Details of the Drug

General Information of Drug (ID: DM93VBZ)

• Drug Name: LY2835219
• Synonyms: Abemaciclib; 1231929-97-7; Verzenio; LY-2835219; UNII-60UAB198HK; LY2835219 (free base)

Indication

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Approved	[1]
Solid tumour/cancer	2A00-2F9Z	Phase 3	[2]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 1:
  Molecular Weight (mw); 506.6
  Logarithm of the Partition Coefficient (xlogp); 3.8
  Rotatable Bond Count (rotbonds); 7
  Hydrogen Bond Donor Count (hbonddonor); 1
  Hydrogen Bond Acceptor Count (hbondacc); 9
• ADMET Property:
  Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 300 mcg/L [3]
  Absorption Tmax: The time to maximum plasma concentration (Tmax) is 30-60 min [3]
  Bioavailability: The bioavailability of drug is 75% [3]
  Clearance: The clearance of drug is 26.0 L/h []
  Elimination: Following a single oral dose of 150mg radiolabeled abemaciclib, approximately 81% of the total dose was recovered in feces while 3% of the dose was detected in urine []
  Half-life: The concentration or amount of drug in body reduced by one-half in 18.3 hours []
  Metabolism: The drug is metabolized via the hepatic []
  Vd: The volume of distribution (Vd) of drug is 690.3 L []
• Chemical Identifiers:
  Formula: C27H32F2N8
  IUPAC Name: N-[5-[(4-ethylpiperazin-1-yl)methyl]pyridin-2-yl]-5-fluoro-4-(7-fluoro-2-methyl-3-propan-2-ylbenzimidazol-5-yl)pyrimidin-2-amine
  Canonical SMILES: CCN1CCN(CC1)CC2=CN=C(C=C2)NC3=NC=C(C(=N3)C4=CC5=C(C(=C4)F)N=C(N5C(C)C)C)F
  InChI: InChI=1S/C27H32F2N8/c1-5-35-8-10-36(11-9-35)16-19-6-7-24(30-14-19)33-27-31-15-22(29)25(34-27)20-12-21(28)26-23(13-20)37(17(2)3)18(4)32-26/h6-7,12-15,17H,5,8-11,16H2,1-4H3,(H,30,31,33,34)
  InChIKey: UZWDCWONPYILKI-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 46220502
  CAS Number: 1231929-97-7
  DrugBank ID: DB12001
  TTD ID: D05SBO
  VARIDT ID: DR00097
  INTEDE ID: DR0028
  ACDINA ID: D00003
• 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 Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Multidrug and toxin extrusion protein 2 (SLC47A2)	DT3TX4H	S47A2_HUMAN	Substrate	[5]
Multidrug and toxin extrusion protein 1 (SLC47A1)	DTZGT0P	S47A1_HUMAN	Substrate	[5]
Organic cation transporter 2 (SLC22A2)	DT9IDPW	S22A2_HUMAN	Substrate	[5]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[6]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Apolipoprotein E (APOE)	OTFOWL2H	APOE_HUMAN	Gene/Protein Processing	[7]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Gene/Protein Processing	[8]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Gene/Protein Processing	[8]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Gene/Protein Processing	[9]
BRCA1-associated RING domain protein 1 (BARD1)	OTTC0Z9Y	BARD1_HUMAN	Gene/Protein Processing	[7]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2)	OTW8V2V1	ABCG2_HUMAN	Gene/Protein Processing	[9]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Gene/Protein Processing	[8]
Cyclin-A2 (CCNA2)	OTPHHYZJ	CCNA2_HUMAN	Gene/Protein Processing	[10]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Gene/Protein Processing	[7]
Ephrin-B3 (EFNB3)	OT12WTXQ	EFNB3_HUMAN	Gene/Protein Processing	[7]

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
Multidrug and toxin extrusion protein 1 (SLC47A1)	DTP	MATE1	1.37E-11	-4.84E-01	-6.68E-01
Organic cation transporter 2 (SLC22A2)	DTP	SLC22A2	6.98E-01	-1.97E-02	-8.16E-02
Multidrug and toxin extrusion protein 2 (SLC47A2)	DTP	MATE2	1.49E-18	1.67E-01	6.92E-01
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	5.59E-39	-3.76E-01	-1.64E+00

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from LY2835219 (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Remdesivir	DMBFZ6L	Moderate	Increased risk of hepatotoxicity by the combination of LY2835219 and Remdesivir.	1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019]	[11]
Ivosidenib	DM8S6T7	Moderate	Increased metabolism of LY2835219 caused by Ivosidenib mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[12]
Troleandomycin	DMUZNIG	Major	Decreased metabolism of LY2835219 caused by Troleandomycin mediated inhibition of CYP450 enzyme.	Bacterial infection [1A00-1C4Z]	[12]
Erdafitinib	DMI782S	Moderate	Increased metabolism of LY2835219 caused by Erdafitinib mediated induction of CYP450 enzyme.	Bladder cancer [2C94]	[13]
Pexidartinib	DMS2J0Z	Major	Increased risk of hepatotoxicity by the combination of LY2835219 and Pexidartinib.	Bone/articular cartilage neoplasm [2F7B]	[14]
MK-8228	DMOB58Q	Moderate	Decreased metabolism of LY2835219 caused by MK-8228 mediated inhibition of CYP450 enzyme.	Cytomegaloviral disease [1D82]	[12]
Eslicarbazepine	DMZREFQ	Moderate	Increased metabolism of LY2835219 caused by Eslicarbazepine mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[12]
Brigatinib	DM7W94S	Moderate	Increased metabolism of LY2835219 caused by Brigatinib mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[12]
PF-06463922	DMKM7EW	Moderate	Increased metabolism of LY2835219 caused by PF-06463922 mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[12]
Siponimod	DM2R86O	Major	Additive immunosuppressive effects by the combination of LY2835219 and Siponimod.	Multiple sclerosis [8A40]	[11]
Ozanimod	DMT6AM2	Major	Additive immunosuppressive effects by the combination of LY2835219 and Ozanimod.	Multiple sclerosis [8A40]	[15]
Fedratinib	DM4ZBK6	Moderate	Decreased metabolism of LY2835219 caused by Fedratinib mediated inhibition of CYP450 enzyme.	Myeloproliferative neoplasm [2A20]	[12]
Voxelotor	DMCS6M5	Moderate	Decreased metabolism of LY2835219 caused by Voxelotor mediated inhibition of CYP450 enzyme.	Sickle-cell disorder [3A51]	[12]
Telotristat ethyl	DMDIYFZ	Moderate	Increased metabolism of LY2835219 caused by Telotristat ethyl mediated induction of CYP450 enzyme.	Small intestine developmental anomaly [DA90]	[12]
Larotrectinib	DM26CQR	Moderate	Decreased metabolism of LY2835219 caused by Larotrectinib mediated inhibition of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[12]

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

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Sodium stearyl fumarate	E00545	23665634	lubricant
Carmellose sodium	E00625	Not Available	Disintegrant
Eisenoxyd	E00585	56841934	Colorant
Ferric hydroxide oxide yellow	E00539	23320441	Colorant
Lactose monohydrate	E00393	104938	Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Silicon dioxide	E00670	Not Available	Anticaking agent; Opacifying agent; Viscosity-controlling agent
Talc	E00520	16211421	Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Water	E00035	962	Solvent

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Abemaciclib 200 mg tablet	200 mg	Oral Tablet	Oral
Abemaciclib 50 mg tablet	50 mg	Oral Tablet	Oral
Abemaciclib 150 mg tablet	150 mg	Oral Tablet	Oral
Abemaciclib 100 mg tablet	100 mg	Oral Tablet	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

• [1] 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
• [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: 7382).
• [3] Pharmacokinetic profile of nicorandil in humans: an overview. J Cardiovasc Pharmacol. 1992;20 Suppl 3:S34-44.
• [4] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [5] Abemaciclib Inhibits Renal Tubular Secretion Without Changing Glomerular Filtration Rate. Clin Pharmacol Ther. 2019 May;105(5):1187-1195.
• [6] LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]-Abemaciclib.
• [7] 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.
• [8] In vitro therapeutic effects of abemaciclib on triple-negative breast cancer cells. J Biochem Mol Toxicol. 2021 Sep;35(9):e22858. doi: 10.1002/jbt.22858. Epub 2021 Jul 26.
• [9] Effect of abemaciclib (LY2835219) on enhancement of chemotherapeutic agents in ABCB1 and ABCG2 overexpressing cells in vitro and in vivo. Biochem Pharmacol. 2017 Jan 15;124:29-42. doi: 10.1016/j.bcp.2016.10.015. Epub 2016 Nov 2.
• [10] CDK4/6 Inhibition Controls Proliferation of Bladder Cancer and Transcription of RB1. J Urol. 2016 Mar;195(3):771-9. doi: 10.1016/j.juro.2015.08.082. Epub 2015 Aug 28.
• [11] Cerner Multum, Inc. "Australian Product Information.".
• [12] Product Information. Verzenio (abemaciclib). Lilly, Eli and Company, Indianapolis, IN.
• [13] Product Information. Balversa (erdafitinib). Janssen Products, LP, Horsham, PA.
• [14] Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
• [15] Cerner Multum, Inc. "UK Summary of Product Characteristics.".