PELITINIB

Details

Stereochemistry	ACHIRAL
Molecular Formula	C24H23ClFN5O2
Molecular Weight	467.923
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCOC1=C(NC(=O)\C=C\CN(C)C)C=C2C(=C1)N=CC(C#N)=C2NC3=CC(Cl)=C(F)C=C3

InChI

InChIKey=WVUNYSQLFKLYNI-AATRIKPKSA-N

InChI=1S/C24H23ClFN5O2/c1-4-33-22-12-20-17(11-21(22)30-23(32)6-5-9-31(2)3)24(15(13-27)14-28-20)29-16-7-8-19(26)18(25)10-16/h5-8,10-12,14H,4,9H2,1-3H3,(H,28,29)(H,30,32)/b6-5+

HIDE SMILES / InChI

Molecular Formula	C24H23ClFN5O2
Molecular Weight	467.923
Charge	0
Count

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

Description
Sources: https://ayurajan.blogspot.ru/2015/09/drugs-in-clinical-pipeline-pelitinib.html
Curator's Comment: description was created based on several sources, including: http://adisinsight.springer.com/drugs/800014700 | http://www.pharmacodia.com/yaodu/html/v1/chemicals/417346143631ba772ccbbb20c6c4151b.html | https://www.wikigenes.org/e/chem/e/6445562.html | https://www.cancer.gov/publications/dictionaries/cancer-drug?cdrid=352165

Pelitinib (EKB-569) is a 3-cyanoquinoline pan-ErbB tyrosine kinase inhibitor with potential antineoplastic activity. Pelitinib irreversibly binds covalently to epidermal growth factor receptors, thereby inhibiting receptor phosphorylation and signal transduction and resulting in apoptosis and suppression of proliferation in tumor cells that overexpress these receptors. Pelitinib had been in phase II clinical trials for the treatment of non-small cell lung cancer and colorectal cancer. Treatment-emergent adverse events were diarrhea, abdominal pain, gastrointestinal carcinoma, intestinal obstruction and vomiting.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Epidermal growth factor receptor erbB1 58 Target ID: CHEMBL203 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12502359	Inhibitor 8297	0.08 µM [IC50]
Receptor protein-tyrosine kinase erbB-2 35 Target ID: CHEMBL1824 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12502359	Inhibitor 8297	1.23 µM [IC50]
Tyrosine-protein kinase SRC 19 Target ID: CHEMBL267 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10973323	Inhibitor 8297	282.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Non-small cell lung cancer 206 Sources: https://clinicaltrials.gov/ct2/show/NCT00067548 http://adisinsight.springer.com/drugs/800014700 http://www.pharmacodia.com/yaodu/html/v1/chemicals/417346143631ba772ccbbb20c6c4151b.html	Primary	Phase II 1132	Unknown Approved Use Unknown
Colorectal cancer 101 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18765554 https://www.ncbi.nlm.nih.gov/pubmed/18172273	Primary	Phase II 1132	Unknown Approved Use Unknown
Solid tumors 145 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16710023	Primary	Phase I 428	Unknown Approved Use Unknown

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
activator 80	inhibitor 1767	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
BCRP 699 P-gp 1461		BCRP 75 P-gp 257

Drug as perpetrator

Target	Modality	Activity
CYP2D6 1891	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645840#sid=363677203	inconclusive [IC50 23.9185 uM]
CYP3A4 1925	activator 214 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645841#sid=363677203	no [EC50 2.1317 uM]
BCRP 773	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/25988710/	no
P-gp 1650	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/25988710/	no
CYP2C9 1819	inhibitor 3277	yes [IC50 3.7908 uM]
BCRP 773	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/25988710/	yes
P-gp 1650	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/25988710/	yes

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY110755	https://www.001chemical.com/chem/search?q=DY110755
1PlusChem LLC	1P007MFZ	https://www.1pchem.com/search?query=1P007MFZ
A2B Chem	AD54879	http://a2bchem.com/prod/AD54879
AChemBlock	10360	http://www.achemblock.com/catalogsearch/result/?q=10360
AK Scientific	X7489	https://aksci.com/item_detail.php?cat=X7489
Ambeed	A111899	http://www.ambeed.com/search/Search.html?keyword=A111899
ApexBio Technology	A1835	https://www.apexbt.com/catalogsearch/result/?q=A1835
AstaTech	41112	http://astatechinc.com/CPSResult.php?CRNO=41112
Axon MedChem	1665	https://www.axonmedchem.com/product/1665
BOC Sciences	257933-82-7	http://www.bocsci.com/description.asp?cas=257933-82-7
BioSynth	Q-101404	https://www.biosynth.com/en/products/life-science/other-biochemicals/products/Q-101404
Capot Chemical	25889	https://www.capotchem.com/search.do?q=25889
Cayman Chemical	15627	http://www.caymanchem.com/app/template/Product.vm/catalog/15627
Chem Scene	CS-0037	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0037
ChemShuttle	101088	https://www.chemshuttle.com/catalogsearch/result/?q=101088
Debye Scientific	DB-068677	https://www.debyesci.com/index.php?id=product&ext[cno]=DB-068677
Excenen	EX-A061	http://www.excenen.com/searchresultlist.php?id=EX-A061
Exclusive Chemistry	2259	http://www.exchemistry.com/chem-catalog/product-2259.html
Hairui	HR139042	http://www.hairuichem.com/en/product/search.do?q=HR139042
KeyOrganics	AS-16280	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-16280
Lab Seeker	SC-87072	http://www.labseeker.com/search.php?keywords=SC-87072&category=0
LabSeeker	SC-87072	http://www.labseeker.com/search.php?keywords=SC-87072&category=0
Matrix Scientific	143584	http://www.matrixscientific.com/143584.html
MedChem Express	HY-32718	https://www.medchemexpress.com/search.html?q=HY-32718&ft=&fa=&fp=
MolPort	MolPort-006-395-626	https://www.molport.com/shop/molecule-link/MolPort-006-395-626
Molcore	MC110755	http://www.molcore.com/CatMC110755.html
Molnova	M13779	https://www.molnova.com/en/serch-list.html?keywords=M13779
MuseChem	R046027	https://www.musechem.com/product/R046027.html
Ryan Scientific	Rilpivirine	https://ryansci.com/products?q=Rilpivirine&list_q=&search_type=exact
ShangHai Biochempartner	BCP000331	http://www.biochempartner.com/search_BCP000331
ShangHai Biochempartner	BCP02376	http://www.biochempartner.com/search_BCP02376
TargetMol	T2327	https://www.targetmol.com/search?keyword=T2327
Tetrahedron	TS72189	http://www.thsci.com/search.do?q=TS72189
Toronto Research Chemicals	P218700	https://www.trc-canada.com/product-detail/?CatNum=P218700
eMolecules	26950823	https://orderbb.emolecules.com/search/#?query=26950823
eMolecules	48855813	https://orderbb.emolecules.com/search/#?query=48855813
eMolecules	50524298	https://orderbb.emolecules.com/search/#?query=50524298
eNovation Chemicals	D497616	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D497616&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-5537729917	https://mcule.com/MCULE-5537729917/
mcule	MCULE-7049448183	https://mcule.com/MCULE-7049448183/

PubMed

Title	Date	PubMed
		252160345
Syntheses and EGFR kinase inhibitory activity of 6-substituted-4-anilino [1,7] and [1,8] naphthyridine-3-carbonitriles.	2004 Mar 22	15006373
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.	2007 Jun 1	17416531
Irreversible EGFR inhibitor EKB-569 targets low-LET γ-radiation-triggered rel orchestration and potentiates cell death in squamous cell carcinoma.	2011	22242139
Cysteine mapping in conformationally distinct kinase nucleotide binding sites: application to the design of selective covalent inhibitors.	2011 Mar 10	21322567

Patents

Sample Use Guides

In Vivo Use Guide

The maximum tolerated dose of EKB-569 is 75 mg once-daily.

Route of Administration: Oral

In Vitro Use Guide

Pelitinib has been found to exert a potent anti-proliferative activity against tumor cells overexpressing EGF-R, including NHEK, A431 and MDA-468 cells, with IC50 values of 61 nM, 125 nM and 260 nM respectively; while it has also been found to potently inhibit EGF-induced phosphorylated EGF-R (pEGF-R) in A431 and NHEK cells with IC50 values ranging from 20 nM to 80 nM.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:28:46 GMT 2023` Edited by `admin` on `Fri Dec 15 15:28:46 GMT 2023`
Record UNII	X5DWL380Z6
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

PELITINIB

Official Name

English

EKB-569

Code

English

pelitinib [INN]

Common Name

English

WAY-EKB-569

Code

English

Pelitinib [WHO-DD]

Common Name

English

2-BUTENAMIDE, N-(4-((3-CHLORO-4-FLUOROPHENYL)AMINO)-3-CYANO-7-ETHOXY-6-QUINOLINYL)-4-(DIMETHYLAMINO)-, (2E)-

Systematic Name

English

(2E)-N-(-((3-CHLORO-4-FLUOROPHENYL)AMINO)3-CYANO-7-ETHOXYQUINOLIN-6-YL)-4-(DIMETHYLAMINO)BUT-2-ENAMIDE

Systematic Name

English

PELITINIB [USAN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C2167