Details of the Drug

General Information of Drug (ID: DM6QOVN)

Drug Name

HKI-272

Synonyms

Neratinib (ERBB2 inhibitor)

Indication

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Phase 3	[1], [2]

Therapeutic Class

Anticancer Agents

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 2

Molecular Weight (mw)

557

Topological Polar Surface Area (xlogp)

4.9

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

Clearance: The total clearance of drug is 216 L/h [3]
Elimination: 97.1% of the total dose is excreted in the feces and 1.13% in the urine [3]
Half-life: The concentration or amount of drug in body reduced by one-half in 7 - 17 hours [4]
Metabolism: The drug is metabolized via the CYP3A4 [4]
Vd: The volume of distribution (Vd) of drug is 6433 L [3]

Chemical Identifiers

Formula: C30H29ClN6O3
IUPAC Name: (E)-N-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]-3-cyano-7-ethoxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide
Canonical SMILES: CCOC1=C(C=C2C(=C1)N=CC(=C2NC3=CC(=C(C=C3)OCC4=CC=CC=N4)Cl)C#N)NC(=O)/C=C/CN(C)C
InChI: InChI=1S/C30H29ClN6O3/c1-4-39-28-16-25-23(15-26(28)36-29(38)9-7-13-37(2)3)30(20(17-32)18-34-25)35-21-10-11-27(24(31)14-21)40-19-22-8-5-6-12-33-22/h5-12,14-16,18H,4,13,19H2,1-3H3,(H,34,35)(H,36,38)/b9-7+
InChIKey: JWNPDZNEKVCWMY-VQHVLOKHSA-N

Cross-matching ID

PubChem CID: 9915743
ChEBI ID: CHEBI:61397
CAS Number: 698387-09-6
DrugBank ID: DB11828
TTD ID: D0Q9CY
INTEDE ID: DR1887
ACDINA ID: D00463

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Epidermal growth factor receptor (EGFR)	TTGKNB4	EGFR_HUMAN	Inhibitor	[5]
ERBB2 messenger RNA (HER2 mRNA)	TTR5TV4	ERBB2_HUMAN	Inhibitor	[6]
Erbb2 tyrosine kinase receptor (HER2)	TT6EO5L	ERBB2_HUMAN	Inhibitor	[7]
Vascular endothelial growth factor receptor 2 (KDR)	TTUTJGQ	VGFR2_HUMAN	Inhibitor	[5]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)_{Main DME}	DE4LYSA	CP3A4_HUMAN	Substrate	[8]

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Molecular Interaction Atlas (MIA)

MIA Detail

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
Vascular endothelial growth factor receptor 2 (KDR)	DTT	KDR	1.98E-01	0.11	0.2
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	1.04E-02	6.29E-02	3.54E-01

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from HKI-272 (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Arn-509	DMT81LZ	Major	Increased metabolism of HKI-272 caused by Arn-509 mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[48]
Gilteritinib	DMWQ4MZ	Moderate	Decreased clearance of HKI-272 due to the transporter inhibition by Gilteritinib.	Acute myeloid leukaemia [2A60]	[49]
Troleandomycin	DMUZNIG	Major	Decreased metabolism of HKI-272 caused by Troleandomycin mediated inhibition of CYP450 enzyme.	Bacterial infection [1A00-1C4Z]	[50]
MK-8228	DMOB58Q	Major	Decreased metabolism of HKI-272 caused by MK-8228 mediated inhibition of CYP450 enzyme.	Cytomegaloviral disease [1D82]	[50]
Ripretinib	DM958QB	Moderate	Decreased clearance of HKI-272 due to the transporter inhibition by Ripretinib.	Gastrointestinal stromal tumour [2B5B]	[48]
Berotralstat	DMWA2DZ	Major	Decreased clearance of HKI-272 due to the transporter inhibition by Berotralstat.	Innate/adaptive immunodeficiency [4A00]	[51]
PF-06463922	DMKM7EW	Major	Increased metabolism of HKI-272 caused by PF-06463922 mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[48]
IPI-145	DMWA24P	Major	Decreased metabolism of HKI-272 caused by IPI-145 mediated inhibition of CYP450 enzyme.	Mature B-cell leukaemia [2A82]	[50]
Arry-162	DM1P6FR	Moderate	Decreased clearance of HKI-272 due to the transporter inhibition by Arry-162.	Melanoma [2C30]	[48]
Ubrogepant	DM749I3	Moderate	Decreased clearance of HKI-272 due to the transporter inhibition by Ubrogepant.	Migraine [8A80]	[52]
Rimegepant	DMHOAUG	Moderate	Decreased clearance of HKI-272 due to the transporter inhibition by Rimegepant.	Migraine [8A80]	[53]
Fedratinib	DM4ZBK6	Major	Decreased metabolism of HKI-272 caused by Fedratinib mediated inhibition of CYP450 enzyme.	Myeloproliferative neoplasm [2A20]	[50]
Lefamulin	DME6G97	Moderate	Decreased metabolism of HKI-272 caused by Lefamulin mediated inhibition of CYP450 enzyme.	Pneumonia [CA40]	[54]
Relugolix	DMK7IWL	Major	Decreased clearance of HKI-272 due to the transporter inhibition by Relugolix.	Prostate cancer [2C82]	[55]
Voxelotor	DMCS6M5	Major	Decreased metabolism of HKI-272 caused by Voxelotor mediated inhibition of CYP450 enzyme.	Sickle-cell disorder [3A51]	[50]
Lusutrombopag	DMH6IKO	Moderate	Decreased clearance of HKI-272 due to the transporter inhibition by Lusutrombopag.	Thrombocytopenia [3B64]	[56]
Betrixaban	DM2C4RF	Moderate	Decreased clearance of HKI-272 due to the transporter inhibition by Betrixaban.	Venous thromboembolism [BD72]	[57]
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⏷ Show the Full List of 17 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
Mannitol	E00103	6251	Diluent; Flavoring agent; Lyophilization aid; Plasticizing agent; Tonicity agent
Crospovidone	E00626	Not Available	Disintegrant
Eisenoxyd	E00585	56841934	Colorant
Magnesium stearate	E00208	11177	lubricant
Polyethylene glycol 4000	E00654	Not Available	Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Polyvinyl alcohol	E00666	Not Available	Coating agent; Emulsion stabilizing agent; Film/Membrane-forming agent
Povidone	E00667	Not Available	Binding agent; Coating agent; Disintegrant; Film/membrane-forming agent; Solubilizing agent; Suspending agent
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
Haematite red	E00236	14833	Colorant
Hydrophobic colloidal silica	E00285	24261	Anticaking agent; Emulsion stabilizing agent; Glidant; Suspending agent; Viscosity-controlling agent
Cellulose microcrystalline	E00698	Not Available	Adsorbent; Suspending agent; Diluent
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⏷ Show the Full List of 14 Pharmaceutical Excipients of This Drug

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Neratinib 40 mg tablet	40 mg	Oral Tablet	Oral
Neratinib Maleate 40 mg tablet	40 mg	Tablet	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

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