Drug Information

Drug General Information
Drug ID
D0Q9CY
Former ID
DCL000346
Drug Name
HKI-272
Synonyms
Neratinib (ERBB2 inhibitor)
Drug Type
Small molecular drug
Indication Breast cancer [ICD9: 174, 175; ICD10:C50] Phase 3 [1]
Therapeutic Class
Anticancer Agents
Company
Wyeth Research
Structure
Download
2D MOL

3D MOL
Formula
C30H29ClN6O3
Canonical SMILES
CCOC1=C(C=C2C(=C1)N=CC(=C2NC3=CC(=C(C=C3)OCC4=CC=CC=N4)<br />Cl)C#N)NC(=O)C=CCN(C)C
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
PubChem Compound ID
9915743
PubChem Substance ID
14886227, 24194959, 45987396, 76593408, 96025633, 103441767, 104048227, 104253482, 109693540, 121277958, 123055351, 124757612, 124950160, 125164416, 126665957, 126731400, 131477696, 134342020, 134964338, 135252601, 135727425, 136348728, 136367583, 136367864, 137006066, 139363252, 143497501, 144116272, 152186746, 152234948, 152258784, 152344179, 160647635, 162011383, 162037785, 162200061, 163883153, 164041890, 172914303, 174530425, 177748696, 178102313, 180371634, 185978452, 198962615, 223381071, 223471413, 223679237, 226878157, 226878158
Target and Pathway
Target(s) Vascular endothelial growth factor receptor 2 Target Info Inhibitor [2]
mRNA of HER2 Target Info Inhibitor [3]
Epidermal growth factor receptor Target Info Inhibitor [2]
Receptor protein-tyrosine kinase erbB-2 Target Info Inhibitor [4]
KEGG Pathway Ras signaling pathway
Rap1 signaling pathway
Cytokine-cytokine receptor interaction
Endocytosis
PI3K-Akt signaling pathway
VEGF signaling pathway
Focal adhesion
Proteoglycans in cancerhsa04012:ErbB signaling pathway
Calcium signaling pathway
HIF-1 signaling pathway
Adherens junction
Pathways in cancer
Proteoglycans in cancer
MicroRNAs in cancer
Pancreatic cancer
Endometrial cancer
Prostate cancer
Bladder cancer
Non-small cell lung cancer
Central carbon metabolism in cancerhsa04010:MAPK signaling pathway
ErbB signaling pathway
FoxO signaling pathway
Dorso-ventral axis formation
Gap junction
Regulation of actin cytoskeleton
GnRH signaling pathway
Estrogen signaling pathway
Oxytocin signaling pathway
Epithelial cell signaling in Helicobacter pylori infection
Hepatitis C
Glioma
Melanoma
Central carbon metabolism in cancer
Choline metabolism in cancerhsa04012:ErbB signaling pathway
NetPath Pathway IL2 Signaling PathwayNetPath_11:TCR Signaling PathwayNetPath_16:IL4 Signaling Pathway
EGFR1 Signaling PathwayNetPath_11:TCR Signaling Pathway
PANTHER Pathway Angiogenesis
VEGF signaling pathwayP00012:Cadherin signaling pathway
EGF receptor signaling pathwayP00012:Cadherin signaling pathway
EGF receptor signaling pathway
Pathway Interaction Database HIF-2-alpha transcription factor network
Beta3 integrin cell surface interactions
Signaling events mediated by TCPTP
SHP2 signaling
S1P1 pathway
VEGF and VEGFR signaling network
Integrins in angiogenesis
Signaling events mediated by VEGFR1 and VEGFR2
Notch-mediated HES/HEY networkerbb4_pathway:ErbB4 signaling events
ErbB2/ErbB3 signaling events
ErbB receptor signaling network
a6b1 and a6b4 Integrin signaling
Validated targets of C-MYC transcriptional repressionlysophospholipid_pathway:LPA receptor mediated events
Signaling events mediated by PTP1B
Arf6 signaling events
Thromboxane A2 receptor signaling
Regulation of Telomerase
EGF receptor (ErbB1) signaling pathway
EGFR-dependent Endothelin signaling events
Posttranslational regulation of adherens junction stability and dissassembly
Direct p53 effectors
ErbB1 downstream signaling
Urokinase-type plasminogen activator (uPA) and uPAR-mediated signaling
E-cadherin signaling in keratinocytes
Internalization of ErbB1
Stabilization and expansion of the E-cadherin adherens junction
Syndecan-3-mediated signaling eventserbb4_pathway:ErbB4 signaling events
Validated targets of C-MYC transcriptional repression
PathWhiz Pathway Phosphatidylinositol Phosphate MetabolismPW000168:Phosphatidylinositol Phosphate Metabolism
Reactome Neurophilin interactions with VEGF and VEGFR
VEGF binds to VEGFR leading to receptor dimerization
Integrin cell surface interactions
EPHA-mediated growth cone collapse
VEGFA-VEGFR2 Pathway
VEGFR2 mediated cell proliferationR-HSA-1250196:SHC1 events in ERBB2 signaling
PLCG1 events in ERBB2 signaling
PIP3 activates AKT signaling
GRB2 events in ERBB2 signaling
PI3K events in ERBB2 signaling
Constitutive Signaling by Aberrant PI3K in Cancer
Sema4D induced cell migration and growth-cone collapse
RAF/MAP kinase cascadeR-HSA-1236382:Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants
SHC1 events in ERBB2 signaling
GRB2 events in EGFR signaling
GAB1 signalosome
SHC1 events in EGFR signaling
EGFR downregulation
EGFR Transactivation by Gastrin
Constitutive Signaling by EGFRvIII
RAF/MAP kinase cascadeR-HSA-1250196:SHC1 events in ERBB2 signaling
RAF/MAP kinase cascade
WikiPathways Focal Adhesion
Nifedipine Activity
Cardiac Progenitor Differentiation
Signaling by VEGF
AngiogenesisWP710:DNA Damage Response (only ATM dependent)
ErbB Signaling Pathway
EGF/EGFR Signaling Pathway
Extracellular vesicle-mediated signaling in recipient cells
Bladder Cancer
Signaling by ERBB2
Integrated Pancreatic Cancer Pathway
Signaling Pathways in Glioblastoma
Leptin signaling pathway
miR-targeted genes in muscle cell - TarBase
Semaphorin interactionsWP673:ErbB Signaling Pathway
Regulation of Actin Cytoskeleton
MAPK Signaling Pathway
Aryl Hydrocarbon Receptor Pathway
TCA Cycle Nutrient Utilization and Invasiveness of Ovarian Cancer
Hair Follicle Development: Cytodifferentiation (Part 3 of 3)
Hair Follicle Development: Induction (Part 1 of 3)
Signaling by ERBB4
Gastrin-CREB signalling pathway via PKC and MAPK
PIP3 activates AKT signaling
Nanoparticle-mediated activation of receptor signaling
Aryl Hydrocarbon Receptor
Spinal Cord Injury
Gastric cancer network 2
AGE/RAGE pathway
Arylhydrocarbon receptor (AhR) signaling pathway
miR-targeted genes in lymphocytes - TarBase
miR-targeted genes in epithelium - TarBase
Integrated Breast Cancer Pathway
Signaling by EGFR
L1CAM interactionsWP710:DNA Damage Response (only ATM dependent)
Semaphorin interactions
References
REF 1Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800021154)
REF 2Bioorg Med Chem. 2007 Jun 1;15(11):3635-48. Epub 2007 Mar 23.Dual irreversible kinase inhibitors: quinazoline-based inhibitors incorporating two independent reactive centers with each targeting different cysteine residues in the kinase domains of EGFR and VEGFR-2.
REF 3Proc Natl Acad Sci U S A. 2007 Dec 11;104(50):19936-41. Epub 2007 Dec 6.Identification of genotype-correlated sensitivity to selective kinase inhibitors by using high-throughput tumor cell line profiling.
REF 4A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22.

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