NERATINIB MALEATE MONOHYDRATE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C30H29ClN6O3.C4H4O4.H2O
Molecular Weight	691.13
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	2
Charge	0

SHOW SMILES / InChI

Structure of NERATINIB MALEATE MONOHYDRATE

Structure Search

SMILES

O.OC(=O)\C=C/C(O)=O.CCOC1=C(NC(=O)\C=C\CN(C)C)C=C2C(=C1)N=CC(C#N)=C2NC3=CC=C(OCC4=NC=CC=C4)C(Cl)=C3

InChI

InChIKey=RLHWZKSMMZVQPD-VCGXHCGKSA-N

InChI=1S/C30H29ClN6O3.C4H4O4.H2O/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;5-3(6)1-2-4(7)8;/h5-12,14-16,18H,4,13,19H2,1-3H3,(H,34,35)(H,36,38);1-2H,(H,5,6)(H,7,8);1H2/b9-7+;2-1-;

HIDE SMILES / InChI

Molecular Formula	H2O
Molecular Weight	18.0153
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C30H29ClN6O3
Molecular Weight	557.043
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	1
Optical Activity	NONE

Molecular Formula	C4H4O4
Molecular Weight	116.0722
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	1
Optical Activity	NONE

Description
Sources: http://adisinsight.springer.com/drugs/800021154
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/26089701 | https://www.ncbi.nlm.nih.gov/pubmed/15715478

Neratinib (HKI-272) is a pan-HER inhibitor, this irreversible tyrosine kinase inhibitor binds and inhibits the tyrosine kinase activity of epidermal growth factor receptors, EGFR (or HER1), HER2 and HER4, which leads to reduced phosphorylation and activation of downstream signaling pathways. Neratinib is a modified form of the discontinued compound pelitinib, and was originally being develoAdditionally, phase II development of oral neratinib as a neoadjuvant therapy for breast cancer, as a second-line therapy for non-small cell lung cancer, and for other solid tumours is also in progress in numerous countries worldwide. ped by Wyeth (later Pfizer). Oral neratinib is awaiting approval as an extended adjuvant therapy for breast cancer in the EU and in the US. Blocking HER2 function by a small molecule kinase inhibitor, such as neratinib, represents an attractive alternate strategy for the growth inhibition of HER2-positive tumours.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Receptor protein-tyrosine kinase erbB-2 35 Target ID: CHEMBL1824 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15715478	Inhibitor 8297		59.0 nM [IC50]
Epidermal growth factor receptor erbB1 58 Target ID: CHEMBL203 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15715478	Inhibitor 8297		92.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
HER2-overexpressed/amplified breast cancer 3 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208051s000lbl.pdf	Primary	Approved 8429	NERLYNX Approved Use NERLYNX is indicated for the extended adjuvant treatment of adult patients with early stage HER2-overexpressed/amplified breast cancer, to follow adjuvant trastuzumab based therapy. Launch Date 2017
Breast cancer 434 Sources: http://adisinsight.springer.com/drugs/800021154	Primary	Phase III 656	Unknown Approved Use Unknown
Non-small cell lung cancer 206 Sources: http://adisinsight.springer.com/drugs/800021154	Primary	Phase II 1132	Unknown Approved Use Unknown
Colorectal cancer 101 Sources: http://adisinsight.springer.com/drugs/800021154	Primary	Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
73.1 ng/mL REVIEW https://www.ncbi.nlm.nih.gov/pubmed/27284682	240 mg 1 times / day steady-state, oral dose: 240 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	NERATINIB blood	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED
81.5 ng/mL REVIEW https://www.ncbi.nlm.nih.gov/pubmed/27284682	240 mg 1 times / day steady-state, oral dose: 240 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	NERATINIB blood	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED
76.3 ng/mL REVIEW https://www.ncbi.nlm.nih.gov/pubmed/27284682	240 mg single, oral dose: 240 mg route of administration: Oral experiment type: SINGLE co-administered:	NERATINIB blood	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED
71.8 ng/mL REVIEW https://www.ncbi.nlm.nih.gov/pubmed/27284682	240 mg single, oral dose: 240 mg route of administration: Oral experiment type: SINGLE co-administered:	NERATINIB blood	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED

AUC

Value	Dose	Analyte	Population
1060 ng × h/mL REVIEW https://www.ncbi.nlm.nih.gov/pubmed/27284682	240 mg 1 times / day steady-state, oral dose: 240 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	NERATINIB blood	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED
1110 ng × h/mL REVIEW https://www.ncbi.nlm.nih.gov/pubmed/27284682	240 mg 1 times / day steady-state, oral dose: 240 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	NERATINIB blood	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED
1640 ng × h/mL REVIEW https://www.ncbi.nlm.nih.gov/pubmed/27284682	240 mg single, oral dose: 240 mg route of administration: Oral experiment type: SINGLE co-administered:	NERATINIB blood	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED
891 ng × h/mL REVIEW https://www.ncbi.nlm.nih.gov/pubmed/27284682	240 mg single, oral dose: 240 mg route of administration: Oral experiment type: SINGLE co-administered:	NERATINIB blood	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED

T_1/2

Value	Dose	Analyte	Population
14.6 h REVIEW https://www.ncbi.nlm.nih.gov/pubmed/27284682	240 mg 1 times / day steady-state, oral dose: 240 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	NERATINIB blood	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED
22.7 h REVIEW https://www.ncbi.nlm.nih.gov/pubmed/27284682	240 mg 1 times / day steady-state, oral dose: 240 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	NERATINIB blood	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED
14.3 h REVIEW https://www.ncbi.nlm.nih.gov/pubmed/27284682	240 mg single, oral dose: 240 mg route of administration: Oral experiment type: SINGLE co-administered:	NERATINIB blood	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED
12.6 h REVIEW https://www.ncbi.nlm.nih.gov/pubmed/27284682	240 mg single, oral dose: 240 mg route of administration: Oral experiment type: SINGLE co-administered:	NERATINIB blood	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED

F_unbound

Value	Dose	Co-administered	Analyte	Population
1% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208051s000lbl.pdf			NERATINIB plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
400 mg 1 times / day steady, oral Highest studied dose Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19318484	unhealthy, 49.5 years (range: 42-63 years) n = 6 Health Status: unhealthy Condition: Non–small cell lung cancer \| breast cancer Age Group: 49.5 years (range: 42-63 years) Sex: M+F Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/19318484	DLT: Diarrhea... Disc. AE: Fatigue... Dose limiting toxicities: Diarrhea (grade 3, 3 patients) AEs leading to discontinuation/dose reduction: Fatigue (all grades, 5 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/19318484
240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208051s000lbl.pdf https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208051Orig1s000MultidisciplineR.pdf	unhealthy, 52 years n = 1408 Health Status: unhealthy Condition: HER2-positive early-stage breast cancer Age Group: 52 years Sex: F Population Size: 1408 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208051s000lbl.pdf https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208051Orig1s000MultidisciplineR.pdf	DLT: Diarrhea, Diarrhea... Dose limiting toxicities: Diarrhea (all grades, 95%) Diarrhea (grade 3, 40%) Diarrhea (grade 4, 0.1%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208051s000lbl.pdf https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208051Orig1s000MultidisciplineR.pdf
240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208051s000lbl.pdf	unhealthy, 52 years n = 1408 Health Status: unhealthy Condition: HER2-positive early-stage breast cancer Age Group: 52 years Sex: F Population Size: 1408 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208051s000lbl.pdf	Disc. AE: Nausea, Abdominal pain... Other AEs: Nausea, Abdominal pain... AEs leading to discontinuation/dose reduction: Nausea (grade 3, 2%) Abdominal pain (grade 3, 2%) Abdominal pain upper (grade 3, 2%) Abdominal pain lower (grade 3, 2%) Vomiting (grade 3, 3%) Fatigue (grade 3, 2%) Alanine aminotransferase increased (grade 3, 1%) Alanine aminotransferase increased (grade 4, 0.2%) Other AEs: Nausea (all grades, 43%) Abdominal pain (all grades, 36%) Abdominal pain upper (all grades, 36%) Abdominal pain lower (all grades, 36%) Vomiting (all grades, 26%) Stomatitis (all grades, 14%) Aphthous stomatitis (all grades, 14%) Mouth ulceration (all grades, 14%) Oral mucosal blistering (all grades, 14%) Mucosal inflammation (all grades, 14%) Oropharyngeal pain (all grades, 14%) Oral pain (all grades, 14%) Glossodynia (all grades, 14%) Glossitis (all grades, 14%) Cheilitis (all grades, 14%) Stomatitis (grade 3, 0.3%) Aphthous stomatitis (grade 3, 0.3%) Mouth ulceration (grade 3, 0.3%) Oral mucosal blistering (grade 3, 0.3%) Mucosal inflammation (grade 3, 0.3%) Oropharyngeal pain (grade 3, 0.3%) Oral pain (grade 3, 0.3%) Glossodynia (grade 3, 0.3%) Glossitis (grade 3, 0.3%) Cheilitis (grade 3, 0.3%) Dyspepsia (all grades, 10%) Dyspepsia (grade 3, 0.4%) Abdominal distension (all grades, 5%) Abdominal distension (grade 3, 0.3%) Dry mouth (all grades, 3%) Dry mouth (grade 3, 0.1%) Fatigue (all grades, 27%) Alanine aminotransferase increased (all grades, 9%) Aspartate aminotransferase increased (all grades, 7%) Aspartate aminotransferase increased (grade 3, 0.5%) Aspartate aminotransferase increased (grade 4, 0.2%) Urinary tract infection (all grades, 5%) Urinary tract infection (grade 3, 0.1%) Weight decreased (all grades, 5%) Weight decreased (grade 3, 0.1%) Decreased appetite (all grades, 12%) Decreased appetite (grade 3, 0.2%) Dehydration (all grades, 4%) Dehydration (grade 3, 0.9%) Dehydration (grade 4, 0.1%) Muscle spasms (all grades, 11%) Muscle spasms (grade 3, 0.1%) Epistaxis (all grades, 5%) Rash (all grades, 18%) Rash erythematous (all grades, 18%) Rash follicular (all grades, 18%) Generalized rash (all grades, 18%) Rash pruritic (all grades, 18%) Rash pustular (all grades, 18%) Maculopapular rash (all grades, 18%) Rash papular (all grades, 18%) Dermatitis (all grades, 18%) Dermatitis acneiform (all grades, 18%) Toxic skin eruption (all grades, 18%) Rash (grade 3, 0.6%) Rash erythematous (grade 3, 0.6%) Rash follicular (grade 3, 0.6%) Generalized rash (grade 3, 0.6%) Rash pruritic (grade 3, 0.6%) Rash pustular (grade 3, 0.6%) Maculopapular rash (grade 3, 0.6%) Rash papular (grade 3, 0.6%) Dermatitis (grade 3, 0.6%) Dermatitis acneiform (grade 3, 0.6%) Toxic skin eruption (grade 3, 0.6%) Dry skin (all grades, 6%) Nail disorder (all grades, 8%) Paronychia (all grades, 8%) Onychoclasis (all grades, 8%) Nail discoloration (all grades, 8%) Nail toxicity (all grades, 8%) Nail growth abnormal (all grades, 8%) Nail dystrophy (all grades, 8%) Nail disorder (grade 3, 0.3%) Paronychia (grade 3, 0.3%) Onychoclasis (grade 3, 0.3%) Nail discoloration (grade 3, 0.3%) Nail toxicity (grade 3, 0.3%) Nail growth abnormal (grade 3, 0.3%) Nail dystrophy (grade 3, 0.3%) Skin fissures (all grades, 2%) Skin fissures (grade 3, 0.1%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208051s000lbl.pdf
240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208051Orig1s000MultidisciplineR.pdf Page: p. 117	unhealthy, 52 years n = 1408 Health Status: unhealthy Condition: HER2-positive early-stage breast cancer Age Group: 52 years Sex: F Population Size: 1408 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208051Orig1s000MultidisciplineR.pdf Page: p. 117	Other AEs: Bilirubin increased, Bilirubin increased... Other AEs: Bilirubin increased (all grades, 11.1%) Bilirubin increased (grade 3, 0.1%) Alkaline phosphatase (all grades, 22.7%) Creatinine increased (all grades, 12.5%) Creatinine increased (grade 4, 0.1%) Creatinine increased (grade 3, 0.1%) Hypercalcemia (all grades, 11.2%) Hypercalcemia (grade 4, 0.2%) Hypercalcemia (grade 3, 0.4%) Hypermagnesemia (all grades, 5.2%) Hypermagnesemia (grade 4, 0.1%) Hypermagnesemia (grade 3, 0.9%) Hypernatremia (all grades, 10.3%) Hypernatremia (grade 4, 0.1%) Hypernatremia (grade 3, 0.1%) Hypoalbuminemia (all grades, 8.4%) Hypoalbuminemia (grade 3, 0.1%) Hypocalcemia (all grades, 48.9%) Hypocalcemia (grade 4, 0.9%) Hypocalcemia (grade 3, 0.1%) Hypokalemia (all grades, 7.5%) Hypokalemia (grade 4, 0.1%) Hypokalemia (grade 3, 0.3%) Hypomagnesemia (all grades, 7.2%) Hypomagnesemia (grade 4, 0.2%) Hypomagnesemia (grade 3, 0.4%) Hyponatremia (all grades, 11.6%) Hyponatremia (grade 3, 0.9%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208051Orig1s000MultidisciplineR.pdf Page: p. 117
180 mg 1 times / day steady, oral Dose: 180 mg, 1 times / day Route: oral Route: steady Dose: 180 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19318484	unhealthy, 56.5 years (range: 46-90 years) n = 6 Health Status: unhealthy Condition: Breast cancer Age Group: 56.5 years (range: 46-90 years) Sex: F Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/19318484	DLT: Diarrhea... Disc. AE: Fatigue... Dose limiting toxicities: Diarrhea (grade 3, 1 patient) AEs leading to discontinuation/dose reduction: Fatigue (all grades, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/19318484
320 mg 1 times / day steady, oral MTD Dose: 320 mg, 1 times / day Route: oral Route: steady Dose: 320 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19318484	unhealthy, 57 years (range: 34-80 years) n = 39 Health Status: unhealthy Condition: cancers Age Group: 57 years (range: 34-80 years) Sex: M+F Population Size: 39 Sources: https://pubmed.ncbi.nlm.nih.gov/19318484	Disc. AE: Diarrhea, Fatigue... Other AEs: Abdominal pain, Nausea... AEs leading to discontinuation/dose reduction: Diarrhea (all grades, 92%) Fatigue (all grades, 49%) Other AEs: Abdominal pain (all grades, 21%) Nausea (all grades, 54%) Vomiting (all grades, 49%) Anorexia (all grades, 33%) Rash (all grades, 8%) Sources: https://pubmed.ncbi.nlm.nih.gov/19318484

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inhibitor 1587 inducer 781	inhibitor 1767 inducer 389	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461 CYP2C19 1478 CYP1A2 1524 CYP2B6 810 L-type Ca channels 9	FMO 35 CYP3A 191	CYP1A2 701 CYP2B6 547

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208051Orig1s000MultidisciplineR.pdf#page=68 Page: -	no
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208051Orig1s000MultidisciplineR.pdf#page=68 Page: -	no
CYP2B6 1001	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208051Orig1s000MultidisciplineR.pdf#page=68 Page: -	no
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208051Orig1s000MultidisciplineR.pdf#page=68 Page: -	no
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208051Orig1s000MultidisciplineR.pdf#page=68 Page: -	no
CYP2C9 1819	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208051Orig1s000MultidisciplineR.pdf#page=68 Page: -	no
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208051Orig1s000MultidisciplineR.pdf#page=68 Page: -	no
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208051Orig1s000MultidisciplineR.pdf#page=68 Page: -	no
CYP3A4 1925	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208051Orig1s000MultidisciplineR.pdf#page=68 Page: -	no
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208051Orig1s000MultidisciplineR.pdf#page=68 Page: -	no
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208051Orig1s000MultidisciplineR.pdf#page=67 Page: -	yes [IC50 1 uM]	yes (co-administration study) Comment: NERATINIB increases digoxin Cmax& AUC Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208051Orig1s000MultidisciplineR.pdf#page=67 Page: -
L-type Ca channels 9	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208051Orig1s000MultidisciplineR.pdf#page=34 Page: -	yes [Inhibition 10 uM]

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208051Orig1s000MultidisciplineR.pdf#page=65 Page: -	major	yes (co-administration study) Comment: ketoconazole increased Cmax and AUC by 3.2- and 4.8-fold respectively, rifampin (a strong CYP3A4 inducer) decreased the Cmax and AUC of neratinib by 76% and 87%, respectively Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208051Orig1s000MultidisciplineR.pdf#page=65 Page: -
FMO 35	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208051Orig1s000MultidisciplineR.pdf#page=65 Page: -	minor
CYP3A 191	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208051Orig1s000MultidisciplineR.pdf#page=65 Page: -	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208051Orig1s000MultidisciplineR.pdf#page=37 Page: -

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:61397	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:61397
ChemicalBook	CB2855051	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB2855051
MolPort	MolPort-006-069-389	https://www.molport.com/shop/molecule-link/MolPort-006-069-389
Selleck Chemicals	Neratinib(HKI-272)	http://www.selleckchem.com/products/Neratinib(HKI-272).html
ZINC	ZINC000003916214	http://zinc15.docking.org/substances/ZINC000003916214
eMolecules	24195283	https://www.emolecules.com/cgi-bin/more?vid=24195283

PubMed

Title	Date	PubMed
		252160222
Antitumor activity of HKI-272, an orally active, irreversible inhibitor of the HER-2 tyrosine kinase.	2004 Jun 1	15173008
Irreversible EGFR inhibitor EKB-569 targets low-LET γ-radiation-triggered rel orchestration and potentiates cell death in squamous cell carcinoma.	2011	22242139
A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development.	2013 Nov	23956101

Patents

Sample Use Guides

In Vivo Use Guide

Patients who received 40, 80, or 120 mg experienced no dose-limiting toxicities. The study determined the maximum tolerated dose at 320 mg, with 240 mg being the therapeutic dose.

Route of Administration: Oral

In Vitro Use Guide

both very low (10 nM) and physiologically attainable concentrations of neratinib (133 nM) significantly inhibited the autophosphorylation of HER2/neu and activation of S6 in primary carcinosarcoma cells

Substance Class	Chemical Created by `admin` on `Sat Dec 16 19:11:27 GMT 2023` Edited by `admin` on `Sat Dec 16 19:11:27 GMT 2023`
Record UNII	KF5ZU8T8W2
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

NERATINIB MALEATE MONOHYDRATE

Common Name

English

2-BUTENAMIDE, N-(4-((3-CHLORO-4-(2-PYRIDINYLMETHOXY)PHENYL)AMINO)-3-CYANO-7-ETHOXY-6-QUINOLINYL)-4-(DIMETHYLAMINO)-, (2E)-, (2Z)-2-BUTENEDIOATE, HYDRATE (1:1:1)

Systematic Name

English

Code System Code Type Description

FDA UNII

KF5ZU8T8W2

Created by admin on Sat Dec 16 19:11:28 GMT 2023 , Edited by admin on Sat Dec 16 19:11:28 GMT 2023

PRIMARY

CAS

1144516-12-0

Created by admin on Sat Dec 16 19:11:28 GMT 2023 , Edited by admin on Sat Dec 16 19:11:28 GMT 2023

PRIMARY

PUBCHEM

25267298

Created by admin on Sat Dec 16 19:11:28 GMT 2023 , Edited by admin on Sat Dec 16 19:11:28 GMT 2023

PRIMARY

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					JJH94R3PWB

NERATINIB

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Amount:


					9RM7XY23ZS

NERATINIB MALEATE ANHYDROUS

ANHYDROUS->SOLVATE

Related Record Type Details


					G7S79C6K63

6-Amino-4-[[3-chloro-4-(2-pyridinylmethoxy)phenyl]amino]-7-ethoxy-3-quinolinecarbonitrile

IMPURITY -> PARENT

Amount:

Details

SMILES

InChI

DescriptionSources: http://adisinsight.springer.com/drugs/800021154Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/26089701 | https://www.ncbi.nlm.nih.gov/pubmed/15715478

Originator

Approval Year

Targets

Conditions

Approved Use

Launch Date

Approved Use

Approved Use

Approved Use

Cmax

AUC

T1/2

Funbound

Doses

AEs

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Tox targets

Sourcing

PubMed

Patents

Sample Use Guides

Description
Sources: http://adisinsight.springer.com/drugs/800021154
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/26089701 | https://www.ncbi.nlm.nih.gov/pubmed/15715478

C_max

T_1/2

F_unbound

Drug as perpetrator