Details of the Drug

General Information of Drug (ID: DMMX75K)

Drug Name
LEE011
Synonyms
Ribociclib; LEE011; 1211441-98-3; LEE-011; Kisqali; Ribociclib(LEE011); UNII-TK8ERE8P56; LEE 011; 7-cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; TK8ERE8P56; Ribociclib (LEE011); AK174906; 7-cyclopentyl-N,N-dimethyl-2-{[5-(piperazin-1-yl)pyridin-2-yl]amino}-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-cyclopentyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-7H-pyrrolo [2,3-d]pyrimidine-6-carboxylic acid dimethylamide; Ribociclib [USAN:INN]; LEE011A; Tube013
Indication
Disease Entry ICD 11 Status REF
Breast cancer 2C60-2C65 Phase 3 [1]
Solid tumour/cancer 2A00-2F9Z Phase 3 [2]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 434.5
Logarithm of the Partition Coefficient (xlogp) 2.2
Rotatable Bond Count (rotbonds) 5
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 7
ADMET Property
Half-life
The concentration or amount of drug in body reduced by one-half in 32.6 hours [3]
Chemical Identifiers
Formula
C23H30N8O
IUPAC Name
7-cyclopentyl-N,N-dimethyl-2-[(5-piperazin-1-ylpyridin-2-yl)amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide
Canonical SMILES
CN(C)C(=O)C1=CC2=CN=C(N=C2N1C3CCCC3)NC4=NC=C(C=C4)N5CCNCC5
InChI
InChI=1S/C23H30N8O/c1-29(2)22(32)19-13-16-14-26-23(28-21(16)31(19)17-5-3-4-6-17)27-20-8-7-18(15-25-20)30-11-9-24-10-12-30/h7-8,13-15,17,24H,3-6,9-12H2,1-2H3,(H,25,26,27,28)
InChIKey
RHXHGRAEPCAFML-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
44631912
CAS Number
1211441-98-3
DrugBank ID
DB11730
TTD ID
D08MXP
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 [4]
Cyclin-dependent kinase 6 (CDK6) TTO0FDJ CDK6_HUMAN Modulator [4]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Alanine aminotransferase 1 (GPT) OTOXOA0Q ALAT1_HUMAN Protein Interaction/Cellular Processes [5]
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
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 LEE011
DDI Drug Name DDI Drug ID Severity Mechanism Disease REF
Larotrectinib DM26CQR Moderate Decreased clearance of LEE011 due to the transporter inhibition by Larotrectinib. Solid tumour/cancer [2A00-2F9Z] [6]
Coadministration of a Drug Treating the Disease Different from LEE011 (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Remdesivir DMBFZ6L Moderate Increased risk of hepatotoxicity by the combination of LEE011 and Remdesivir. 1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019] [6]
Ivosidenib DM8S6T7 Major Increased risk of prolong QT interval by the combination of LEE011 and Ivosidenib. Acute myeloid leukaemia [2A60] [7]
Arn-509 DMT81LZ Major Increased metabolism of LEE011 caused by Arn-509 mediated induction of CYP450 enzyme. Acute myeloid leukaemia [2A60] [8]
Gilteritinib DMTI0ZO Major Increased risk of prolong QT interval by the combination of LEE011 and Gilteritinib. Acute myeloid leukaemia [2A60] [9]
Levalbuterol DM5YBO1 Major Increased risk of prolong QT interval by the combination of LEE011 and Levalbuterol. Asthma [CA23] [9]
Troleandomycin DMUZNIG Major Decreased metabolism of LEE011 caused by Troleandomycin mediated inhibition of CYP450 enzyme. Bacterial infection [1A00-1C4Z] [10]
Pexidartinib DMS2J0Z Major Increased risk of hepatotoxicity by the combination of LEE011 and Pexidartinib. Bone/articular cartilage neoplasm [2F7B] [11]
Talazoparib DM1KS78 Moderate Decreased clearance of LEE011 due to the transporter inhibition by Talazoparib. Breast cancer [2C60-2C6Y] [12]
HKI-272 DM6QOVN Major Decreased metabolism of LEE011 caused by HKI-272 mediated inhibition of CYP450 enzyme. Breast cancer [2C60-2C6Y] [13]
LY2835219 DM93VBZ Moderate Decreased metabolism of LEE011 caused by LY2835219 mediated inhibition of CYP450 enzyme. Breast cancer [2C60-2C6Y] [14]
PF-04449913 DMSB068 Major Increased risk of prolong QT interval by the combination of LEE011 and PF-04449913. Chronic myelomonocytic leukaemia [2A40] [9]
Osilodrostat DMIJC9X Major Increased risk of prolong QT interval by the combination of LEE011 and Osilodrostat. Cushing syndrome [5A70] [9]
MK-8228 DMOB58Q Moderate Decreased metabolism of LEE011 caused by MK-8228 mediated inhibition of CYP450 enzyme. Cytomegaloviral disease [1D82] [6]
Polatuzumab vedotin DMF6Y0L Moderate Decreased metabolism of LEE011 caused by Polatuzumab vedotin mediated inhibition of CYP450 enzyme. Diffuse large B-cell lymphoma [2A81] [15]
Deutetrabenazine DMUPFLI Major Increased risk of prolong QT interval by the combination of LEE011 and Deutetrabenazine. Dystonic disorder [8A02] [9]
Ingrezza DMVPLNC Major Increased risk of prolong QT interval by the combination of LEE011 and Ingrezza. Dystonic disorder [8A02] [9]
Eslicarbazepine DMZREFQ Moderate Increased metabolism of LEE011 caused by Eslicarbazepine mediated induction of CYP450 enzyme. Epilepsy/seizure [8A61-8A6Z] [6]
Bay 80-6946 DMLOS5R Moderate Decreased metabolism of LEE011 caused by Bay 80-6946 mediated inhibition of CYP450 enzyme. Follicular lymphoma [2A80] [16]
Tazemetostat DMWP1BH Major Decreased metabolism of LEE011 caused by Tazemetostat mediated inhibition of CYP450 enzyme. Follicular lymphoma [2A80] [17]
Ripretinib DM958QB Moderate Decreased metabolism of LEE011 caused by Ripretinib mediated inhibition of CYP450 enzyme. Gastrointestinal stromal tumour [2B5B] [6]
Avapritinib DMK2GZX Major Decreased metabolism of LEE011 caused by Avapritinib mediated inhibition of CYP450 enzyme. Gastrointestinal stromal tumour [2B5B] [10]
MK-1439 DM215WE Minor Decreased metabolism of LEE011 caused by MK-1439 mediated inhibition of CYP450 enzyme. Human immunodeficiency virus disease [1C60-1C62] [18]
Fostemsavir DM50ILT Major Increased risk of prolong QT interval by the combination of LEE011 and Fostemsavir. Human immunodeficiency virus disease [1C60-1C62] [9]
Berotralstat DMWA2DZ Moderate Decreased metabolism of LEE011 caused by Berotralstat mediated inhibition of CYP450 enzyme. Innate/adaptive immunodeficiency [4A00] [19]
Pemigatinib DM819JF Major Decreased metabolism of LEE011 caused by Pemigatinib mediated inhibition of CYP450 enzyme. Liver cancer [2C12] [10]
Brigatinib DM7W94S Major Decreased metabolism of LEE011 caused by Brigatinib mediated inhibition of CYP450 enzyme. Lung cancer [2C25] [6]
Lurbinectedin DMEFRTZ Major Decreased metabolism of LEE011 caused by Lurbinectedin mediated inhibition of CYP450 enzyme. Lung cancer [2C25] [20]
PF-06463922 DMKM7EW Moderate Increased metabolism of LEE011 caused by PF-06463922 mediated induction of CYP450 enzyme. Lung cancer [2C25] [6]
Pralsetinib DMWU0I2 Moderate Decreased metabolism of LEE011 caused by Pralsetinib mediated inhibition of CYP450 enzyme. Lung cancer [2C25] [21]
Capmatinib DMYCXKL Moderate Decreased metabolism of LEE011 caused by Capmatinib mediated inhibition of CYP450 enzyme. Lung cancer [2C25] [22]
Selpercatinib DMZR15V Major Decreased metabolism of LEE011 caused by Selpercatinib mediated inhibition of CYP450 enzyme. Lung cancer [2C25] [10]
IPI-145 DMWA24P Moderate Decreased metabolism of LEE011 caused by IPI-145 mediated inhibition of CYP450 enzyme. Mature B-cell leukaemia [2A82] [23]
Arry-162 DM1P6FR Moderate Decreased clearance of LEE011 due to the transporter inhibition by Arry-162. Melanoma [2C30] [6]
Ubrogepant DM749I3 Moderate Decreased metabolism of LEE011 caused by Ubrogepant mediated inhibition of CYP450 enzyme. Migraine [8A80] [24]
Rimegepant DMHOAUG Moderate Decreased metabolism of LEE011 caused by Rimegepant mediated inhibition of CYP450 enzyme. Migraine [8A80] [25]
Siponimod DM2R86O Major Increased risk of ventricular arrhythmias by the combination of LEE011 and Siponimod. Multiple sclerosis [8A40] [6]
Ocrelizumab DMEZ2KH Moderate Additive immunosuppressive effects by the combination of LEE011 and Ocrelizumab. Multiple sclerosis [8A40] [26]
Ozanimod DMT6AM2 Major Additive immunosuppressive effects by the combination of LEE011 and Ozanimod. Multiple sclerosis [8A40] [10]
Fedratinib DM4ZBK6 Minor Decreased metabolism of LEE011 caused by Fedratinib mediated inhibition of CYP450 enzyme. Myeloproliferative neoplasm [2A20] [6]
Entrectinib DMMPTLH Major Decreased metabolism of LEE011 caused by Entrectinib mediated inhibition of CYP450 enzyme. Non-small cell lung cancer [2C25] [6]
Rucaparib DM9PVX8 Major Increased risk of prolong QT interval by the combination of LEE011 and Rucaparib. Ovarian cancer [2C73] [9]
Abametapir DM2RX0I Moderate Decreased metabolism of LEE011 caused by Abametapir mediated inhibition of CYP450 enzyme. Pediculosis [1G00] [27]
Macimorelin DMQYJIR Major Increased risk of prolong QT interval by the combination of LEE011 and Macimorelin. Pituitary gland disorder [5A60-5A61] [28]
Lefamulin DME6G97 Major Increased risk of prolong QT interval by the combination of LEE011 and Lefamulin. Pneumonia [CA40] [29]
Relugolix DMK7IWL Major Increased risk of prolong QT interval by the combination of LEE011 and Relugolix. Prostate cancer [2C82] [9]
Darolutamide DMV7YFT Minor Decreased metabolism of LEE011 caused by Darolutamide mediated inhibition of CYP450 enzyme. Prostate cancer [2C82] [30]
Voxelotor DMCS6M5 Moderate Decreased metabolism of LEE011 caused by Voxelotor mediated inhibition of CYP450 enzyme. Sickle-cell disorder [3A51] [31]
Telotristat ethyl DMDIYFZ Moderate Increased metabolism of LEE011 caused by Telotristat ethyl mediated induction of CYP450 enzyme. Small intestine developmental anomaly [DA90] [6]
Fostamatinib DM6AUHV Moderate Decreased metabolism of LEE011 caused by Fostamatinib mediated inhibition of CYP450 enzyme. Thrombocytopenia [3B64] [32]
Elagolix DMB2C0E Moderate Increased metabolism of LEE011 caused by Elagolix mediated induction of CYP450 enzyme. Uterine fibroid [2E86] [6]
Fluticasone DMGCSVF Moderate Decreased metabolism of LEE011 caused by Fluticasone mediated inhibition of CYP450 enzyme. Vasomotor/allergic rhinitis [CA08] [6]
⏷ Show the Full List of 51 DDI Information of This Drug

References

1 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
2 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7383).
3 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
4 Dual CDK4/CDK6 inhibition induces cell-cycle arrest and senescence in neuroblastoma. Clin Cancer Res. 2013 Nov 15;19(22):6173-82.
5 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.
6 Cerner Multum, Inc. "Australian Product Information.".
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8 Product Information. Kisqali (ribociclib). Novartis Pharmaceuticals, East Hanover, NJ.
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11 Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
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14 Product Information. Verzenio (abemaciclib). Lilly, Eli and Company, Indianapolis, IN.
15 Product Information. Polivy (polatuzumab vedotin). Genentech, South San Francisco, CA.
16 Product Information. Aliqopa (copanlisib). Bayer Pharmaceutical Inc, West Haven, CT.
17 Product Information. Tazverik (tazemetostat). Epizyme, Inc, Cambridge, MA.
18 Product Information. Pifeltro (doravirine). Merck & Company Inc, Whitehouse Station, NJ.
19 Product Information. Orladeyo (berotralstat). BioCryst Pharmaceuticals Inc, Durham, NC.
20 Product Information. Zepzelca (lurbinectedin). Jazz Pharmaceuticals, Palo Alto, CA.
21 Product Information. Gavreto (pralsetinib). Blueprint Medicines Corporation, Cambridge, MA.
22 Product Information. Tabrecta (capmatinib). Novartis Pharmaceuticals, East Hanover, NJ.
23 Product Information. Copiktra (duvelisib). Verastem, Inc., Needham, MA.
24 Product Information. Ubrelvy (ubrogepant). Allergan Inc, Irvine, CA.
25 Product Information. Nurtec ODT (rimegepant). Biohaven Pharmaceuticals, New Haven, CT.
26 Product Information. Ocrevus (ocrelizumab). Genentech, South San Francisco, CA.
27 Product Information. Xeglyze (abametapir topical). Dr. Reddy's Laboratories Inc, Upper Saddle River, NJ.
28 Product Information. Macrilen (macimorelin). Aeterna Zentaris, Charleston, SC.
29 Product Information. Xenleta (lefamulin). Nabriva Therapeutics US, Inc., King of Prussia, PA.
30 Product Information. Nubeqa (darolutamide). Bayer HealthCare Pharmaceuticals Inc., Whippany, NJ.
31 DSouza DL, Levasseur LM, Nezamis J, Robbins DK, Simms L, Koch KM "Effect of alosetron on the pharmacokinetics of alprazolam." J Clin Pharmacol 41 (2001): 452-4. [PMID: 11304902]
32 Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.