U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C26H31ClN6O2
Molecular Weight 495.016
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of NAZARTINIB

SMILES

CN(C)C\C=C\C(=O)N1CCCC[C@H](C1)N2C(NC(=O)C3=CC=NC(C)=C3)=NC4=C2C(Cl)=CC=C4

InChI

InChIKey=IOMMMLWIABWRKL-WUTDNEBXSA-N
InChI=1S/C26H31ClN6O2/c1-18-16-19(12-13-28-18)25(35)30-26-29-22-10-6-9-21(27)24(22)33(26)20-8-4-5-15-32(17-20)23(34)11-7-14-31(2)3/h6-7,9-13,16,20H,4-5,8,14-15,17H2,1-3H3,(H,29,30,35)/b11-7+/t20-/m1/s1

HIDE SMILES / InChI

Molecular Formula C26H31ClN6O2
Molecular Weight 495.016
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 1
Optical Activity UNSPECIFIED

Novartis Oncology (previously Novartis) is developing nazartinib (formerly EGF 816), a third generation mutant-selective tyrosine kinase inhibitor (TKI) of epidermal growth factor receptor (EGFR), for the treatment of solid malignancies, with a focus on non-small cell lung cancer. Nazartinib is a covalent mutant-selective EGFR inhibitor, with Ki and Kinact of 31 nM and 0.222 min−1 on EGFR(L858R/790M) mutant, respectively. Upon oral administration, nazartinib covalently binds to and inhibits the activity of mutant forms of EGFR, including the T790M EGFR mutant, thereby preventing EGFR-mediated signaling. This may both induce cell death and inhibit tumor growth in EGFR-overexpressing tumor cells. EGFR, a receptor tyrosine kinase mutated in many tumor cell types, plays a key role in tumor cell proliferation and tumor vascularization. EGF816 preferentially inhibits mutated forms of EGFR including T790M, a secondarily acquired resistance mutation, and may have therapeutic benefits in tumors with T790M-mediated resistance when compared to other EGFR tyrosine kinase inhibitors. As this agent is selective towards mutant forms of EGFR, its toxicity profile may be reduced as compared to non-selective EGFR inhibitors which also inhibit wild-type EGFR.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
25.0 nM [IC50]
160.6 nM [IC50]
PubMed

PubMed

TitleDatePubMed

Sample Use Guides

Advanced EGFR-mutant NSCLC: patients received the recommended phase II oral dose of 150 mg once daily on a continuous schedule.
Route of Administration: Oral
Nazartinib (EGF816) shows potent inhibition of pEGFR levels in H3255, HCC827, and H1975 cell lines with EC50 values of 5, 1, and 3 nM, respectively. Nazartinib inhibits cell proliferation, with EC50 values of 9, 11, and 25 nM in H3255, HCC827, and H1975, respectively. Nazartinib has an OC50 (compound concentration at 50% occupancy) value of 2 and 5 nM on HCC827 and H1975, respectively.
Substance Class Chemical
Created
by admin
on Sat Dec 16 07:55:37 GMT 2023
Edited
by admin
on Sat Dec 16 07:55:37 GMT 2023
Record UNII
KE7K32EME8
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
NAZARTINIB
INN   WHO-DD  
USAN   INN  
Official Name English
N-(7-Chloro-1-{(3R)-1-[(2E)-4-(dimethylamino)but-2-enoyl]azepan-3-yl}-1H-benzimidazol-2-yl)-2-methylpyridine-4-carboxamide
Systematic Name English
EGF-816
Code English
EGF816 [WHO-DD]
Common Name English
NVP-EGF816-NX
Code English
NAZARTINIB [USAN]
Common Name English
4-PYRIDINECARBOXAMIDE, N-(7-CHLORO-1-((3R)-1-((2E)-4-(DIMETHYLAMINO)-1-OXO-2-BUTEN-1-YL)HEXAHYDRO-1H-AZEPIN-3-YL)-1H-BENZIMIDAZOL-2-YL)-2-METHYL-
Systematic Name English
N-(7-CHLORO-1-((3R)-1-((2E)-4-(DIMETHYLAMINO) BUT-2-ENOYL)AZEPAN-3-YL)-1HBENZIMIDAZOLOL-2-YL)-2-METHYLPYRIDINE-4-CARBOXAMIDE
Systematic Name English
nazartinib [INN]
Common Name English
Nazartinib [WHO-DD]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C129825
Created by admin on Sat Dec 16 07:55:37 GMT 2023 , Edited by admin on Sat Dec 16 07:55:37 GMT 2023
NCI_THESAURUS C2167
Created by admin on Sat Dec 16 07:55:37 GMT 2023 , Edited by admin on Sat Dec 16 07:55:37 GMT 2023
Code System Code Type Description
NCI_THESAURUS
C115109
Created by admin on Sat Dec 16 07:55:37 GMT 2023 , Edited by admin on Sat Dec 16 07:55:37 GMT 2023
PRIMARY
SMS_ID
100000172087
Created by admin on Sat Dec 16 07:55:37 GMT 2023 , Edited by admin on Sat Dec 16 07:55:37 GMT 2023
PRIMARY
FDA UNII
KE7K32EME8
Created by admin on Sat Dec 16 07:55:37 GMT 2023 , Edited by admin on Sat Dec 16 07:55:37 GMT 2023
PRIMARY
INN
10259
Created by admin on Sat Dec 16 07:55:37 GMT 2023 , Edited by admin on Sat Dec 16 07:55:37 GMT 2023
PRIMARY
CAS
1508250-71-2
Created by admin on Sat Dec 16 07:55:37 GMT 2023 , Edited by admin on Sat Dec 16 07:55:37 GMT 2023
PRIMARY
ChEMBL
CHEMBL3545234
Created by admin on Sat Dec 16 07:55:37 GMT 2023 , Edited by admin on Sat Dec 16 07:55:37 GMT 2023
PRIMARY
PUBCHEM
72703790
Created by admin on Sat Dec 16 07:55:37 GMT 2023 , Edited by admin on Sat Dec 16 07:55:37 GMT 2023
PRIMARY
USAN
FG-100
Created by admin on Sat Dec 16 07:55:37 GMT 2023 , Edited by admin on Sat Dec 16 07:55:37 GMT 2023
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
TARGET -> INHIBITOR
Related Record Type Details
ACTIVE MOIETY