin-2-yl]amino]-8H-pyrido[2,3-d]pyrimidin-7-one; 6-acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one; G9ZF61LE7G; PD 332991; 6-ACETYL-8-CYCLOPENTYL-5-METHYL-2-[(5-PIPERAZIN-1-YLPYRIDIN-2-YL)AMINO]PYRIDO[2,3-D]PYRIMIDIN-7(8H)-ONE; LQQ; PD 332991, PD 0332991, PD0332991; 6-Acetyl-8-cyclopentyl-5-methyl-2-(5-piperazin-1-ylpyridin-2-ylamino)-8H-pyrido(2,3-d)pyrimidin-7-one; 6-acetyl-8-cyclopentyl-5-methyl-2-[(5-piperazin-1-ylpyridin-2-yl)amino]pyrido[2,3-d]pyrimidin-7-one; HMR-2934
Indication
Disease Entry ICD 11 Status REF
Breast cancer 2C60-2C65 Approved [1]
Solid tumour/cancer 2A00-2F9Z Phase 2 [2]
Schizophrenia 6A20 Terminated [3]
Therapeutic Class
Anticancer Agents
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 447.5
Logarithm of the Partition Coefficient (xlogp) 1.8
Rotatable Bond Count (rotbonds) 5
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 8
ADMET Property
Absorption AUC
The area under the plot of plasma concentration (AUC) of drug is 29.4 +/- 14.2 mcgh/L [4]
Absorption Cmax
The maximum plasma concentration (Cmax) of drug is 9.6 mcg/L [4]
Absorption Tmax
The time to maximum plasma concentration (Tmax) is 0.5 h [4]
Bioavailability
The bioavailability of drug is 14-15% [4]
Clearance
The apparent oral clearance of drug is 63.1 L/h [5]
Elimination
The main route of elimination of palbociclib is through feces after hepatic metabolism while renal clearance seems to play a minor role accounting only for 17.5% of the eliminated dose [5]
Half-life
The concentration or amount of drug in body reduced by one-half in 29 hours [5]
Metabolism
The drug is metabolized via the hepatic [5]
Vd
The volume of distribution (Vd) of drug is 2583 L [6]
Chemical Identifiers
Formula
C24H29N7O2
IUPAC Name
6-acetyl-8-cyclopentyl-5-methyl-2-[(5-piperazin-1-ylpyridin-2-yl)amino]pyrido[2,3-d]pyrimidin-7-one
Canonical SMILES
CC1=C(C(=O)N(C2=NC(=NC=C12)NC3=NC=C(C=C3)N4CCNCC4)C5CCCC5)C(=O)C
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)
InChIKey
AHJRHEGDXFFMBM-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
5330286
ChEBI ID
CHEBI:85993
CAS Number
571190-30-2
DrugBank ID
DB09073
TTD ID
D00UZR
VARIDT ID
DR01288
INTEDE ID
DR1229
ACDINA ID
D00504
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Cyclin-dependent kinase 4 (CDK4) TT0PG8F CDK4_HUMAN Modulator [1]
Cyclin-dependent kinase 6 (CDK6) TTO0FDJ CDK6_HUMAN Modulator [1]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [7]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [7]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4)
Main DME 		DE4LYSA CP3A4_HUMAN Substrate [8]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Alanine aminotransferase 1 (GPT) OTOXOA0Q ALAT1_HUMAN Protein Interaction/Cellular Processes [9]
Anillin (ANLN) OTXJY54C ANLN_HUMAN Gene/Protein Processing [10]
Apolipoprotein E (APOE) OTFOWL2H APOE_HUMAN Gene/Protein Processing [11]
Aurora kinase A (AURKA) OTMX0HYT AURKA_HUMAN Gene/Protein Processing [10]
Aurora kinase B (AURKB) OTIY4VHU AURKB_HUMAN Gene/Protein Processing [10]
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Gene/Protein Processing [10]
Borealin (CDCA8) OT17D55D BOREA_HUMAN Gene/Protein Processing [10]
BRCA1-associated RING domain protein 1 (BARD1) OTTC0Z9Y BARD1_HUMAN Gene/Protein Processing [10]
Cadherin-1 (CDH1) OTFJMXPM CADH1_HUMAN Protein Interaction/Cellular Processes [10]
Cadherin-2 (CDH2) OTH0Y56P CADH2_HUMAN Gene/Protein Processing [10]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Breast cancer
ICD Disease Classification 2C60-2C65
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Cyclin-dependent kinase 4 (CDK4) DTT CDK4 3.30E-72 0.65 2.39
P-glycoprotein 1 (ABCB1) DTP P-GP 3.12E-33 -8.30E-01 -1.04E+00
Breast cancer resistance protein (ABCG2) DTP BCRP 3.87E-47 -1.28E+00 -1.63E+00
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 5.59E-39 -3.76E-01 -1.64E+00
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Palbociclib
DDI Drug Name DDI Drug ID Severity Mechanism Disease REF
Talazoparib DM1KS78 Moderate Decreased clearance of Palbociclib due to the transporter inhibition by Talazoparib. Breast cancer [2C60-2C6Y] [12]
LY2835219 DM93VBZ Moderate Decreased metabolism of Palbociclib caused by LY2835219 mediated inhibition of CYP450 enzyme. Breast cancer [2C60-2C6Y] [13]
Tucatinib DMBESUA Major Decreased metabolism of Palbociclib caused by Tucatinib mediated inhibition of CYP450 enzyme. Breast cancer [2C60-2C6Y] [14]
Coadministration of a Drug Treating the Disease Different from Palbociclib (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Ivosidenib DM8S6T7 Moderate Increased metabolism of Palbociclib caused by Ivosidenib mediated induction of CYP450 enzyme. Acute myeloid leukaemia [2A60] [15]
Arn-509 DMT81LZ Major Increased metabolism of Palbociclib caused by Arn-509 mediated induction of CYP450 enzyme. Acute myeloid leukaemia [2A60] [15]
Gilteritinib DMTI0ZO Moderate Decreased metabolism of Palbociclib caused by Gilteritinib mediated inhibition of CYP450 enzyme. Acute myeloid leukaemia [2A60] [16]
Oliceridine DM6MDCF Moderate Decreased metabolism of Palbociclib caused by Oliceridine mediated inhibition of CYP450 enzyme. Acute pain [MG31] [14]
Ivabradine DM0L594 Moderate Decreased metabolism of Palbociclib caused by Ivabradine mediated inhibition of CYP450 enzyme. Angina pectoris [BA40] [16]
Troleandomycin DMUZNIG Major Decreased metabolism of Palbociclib caused by Troleandomycin mediated inhibition of CYP450 enzyme. Bacterial infection [1A00-1C4Z] [14]
Pexidartinib DMS2J0Z Moderate Increased metabolism of Palbociclib caused by Pexidartinib mediated induction of CYP450 enzyme. Bone/articular cartilage neoplasm [2F7B] [15]
PF-04449913 DMSB068 Moderate Decreased metabolism of Palbociclib caused by PF-04449913 mediated inhibition of CYP450 enzyme. Chronic myelomonocytic leukaemia [2A40] [17]
Osilodrostat DMIJC9X Moderate Decreased metabolism of Palbociclib caused by Osilodrostat mediated inhibition of CYP450 enzyme. Cushing syndrome [5A70] [16]
MK-8228 DMOB58Q Moderate Decreased metabolism of Palbociclib caused by MK-8228 mediated inhibition of CYP450 enzyme. Cytomegaloviral disease [1D82] [16]
Polatuzumab vedotin DMF6Y0L Moderate Decreased metabolism of Palbociclib caused by Polatuzumab vedotin mediated inhibition of CYP450 enzyme. Diffuse large B-cell lymphoma [2A81] [18]
Eslicarbazepine DMZREFQ Moderate Increased metabolism of Palbociclib caused by Eslicarbazepine mediated induction of CYP450 enzyme. Epilepsy/seizure [8A61-8A6Z] [15]
Tazemetostat DMWP1BH Moderate Increased metabolism of Palbociclib caused by Tazemetostat mediated induction of CYP450 enzyme. Follicular lymphoma [2A80] [19]
Avapritinib DMK2GZX Moderate Decreased metabolism of Palbociclib caused by Avapritinib mediated inhibition of CYP450 enzyme. Gastrointestinal stromal tumour [2B5B] [16]
MK-1439 DM215WE Minor Decreased metabolism of Palbociclib caused by MK-1439 mediated inhibition of CYP450 enzyme. Human immunodeficiency virus disease [1C60-1C62] [20]
Berotralstat DMWA2DZ Major Decreased clearance of Palbociclib due to the transporter inhibition by Berotralstat. Innate/adaptive immunodeficiency [4A00] [21]
Pemigatinib DM819JF Moderate Decreased metabolism of Palbociclib caused by Pemigatinib mediated inhibition of CYP450 enzyme. Liver cancer [2C12] [16]
Brigatinib DM7W94S Moderate Decreased metabolism of Palbociclib caused by Brigatinib mediated inhibition of CYP450 enzyme. Lung cancer [2C25] [15]
Lurbinectedin DMEFRTZ Moderate Decreased metabolism of Palbociclib caused by Lurbinectedin mediated inhibition of CYP450 enzyme. Lung cancer [2C25] [22]
PF-06463922 DMKM7EW Moderate Increased metabolism of Palbociclib caused by PF-06463922 mediated induction of CYP450 enzyme. Lung cancer [2C25] [15]
Osimertinib DMRJLAT Moderate Decreased metabolism of Palbociclib caused by Osimertinib mediated inhibition of CYP450 enzyme. Lung cancer [2C25] [23]
Pralsetinib DMWU0I2 Moderate Decreased metabolism of Palbociclib caused by Pralsetinib mediated inhibition of CYP450 enzyme. Lung cancer [2C25] [24]
Selpercatinib DMZR15V Moderate Decreased metabolism of Palbociclib caused by Selpercatinib mediated inhibition of CYP450 enzyme. Lung cancer [2C25] [16]
GDC-0199 DMH0QKA Moderate Decreased metabolism of Palbociclib caused by GDC-0199 mediated inhibition of CYP450 enzyme. Mature B-cell leukaemia [2A82] [15]
IPI-145 DMWA24P Moderate Decreased metabolism of Palbociclib caused by IPI-145 mediated inhibition of CYP450 enzyme. Mature B-cell leukaemia [2A82] [25]
Acalabrutinib DM7GCVW Moderate Decreased metabolism of Palbociclib caused by Acalabrutinib mediated inhibition of CYP450 enzyme. Mature B-cell lymphoma [2A85] [26]
Arry-162 DM1P6FR Moderate Decreased clearance of Palbociclib due to the transporter inhibition by Arry-162. Melanoma [2C30] [15]
Selumetinib DMC7W6R Moderate Decreased metabolism of Palbociclib caused by Selumetinib mediated inhibition of CYP450 enzyme. Melanoma [2C30] [27]
Ubrogepant DM749I3 Moderate Decreased metabolism of Palbociclib caused by Ubrogepant mediated inhibition of CYP450 enzyme. Migraine [8A80] [28]
Rimegepant DMHOAUG Moderate Decreased clearance of Palbociclib due to the transporter inhibition by Rimegepant. Migraine [8A80] [29]
Siponimod DM2R86O Major Additive immunosuppressive effects by the combination of Palbociclib and Siponimod. Multiple sclerosis [8A40] [15]
Ocrelizumab DMEZ2KH Moderate Additive immunosuppressive effects by the combination of Palbociclib and Ocrelizumab. Multiple sclerosis [8A40] [30]
Fedratinib DM4ZBK6 Moderate Decreased metabolism of Palbociclib caused by Fedratinib mediated inhibition of CYP450 enzyme. Myeloproliferative neoplasm [2A20] [16]
Rucaparib DM9PVX8 Moderate Decreased metabolism of Palbociclib caused by Rucaparib mediated inhibition of CYP450 enzyme. Ovarian cancer [2C73] [16]
Abametapir DM2RX0I Moderate Decreased metabolism of Palbociclib caused by Abametapir mediated inhibition of CYP450 enzyme. Pediculosis [1G00] [31]
Lefamulin DME6G97 Moderate Decreased metabolism of Palbociclib caused by Lefamulin mediated inhibition of CYP450 enzyme. Pneumonia [CA40] [32]
Anthrax vaccine DM9GSWY Moderate Antagonize the effect of Palbociclib when combined with Anthrax vaccine. Sepsis [1G40-1G41] [33]
Voxelotor DMCS6M5 Moderate Decreased metabolism of Palbociclib caused by Voxelotor mediated inhibition of CYP450 enzyme. Sickle-cell disorder [3A51] [16]
LDE225 DMM9F25 Moderate Decreased metabolism of Palbociclib caused by LDE225 mediated inhibition of CYP450 enzyme. Skin cancer [2C30-2C37] [34]
Telotristat ethyl DMDIYFZ Moderate Increased metabolism of Palbociclib caused by Telotristat ethyl mediated induction of CYP450 enzyme. Small intestine developmental anomaly [DA90] [16]
Larotrectinib DM26CQR Moderate Decreased clearance of Palbociclib due to the transporter inhibition by Larotrectinib. Solid tumour/cancer [2A00-2F9Z] [15]
LEE011 DMMX75K Moderate Decreased metabolism of Palbociclib caused by LEE011 mediated inhibition of CYP450 enzyme. Solid tumour/cancer [2A00-2F9Z] [16]
Lusutrombopag DMH6IKO Moderate Decreased clearance of Palbociclib due to the transporter inhibition by Lusutrombopag. Thrombocytopenia [3B64] [35]
Elagolix DMB2C0E Moderate Increased metabolism of Palbociclib caused by Elagolix mediated induction of CYP450 enzyme. Uterine fibroid [2E86] [15]
⏷ Show the Full List of 44 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG
DIG Name DIG ID PubChem CID Functional Classification
Ammonia E00007 222 Alkalizing agent
Eisenoxyd E00585 56841934 Colorant
Ferric hydroxide oxide yellow E00539 23320441 Colorant
Lactose monohydrate E00393 104938 Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate E00208 11177 lubricant
Propylene glycol E00040 1030 Antimicrobial preservative; Humectant; Plasticizing agent; Solvent
Silicon dioxide E00670 Not Available Anticaking agent; Opacifying agent; Viscosity-controlling agent
Titanium dioxide E00322 26042 Coating agent; Colorant; Opacifying agent
⏷ Show the Full List of 8 Pharmaceutical Excipients of This Drug
Pharmaceutical Formulation
Formulation Name Drug Dosage Dosage Form Route
Palbociclib 100 mg capsule 100 mg Oral Capsule Oral
Palbociclib 125 mg capsule 125 mg Oral Capsule Oral
Palbociclib 75 mg capsule 75 mg Oral Capsule Oral
Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2017
2 ClinicalTrials.gov (NCT01723774) PD 0332991 and Anastrozole for Stage 2 or 3 Estrogen Receptor Positive and HER2 Negative Breast Cancer. U.S. National Institutes of Health.
3 The pipeline and future of drug development in schizophrenia. Mol Psychiatry. 2007 Oct;12(10):904-22.
4 Dailymed: Terbutaline Sulfate Subcutaneous Injection
5 FDA Approval: Palbociclib for the Treatment of Postmenopausal Patients with Estrogen Receptor-Positive, HER2-Negative Metastatic Breast Cancer. Clin Cancer Res. 2015 Nov 1;21(21):4760-6. doi: 10.1158/1078-0432.CCR-15-1185. Epub 2015 Aug 31.
6 Clinical trials
7 Efflux transporters at the blood-brain barrier limit delivery and efficacy of cyclin-dependent kinase 4/6 inhibitor palbociclib (PD-0332991) in an orthotopic brain tumor model. J Pharmacol Exp Ther. 2015 Nov;355(2):264-71.
8 Progress with palbociclib in breast cancer: latest evidence and clinical considerations. Ther Adv Med Oncol. 2017 Feb;9(2):83-105.
9 Cytotoxicity of 34 FDA approved small-molecule kinase inhibitors in primary rat and human hepatocytes. Toxicol Lett. 2018 Jul;291:138-148. doi: 10.1016/j.toxlet.2018.04.010. Epub 2018 Apr 12.
10 Cdk4/6 inhibition induces epithelial-mesenchymal transition and enhances invasiveness in pancreatic cancer cells. Mol Cancer Ther. 2012 Oct;11(10):2138-48. doi: 10.1158/1535-7163.MCT-12-0562. Epub 2012 Aug 6.
11 Biological specificity of CDK4/6 inhibitors: dose response relationship, in vivo signaling, and composite response signature. Oncotarget. 2017 Jul 4;8(27):43678-43691. doi: 10.18632/oncotarget.18435.
12 Product Information. Talzenna (talazoparib). Pfizer U.S. Pharmaceuticals Group, New York, NY.
13 Product Information. Verzenio (abemaciclib). Lilly, Eli and Company, Indianapolis, IN.
14 Product Information. Ibrance (palbociclib). Pfizer U.S. Pharmaceuticals Group, New York, NY.
15 Cerner Multum, Inc. "Australian Product Information.".
16 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
17 Product Information. Daurismo (glasdegib). Pfizer U.S. Pharmaceuticals Group, New York, NY.
18 Product Information. Polivy (polatuzumab vedotin). Genentech, South San Francisco, CA.
19 Product Information. Tazverik (tazemetostat). Epizyme, Inc, Cambridge, MA.
20 Product Information. Pifeltro (doravirine). Merck & Company Inc, Whitehouse Station, NJ.
21 Product Information. Orladeyo (berotralstat). BioCryst Pharmaceuticals Inc, Durham, NC.
22 Product Information. Zepzelca (lurbinectedin). Jazz Pharmaceuticals, Palo Alto, CA.
23 Product Information. Tagrisso (osimertinib). Astra-Zeneca Pharmaceuticals, Wilmington, DE.
24 Product Information. Gavreto (pralsetinib). Blueprint Medicines Corporation, Cambridge, MA.
25 Product Information. Copiktra (duvelisib). Verastem, Inc., Needham, MA.
26 Product Information. Calquence (acalabrutinib). Astra-Zeneca Pharmaceuticals, Wilmington, DE.
27 Product Information. Koselugo (selumetinib). Astra-Zeneca Pharmaceuticals, Wilmington, DE.
28 Product Information. Ubrelvy (ubrogepant). Allergan Inc, Irvine, CA.
29 Product Information. Nurtec ODT (rimegepant). Biohaven Pharmaceuticals, New Haven, CT.
30 Product Information. Ocrevus (ocrelizumab). Genentech, South San Francisco, CA.
31 Product Information. Xeglyze (abametapir topical). Dr. Reddy's Laboratories Inc, Upper Saddle River, NJ.
32 Product Information. Xenleta (lefamulin). Nabriva Therapeutics US, Inc., King of Prussia, PA.
33 CDC. Centers for Disease Control and Prevention/ "Recommendations of the advisory committtee on immunization practices (ACIP): use of vaccines and immune globulins in persons with altered immunocompetence." MMWR Morb Mortal Wkly Rep 42(RR-04) (1993): 1-18. [PMID: 20300058]
34 Product Information. Odomzo (sonidegib). Novartis Pharmaceuticals, East Hanover, NJ.
35 EMA. European Medicines Agency. European Union "EMA - List of medicines under additional monitoring.".