ZORIFERTINIB

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C22H23ClFN5O3
Molecular Weight	459.901
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=CC2=C(C=C1OC(=O)N3CCN(C)C[C@H]3C)C(NC4=CC=CC(Cl)=C4F)=NC=N2

InChI

InChIKey=MXDSJQHFFDGFDK-CYBMUJFWSA-N

InChI=1S/C22H23ClFN5O3/c1-13-11-28(2)7-8-29(13)22(30)32-19-9-14-17(10-18(19)31-3)25-12-26-21(14)27-16-6-4-5-15(23)20(16)24/h4-6,9-10,12-13H,7-8,11H2,1-3H3,(H,25,26,27)/t13-/m1/s1

HIDE SMILES / InChI

Molecular Formula	C22H23ClFN5O3
Molecular Weight	459.901
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26313252 | https://www.ncbi.nlm.nih.gov/pubmed/27928026

AZD-3759 is an oral inhibitor of both wild-type and mutant EGFR with IC50 values in nanomolar range. The drug was discovered by AstraZeneca for the treatment of non-small-cell lung cancer with CNS metastases. AZD-3759 can penetrate the blood-brain barrier and was confirmed to be effective in vitro with NSCLC cell lines as well as in mouse model of brain metastases. AZD-3759 is currently in Phase 1 clinical trial.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Epidermal growth factor receptor 46 Target ID: CHEMBL2363049 Sources: https://www.ncbi.nlm.nih.gov/pubmed/29430654	Inhibitor 8297		102.0 nM [IC50]
Epidermal growth factor receptor 46 Target ID: P00533\|\|\|Q9GZX1 Gene ID: 1956.0 Gene Symbol: EGFR Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/26313252	Inhibitor 8297		0.28 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Non-small cell lung cancer 206 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27928026	Primary		Phase I 428	Unknown Approved Use Unknown

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
	inhibitor 1767	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C19 1478 CYP2C8 911 CYP1A2 1524 CYP3A4/5 278 OATP1B3 706 OATP1B1 788 OAT1 599 CYP2B6 810 BCRP 699 OAT3 642 P-gp 1461 OCT2 647	BCRP 561 P-gp 1537

Drug as perpetrator

Target	Modality	Activity
CYP1A2 1692	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/26313252/	no [IC50 >50 uM]
CYP2B6 1001	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/26313252/	no [IC50 >50 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/26313252/	no [IC50 >50 uM]
CYP2C8 965	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/26313252/	no [IC50 >50 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/26313252/	no [IC50 >50 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/26313252/	no [IC50 >50 uM]
CYP3A4/5 335	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/26313252/	no [IC50 >50 uM]
BCRP 773	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/26313252/	yes [IC50 1.7 uM]
OATP1B3 715	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/26313252/	yes [IC50 15 uM]
OAT3 644	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/26313252/	yes [IC50 18.5 uM]
OATP1B1 803	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/26313252/	yes [IC50 19.3 uM]
OCT2 648	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/26313252/	yes [IC50 24.7 uM]
OAT1 603	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/26313252/	yes [IC50 8.17 uM]
P-gp 1650	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/26313252/	yes [IC50 8.8 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
BCRP 561	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/26313252/	no
P-gp 1537	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/26313252/	no

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/26313252/

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P001TQK	https://www.1pchem.com/search?query=1P001TQK
AChemBlock	M15301	http://www.achemblock.com/catalogsearch/result/?q=M15301
AK Scientific	9479AL	https://aksci.com/item_detail.php?cat=9479AL
Ambeed	A171107	http://www.ambeed.com/search/Search.html?keyword=A171107
Angene	AGN-PC-0WAMIA	http://www.angenechemical.com/productshow/AGN-PC-0WAMIA.html
AstaTech	42354	http://astatechinc.com/CPSResult.php?CRNO=42354
Axon MedChem	2563	https://www.axonmedchem.com/product/2563
BLD Pharm	BD434982	http://www.bldpharm.com/search/Search.html?keyword=BD434982
BOC Sciences	1626387-80-1	http://www.bocsci.com/description.asp?cas=1626387-80-1
Cayman Chemical	19931	http://www.caymanchem.com/app/template/Product.vm/catalog/19931
Chem Scene	CS-5029	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-5029
ChemShuttle	134385	https://www.chemshuttle.com/catalogsearch/result/?q=134385
Combi-Blocks	QV-6716	http://www.combi-blocks.com/cgi-bin/find.cgi?QV-6716
KeyOrganics	AS-74755	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-74755
Lab Seeker	SC-A2036	http://www.labseeker.com/search.php?keywords=SC-A2036&category=0
Matrix Scientific	153968	http://www.matrixscientific.com/153968.html
MedChem Express	HY-18750	https://www.medchemexpress.com/search.html?q=HY-18750&ft=&fa=&fp=
MolPort	MolPort-042-665-890	https://www.molport.com/shop/molecule-link/MolPort-042-665-890
MolPort	MolPort-046-201-075	https://www.molport.com/shop/molecule-link/MolPort-046-201-075
Molnova	M12405	https://www.molnova.com/en/serch-list.html?keywords=M12405
Molnova	M18097	https://www.molnova.com/en/serch-list.html?keywords=M18097
Selleck Chemicals	S7971	http://www.selleckchem.com/search.html?searchDTO.searchParam=S7971
TargetMol	T3659	https://www.targetmol.com/search?keyword=T3659
TargetMol	T4249	https://www.targetmol.com/search?keyword=T4249
Toronto Research Chemicals	A808165	https://www.trc-canada.com/product-detail/?CatNum=A808165
Toronto Research Chemicals	H997603	https://www.trc-canada.com/product-detail/?CatNum=H997603
eMolecules	195316254	https://orderbb.emolecules.com/search/#?query=195316254
eMolecules	64016692	https://orderbb.emolecules.com/search/#?query=64016692
mcule	MCULE-1118702306	https://mcule.com/MCULE-1118702306/
mcule	MCULE-5418345924	https://mcule.com/MCULE-5418345924/
mcule	MCULE-9842364004	https://mcule.com/MCULE-9842364004/

PubMed

Title	Date	PubMed
Discovery and Evaluation of Clinical Candidate AZD3759, a Potent, Oral Active, Central Nervous System-Penetrant, Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor.	2015 Oct 22	26313252
AZD3759, a BBB-penetrating EGFR inhibitor for the treatment of EGFR mutant NSCLC with CNS metastases.	2016 Dec 7	27928026
Next-generation epidermal growth factor receptor tyrosine kinase inhibitors in epidermal growth factor receptor -mutant non-small cell lung cancer.	2016 Mar	26898616

Patents

Sample Use Guides

In Vivo Use Guide

AZD-3759 is given at a dose of 50 mg, administered twice daily, or 160 mag, administered once daily.

Route of Administration: Oral

In Vitro Use Guide

100 uL of NCI-H3255 (EGFR L858R), NCI-H838 (EGFR wild type) and PC-9 (Exon 19 deletion EGFR) cells were seeded in 96 well cell culture plates and incubated at 37C with 5% CO2 overnight and then treated with AZD-3759 at concentrations ranging from 10 to 0.0003 mM. IC50s for cellular inhibition of EGFR phosphorylation were 7.2, 64.5, 7.7 nM, respectively. In cellular proliferation assay, the cells were exposed to concentrations of compounds ranging from 30 to 0.0003 mM for 72 hours. GI50 values were 7, 21556 and 7.7 nM, respectively.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 11:19:44 GMT 2023` Edited by `admin` on `Sat Dec 16 11:19:44 GMT 2023`
Record UNII	67SX9H68W2
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

ZORIFERTINIB

Official Name

English

AZD-3759

Preferred Name

English

AZD3759

Code

English

1-PIPERAZINECARBOXYLIC ACID, 2,4-DIMETHYL-, 4-((3-CHLORO-2-FLUOROPHENYL)AMINO)-7-METHOXY-6-QUINAZOLINYL ESTER, (2R)-

Systematic Name

English

Zorifertinib [WHO-DD]

Common Name

English

zorifertinib [INN]

Common Name

English

Code System Code Type Description

DRUG BANK

DB14795