DGIdb - NERATINIB Drug Record

NERATINIB chembl:CHEMBL180022 ApprovedAntineoplastic

Alternate Names:

HKI-272
NERATINIB
CDP-820
WAY-179272
HKI 272
chembl:CHEMBL180022
chemidplus:698387-09-6
pubchem.compound:9915743
rxcui:1940643
drugbank:11828

Drug Info:

FDA Approval	not approved
Drug Class	Small molecule
Drug Indications	antineoplastic agent
Drug Class	Kinase Inhibitors

(10 More Sources)

Publications:

Yang et al., 2001, Development of ABX-EGF, a fully human anti-EGF receptor monoclonal antibody, for cancer therapy., Crit. Rev. Oncol. Hematol.
Rossi A et al., 2013, Should epidermal growth factor receptor tyrosine kinase inhibitors be considered ideal drugs for the treatment of selected advanced non-small cell lung cancer patients?, Cancer Treat Rev
Mayo C et al., 2012, Pharmacogenetics of EGFR in lung cancer: perspectives and clinical applications., Pharmacogenomics
Van Cutsem et al., 2009, Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer., N. Engl. J. Med.
Vermorken JB et al., 2008, Platinum-based chemotherapy plus cetuximab in head and neck cancer., N Engl J Med
Funke S et al., 2008, Pharmacogenetics in colorectal cancer: a systematic review., Pharmacogenomics
Giusti RM et al., 2008, U.S. Food and Drug Administration approval: panitumumab for epidermal growth factor receptor-expressing metastatic colorectal carcinoma with progression following fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens., Clin Cancer Res
Jonker et al., 2007, Cetuximab for the treatment of colorectal cancer., N. Engl. J. Med.
Bonner JA et al., 2006, Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck., N Engl J Med
Normanno N et al., 2006, Epidermal growth factor receptor (EGFR) signaling in cancer., Gene
Thatcher N et al., 2005, Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: results from a randomised, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer)., Lancet
Herbst RS et al., 2004, Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: a phase III trial--INTACT 2., J Clin Oncol
Giaccone G et al., 2004, Gefitinib in combination with gemcitabine and cisplatin in advanced non-small-cell lung cancer: a phase III trial--INTACT 1., J Clin Oncol
Jorissen RN et al., 2003, Epidermal growth factor receptor: mechanisms of activation and signalling., Exp Cell Res
Mallon et al., 2011, Antitumor efficacy of PKI-587, a highly potent dual PI3K/mTOR kinase inhibitor., Clin. Cancer Res.
Balak et al., 2006, Novel D761Y and common secondary T790M mutations in epidermal growth factor receptor-mutant lung adenocarcinomas with acquired resistance to kinase inhibitors., Clin. Cancer Res.
Udager et al., 2015, High-Frequency Targetable EGFR Mutations in Sinonasal Squamous Cell Carcinomas Arising from Inverted Sinonasal Papilloma., Cancer Res.
Kobayashi et al., 2015, EGFR Exon 18 Mutations in Lung Cancer: Molecular Predictors of Augmented Sensitivity to Afatinib or Neratinib as Compared with First- or Third-Generation TKIs., Clin. Cancer Res.
Sequist et al., 2010, Neratinib, an irreversible pan-ErbB receptor tyrosine kinase inhibitor: results of a phase II trial in patients with advanced non-small-cell lung cancer., J. Clin. Oncol.
Ercan et al., 2015, EGFR Mutations and Resistance to Irreversible Pyrimidine-Based EGFR Inhibitors., Clin. Cancer Res.
Greulich et al., 2012, Functional analysis of receptor tyrosine kinase mutations in lung cancer identifies oncogenic extracellular domain mutations of ERBB2., Proc. Natl. Acad. Sci. U.S.A.
Martin et al., 2013, A phase two randomised trial of neratinib monotherapy versus lapatinib plus capecitabine combination therapy in patients with HER2+ advanced breast cancer., Eur. J. Cancer
Chan et al., 2016, Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial., Lancet Oncol.
Awada et al., 2016, Neratinib Plus Paclitaxel vs Trastuzumab Plus Paclitaxel in Previously Untreated Metastatic ERBB2-Positive Breast Cancer: The NEfERT-T Randomized Clinical Trial., JAMA Oncol
Hanker et al., 2017, An Acquired HER2(T798I) Gatekeeper Mutation Induces Resistance to Neratinib in a Patient with HER2 Mutant-Driven Breast Cancer., Cancer Discov
Zuo et al., 2016, Dual Characteristics of Novel HER2 Kinase Domain Mutations in Response to HER2-Targeted Therapies in Human Breast Cancer., Clin. Cancer Res.
Kodack et al., 2017, The brain microenvironment mediates resistance in luminal breast cancer to PI3K inhibition through HER3 activation., Sci Transl Med
Lopez et al., 2015, Dual HER2/PIK3CA Targeting Overcomes Single-Agent Acquired Resistance in HER2-Amplified Uterine Serous Carcinoma Cell Lines In Vitro and In Vivo., Mol. Cancer Ther.
Kavuri et al., 2015, HER2 activating mutations are targets for colorectal cancer treatment., Cancer Discov
Bose et al., 2013, Activating HER2 mutations in HER2 gene amplification negative breast cancer., Cancer Discov
Kosaka et al., 2017, Response Heterogeneity of EGFR and HER2 Exon 20 Insertions to Covalent EGFR and HER2 Inhibitors., Cancer Res.
Ma et al., 2017, Neratinib Efficacy and Circulating Tumor DNA Detection of HER2 Mutations in HER2 Nonamplified Metastatic Breast Cancer., Clin. Cancer Res.
Gandhi et al., 2014, Phase I study of neratinib in combination with temsirolimus in patients with human epidermal growth factor receptor 2-dependent and other solid tumors., J. Clin. Oncol.
Kancha et al., 2011, Differential sensitivity of ERBB2 kinase domain mutations towards lapatinib., PLoS ONE
Ali et al., 2014, Response of an ERBB2-mutated inflammatory breast carcinoma to human epidermal growth factor receptor 2-targeted therapy., J. Clin. Oncol.
Lee et al., 2006, Somatic mutations of ERBB2 kinase domain in gastric, colorectal, and breast carcinomas., Clin. Cancer Res.
Chang et al., 2016, Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity., Nat. Biotechnol.
MacConaill et al., 2014, Prospective enterprise-level molecular genotyping of a cohort of cancer patients., J Mol Diagn
Burstein et al., 2010, Neratinib, an irreversible ErbB receptor tyrosine kinase inhibitor, in patients with advanced ErbB2-positive breast cancer., J. Clin. Oncol.
Chow et al., 2013, Combination neratinib (HKI-272) and paclitaxel therapy in patients with HER2-positive metastatic breast cancer., Br. J. Cancer
Lin et al., 2012, A phase II study of afatinib (BIBW 2992), an irreversible ErbB family blocker, in patients with HER2-positive metastatic breast cancer progressing after trastuzumab., Breast Cancer Res. Treat.
Canonici A et al., 2013, Neratinib overcomes trastuzumab resistance in HER2 amplified breast cancer., Oncotarget
Saura et al., 2014, Safety and efficacy of neratinib in combination with capecitabine in patients with metastatic human epidermal growth factor receptor 2-positive breast cancer., J. Clin. Oncol.
Martin M et al., 2017, Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebo-controlled, phase 3 trial., Lancet Oncol
Singh H et al., 2018, U.S. Food and Drug Administration Approval: Neratinib for the Extended Adjuvant Treatment of Early-Stage HER2-Positive Breast Cancer., Clin Cancer Res
Dogruluk et al., 2015, Identification of Variant-Specific Functions of PIK3CA by Rapid Phenotyping of Rare Mutations., Cancer Res.
Hayes et al., 2016, Long-Term ERK Inhibition in KRAS-Mutant Pancreatic Cancer Is Associated with MYC Degradation and Senescence-like Growth Suppression., Cancer Cell

NERATINIB HERC2

Interaction Score: 11.24

Interaction Types & Directionality:

n/a

Interaction Info:

Clinical Status preclinical

Pathway activation

Variant Effect gain-of-function

PMIDs:
23220880

Sources:
DoCM
NERATINIB ERBB2

Interaction Score: 1.41

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Evidence Type Actionable

combination therapy Capecitabine + Neratinib

Approval Status FDA approved

PMIDs:
22908275 23953056 26874901 27078022 28274957 27697991 28539475 26333383 26243863 23220880 28363995 28679771 24323026 22046346 24516025 16397024 26619011 25157968 20142587 23632474 22418700 24009064 25287822 29146401 29523624

Sources:
TALC MyCancerGenome TdgClinicalTrial JAX-CKB ChemblInteractions DoCM CIViC MyCancerGenomeClinicalTrial PharmGKB TTD FDA OncoKB
NERATINIB EGFR

Interaction Score: 0.87

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Indication/Tumor Type head and neck squamous cell carcinoma

Approval Status Phase II

Indication/Tumor Type non-small cell lung carcinoma

PMIDs:
11255078 23022519 22594511 19339720 18784101 18681783 18316547 18003960 16467544 16377102 16257339 14990633 14990632 12648464 21325073 17085664 25931286 26206867 20479403 25948633

Sources:
TALC TdgClinicalTrial JAX-CKB ChemblInteractions PharmGKB TTD
NERATINIB PGR

Interaction Score: 0.22

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
PharmGKB FDA
NERATINIB PIK3CA

Interaction Score: 0.16

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type breast cancer

Response Type sensitive

Approval Status Preclinical

PMIDs:
26243863 26333383 26627007

Sources:
JAX-CKB
NERATINIB KRAS

Interaction Score: 0.13

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Neratinib + Trastuzumab

Indication/Tumor Type colorectal cancer

Response Type resistant

PMIDs:
26725216 26243863

Sources:
JAX-CKB
NERATINIB BRAF

Interaction Score: 0.12

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type colorectal cancer

Response Type sensitive

Approval Status Preclinical

PMIDs:
26243863

Sources:
JAX-CKB
NERATINIB ESR2

Interaction Score: 0.09

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
PharmGKB
NERATINIB ESR1

Interaction Score: 0.06

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
PharmGKB FDA
NERATINIB KDR

Interaction Score: 0.04

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
TTD
NERATINIB YES1

Interaction Score: 0.03

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC

MyCancerGenome: NERATINIB
- Version: 20-Jun-2017
Alternate Names:

HKI-272 Development Name

NERATINIB Generic Name

Drug Info:

Drug Class Kinase Inhibitors

Publications:
TdgClinicalTrial: NERATINIB
- Version: January-2014
Alternate Names:

Drug Info:

Drug Indications antineoplastic agent

Drug Class Small molecule

FDA Approval not approved

Publications:

JAX-CKB: Neratinib

Version: 27-September-2017

Alternate Names:

Drug Info:

Publications:

Dogruluk et al., 2015, Identification of Variant-Specific Functions of PIK3CA by Rapid Phenotyping of Rare Mutations., Cancer Res.

Lopez et al., 2015, Dual HER2/PIK3CA Targeting Overcomes Single-Agent Acquired Resistance in HER2-Amplified Uterine Serous Carcinoma Cell Lines In Vitro and In Vivo., Mol. Cancer Ther.

Kavuri et al., 2015, HER2 activating mutations are targets for colorectal cancer treatment., Cancer Discov

DoCM: NERATINIB

Version: 27-September-2017

Alternate Names:

Drug Info:

Publications:

Bose et al., 2013, Activating HER2 mutations in HER2 gene amplification negative breast cancer., Cancer Discov

Chang et al., 2016, Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity., Nat. Biotechnol.

Ali et al., 2014, Response of an ERBB2-mutated inflammatory breast carcinoma to human epidermal growth factor receptor 2-targeted therapy., J. Clin. Oncol.

PharmGKB: neratinib

Version: 18-August-2020

Alternate Names:

Drug Info:

Publications:

Bose et al., 2013, Activating HER2 mutations in HER2 gene amplification negative breast cancer., Cancer Discov

Funke S et al., 2008, Pharmacogenetics in colorectal cancer: a systematic review., Pharmacogenomics

Herbst RS et al., 2004, Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: a phase III trial--INTACT 2., J Clin Oncol

CIViC: NERATINIB

Version: 14-September-2020

Alternate Names:

Drug Info:

Publications:

Ma et al., 2017, Neratinib Efficacy and Circulating Tumor DNA Detection of HER2 Mutations in HER2 Nonamplified Metastatic Breast Cancer., Clin. Cancer Res.

Canonici A et al., 2013, Neratinib overcomes trastuzumab resistance in HER2 amplified breast cancer., Oncotarget

Singh H et al., 2018, U.S. Food and Drug Administration Approval: Neratinib for the Extended Adjuvant Treatment of Early-Stage HER2-Positive Breast Cancer., Clin Cancer Res

DTC: NERATINIB
- Version: 02-September-2020
Alternate Names:

CHEMBL180022 ChEMBL Drug ID

Drug Info:

Publications:
TALC: NERATINIB
- Version: 12-May-2016
Alternate Names:

NERATINIB Primary Drug Name

NERATINIB Drug Generic Name

HKI-272 Drug Synonym

Drug Info:

Publications:
TTD: HKI-272
- Version: 2020.06.01
Alternate Names:

D0Q9CY TTD Drug ID

Drug Info:

Publications:
ChemblInteractions: CHEMBL180022
- Version: chembl_23
Alternate Names:

Drug Info:

Publications:
ChemblDrugs: chembl:CHEMBL180022
- Version: ChEMBL_27
Alternate Names:

Drug Info:

Publications:
MyCancerGenomeClinicalTrial: NERATINIB
- Version: 30-February-2014
Alternate Names:

Drug Info:

Publications:
OncoKB: Neratinib
- Version: 23-July-2020
Alternate Names:

Drug Info:

Publications:
FDA: Neratinib
- Version: 04-September-2020
Alternate Names:

Drug Info:

Publications:

Clinical Status	preclinical
Pathway	activation
Variant Effect	gain-of-function

Evidence Type	Actionable
combination therapy	Capecitabine + Neratinib
Approval Status	FDA approved

Indication/Tumor Type	head and neck squamous cell carcinoma
Approval Status	Phase II
Indication/Tumor Type	non-small cell lung carcinoma

Indication/Tumor Type	breast cancer
Response Type	sensitive
Approval Status	Preclinical

combination therapy	Neratinib + Trastuzumab
Indication/Tumor Type	colorectal cancer
Response Type	resistant

NERATINIB	Primary Drug Name
NERATINIB	Drug Generic Name
HKI-272	Drug Synonym

NERATINIB Drug Record

NERATINIB chembl:CHEMBL180022 ApprovedAntineoplastic

Alternate Names:

Drug Info:

Publications:

Interaction Types & Directionality: n/a

Interaction Info: Clinical Status preclinical Pathway activation Variant Effect gain-of-function

PMIDs: 23220880

Sources: DoCM

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Evidence Type Actionable combination therapy Capecitabine + Neratinib Approval Status FDA approved

PMIDs: 22908275 23953056 26874901 27078022 28274957 27697991 28539475 26333383 26243863 23220880 28363995 28679771 24323026 22046346 24516025 16397024 26619011 25157968 20142587 23632474 22418700 24009064 25287822 29146401 29523624

Sources: TALC MyCancerGenome TdgClinicalTrial JAX-CKB ChemblInteractions DoCM CIViC MyCancerGenomeClinicalTrial PharmGKB TTD FDA OncoKB

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Indication/Tumor Type head and neck squamous cell carcinoma Approval Status Phase II Indication/Tumor Type non-small cell lung carcinoma

PMIDs: 11255078 23022519 22594511 19339720 18784101 18681783 18316547 18003960 16467544 16377102 16257339 14990633 14990632 12648464 21325073 17085664 25931286 26206867 20479403 25948633

Sources: TALC TdgClinicalTrial JAX-CKB ChemblInteractions PharmGKB TTD

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: None found

Sources: PharmGKB FDA

Interaction Types & Directionality: n/a

Interaction Info: Indication/Tumor Type breast cancer Response Type sensitive Approval Status Preclinical

PMIDs: 26243863 26333383 26627007

Sources: JAX-CKB

Interaction Types & Directionality: n/a

Interaction Info: combination therapy Neratinib + Trastuzumab Indication/Tumor Type colorectal cancer Response Type resistant

PMIDs: 26725216 26243863

Sources: JAX-CKB

Interaction Types & Directionality: n/a

Interaction Info: Indication/Tumor Type colorectal cancer Response Type sensitive Approval Status Preclinical

PMIDs: 26243863

Sources: JAX-CKB

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: None found

Sources: PharmGKB

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: None found

Sources: PharmGKB FDA

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: None found

Sources: TTD

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: None found

Sources: DTC

MyCancerGenome: NERATINIB

Alternate Names: HKI-272 Development Name NERATINIB Generic Name

Drug Info: Drug Class Kinase Inhibitors

Publications:

TdgClinicalTrial: NERATINIB

Alternate Names:

Drug Info: Drug Indications antineoplastic agent Drug Class Small molecule FDA Approval not approved

Publications:

JAX-CKB: Neratinib

Alternate Names:

Drug Info:

DoCM: NERATINIB

Alternate Names:

Drug Info:

PharmGKB: neratinib

Alternate Names:

Drug Info:

CIViC: NERATINIB

Alternate Names:

Drug Info:

DTC: NERATINIB

Alternate Names: CHEMBL180022 ChEMBL Drug ID

Drug Info:

Publications:

TALC: NERATINIB

Alternate Names: NERATINIB Primary Drug Name NERATINIB Drug Generic Name HKI-272 Drug Synonym

Drug Info:

Publications:

TTD: HKI-272

Alternate Names: D0Q9CY TTD Drug ID

Drug Info:

Interaction Types & Directionality:

n/a

Interaction Info:

Clinical Status preclinical

Pathway activation

Variant Effect gain-of-function

PMIDs:
23220880

Sources:
DoCM

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Evidence Type Actionable

combination therapy Capecitabine + Neratinib

Approval Status FDA approved

PMIDs:
22908275 23953056 26874901 27078022 28274957 27697991 28539475 26333383 26243863 23220880 28363995 28679771 24323026 22046346 24516025 16397024 26619011 25157968 20142587 23632474 22418700 24009064 25287822 29146401 29523624

Sources:
TALC MyCancerGenome TdgClinicalTrial JAX-CKB ChemblInteractions DoCM CIViC MyCancerGenomeClinicalTrial PharmGKB TTD FDA OncoKB

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Indication/Tumor Type head and neck squamous cell carcinoma

Approval Status Phase II

Indication/Tumor Type non-small cell lung carcinoma

PMIDs:
11255078 23022519 22594511 19339720 18784101 18681783 18316547 18003960 16467544 16377102 16257339 14990633 14990632 12648464 21325073 17085664 25931286 26206867 20479403 25948633

Sources:
TALC TdgClinicalTrial JAX-CKB ChemblInteractions PharmGKB TTD

Interaction Types & Directionality:

n/a

PMIDs:
None found

Sources:
PharmGKB FDA

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type breast cancer

Response Type sensitive

Approval Status Preclinical

PMIDs:
26243863 26333383 26627007

Sources:
JAX-CKB

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Neratinib + Trastuzumab

Indication/Tumor Type colorectal cancer

Response Type resistant

PMIDs:
26725216 26243863

Sources:
JAX-CKB

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type colorectal cancer

Response Type sensitive

Approval Status Preclinical

PMIDs:
26243863

Sources:
JAX-CKB

Interaction Types & Directionality:

n/a

PMIDs:
None found

Sources:
PharmGKB

Interaction Types & Directionality:

n/a

PMIDs:
None found

Sources:
PharmGKB FDA

Interaction Types & Directionality:

n/a

PMIDs:
None found

Sources:
TTD

Interaction Types & Directionality:

n/a

PMIDs:
None found

Sources:
DTC

Alternate Names:

HKI-272 Development Name

NERATINIB Generic Name

Drug Info:

Drug Class Kinase Inhibitors

Drug Info:

Drug Indications antineoplastic agent

Drug Class Small molecule

FDA Approval not approved

Alternate Names:

CHEMBL180022 ChEMBL Drug ID

Alternate Names:

NERATINIB Primary Drug Name

NERATINIB Drug Generic Name

HKI-272 Drug Synonym

Alternate Names:

D0Q9CY TTD Drug ID