AZD3759 - Moligand™, ≥99% , Epidermal growth factor receptor erbB1 inhibitor, CAS No.1626387-80-1, Epidermal growth factor receptor erbB1 inhibitor

CAS: 1626387-80-1 Cat. No.: A413895 Molecular Weight: 459.9

GRADE & PURITY Moligand™, ≥99%

Synonyms

(R)-4-(3-chloro-2-fluorophenylamino)-7-methoxyquinazolin-6-yl 2,4-dimethylpiperazine-1-carboxylate | EX-A720 | zorifertinib | (9S,10R)-3,4,5,14,15,16-hexamethoxy-9,10-dimethyltricyclo[10.4.0.0^{2,7}]hexadeca-1(16),2,4,6,12,14-hexaene | 4-((3-Chloro-2-fluo

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

Overview

Information

AZD3759 is a potent, oral active, CNS-penetrantEGFRinhibitor withIC50of 0.3 nM, 0.2 nM, and 0.2 nM for EGFR (WT), EGFR (L858R), and EGFR (exon 19Del), respectively. Phase 1.

Targets

EGFR (L858R) (Cell-free assay); EGFR (exon 19Del) (Cell-free assay); EGFR (WT) (Cell-free assay) 0.2 nM; 0.2 nM; 0.3 nM

In vitro

In H3255 (L858R) cells, AZD3759 inhibits EGFR phosphorylation with IC50 of 7.2 nM. AZD3759 demonstrates inhibitory effects on both the pEGFR pathway and cell proliferation of EGFR mutation-derived cells PC-9 and H3255 with IC50 of 7.7 nM and 7 nM, respectively, showing mo activity on cell proliferation of H838 cells.

In vivo

AZD3759 shows good oral bioavailability in dogs, and penetrates extensively into monkey brain. In a brain metastasis PC-9 (Exon19Del) model, AZD3759 (15 mg/kg) causes significant dose-dependent antitumor efficacy.

Cell Research(from reference)

Cell lines：PC-9 (exon 19Del), H3255 (L858R) and H838 (wt) cells 

Concentrations：~30 mM 

Incubation Time：72 h 

Specifications

Synonyms

(R)-4-(3-chloro-2-fluorophenylamino)-7-methoxyquinazolin-6-yl 2, 4-dimethylpiperazine-1-carboxylate | EX-A720 | zorifertinib | (9S, 10R)-3, 4, 5, 14, 15, 16-hexamethoxy-9, 10-dimethyltricyclo[10.4.0.0^{2, 7}]hexadeca-1(16), 2, 4, 6, 12, 14-hexaene | 4-((3-Chloro-2-fluo

Specifications & Purity

Moligand™, ≥99%

Biochemical and Physiological Mechanisms

AZD3759 is a potent, oral active, CNS-penetrant EGFR inhibitor with IC50 of 0.3 nM, 0.2 nM, and 0.2 nM for EGFR (WT), EGFR (L858R), and EGFR (exon 19Del), respectively. Phase 1.

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

This product requires cold chain shipping. Ground and other economy services are not available.

Grade

Moligand™

Action Type

INHIBITOR

Mechanism of action

Epidermal growth factor receptor erbB1 inhibitor

Purity

≥99%

Product Properties

• ALogP: 4.635
• hba_count: 5
• HBD Count: 1
• Rotatable Bond: 5

Names and Identifiers

• Pubchem Sid: 488202379
• Pubchem Sid Url: https://pubchem.ncbi.nlm.nih.gov/substance/488202379
• Canonical Smiles: CC1CN(CCN1C(=O)OC2=C(C=C3C(=C2)C(=NC=N3)NC4=C(C(=CC=C4)Cl)F)OC)C
• IUPAC Name: [4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl] (2R)-2,4-dimethylpiperazine-1-carboxylate
• 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
• Isomeric SMILES: C[C@@H]1CN(CCN1C(=O)OC2=C(C=C3C(=C2)C(=NC=N3)NC4=C(C(=CC=C4)Cl)F)OC)C
• Molecular Weight: 459.9
• Reaxy-Rn: 27160017
• Reaxys-RN_link_address: https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=27160017&ln=

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organoheterocyclic compounds
    • Class Diazanaphthalenes
      • Subclass Benzodiazines
        • Level5 Quinazolines
          • Level6 Quinazolinamines

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• Class: Diazanaphthalenes
• Subclass: Benzodiazines
• Intermediate Tree Nodes: Quinazolines
• Direct Parent: Quinazolinamines
• Alternative Parents: Piperazine carboxylic acids Aniline and substituted anilines Anisoles Alkyl aryl ethers Aminopyrimidines and derivatives N-methylpiperazines Chlorobenzenes Fluorobenzenes Aryl chlorides Aryl fluorides Imidolactams Carbamate esters Heteroaromatic compounds Trialkylamines Azacyclic compounds Carbonyl compounds Organofluorides Organic oxides Organochlorides Hydrocarbon derivatives
• Molecular Framework: Aromatic heteropolycyclic compounds
• Substituents: Quinazolinamine - Piperazine-1-carboxylic acid - Anisole - Aniline or substituted anilines - Phenol ether - Alkyl aryl ether - Aminopyrimidine - Fluorobenzene - Halobenzene - Chlorobenzene - N-alkylpiperazine - N-methylpiperazine - Aryl chloride - 1,4-diazinane - Monocyclic benzene moiety - Aryl halide - Aryl fluoride - Imidolactam - Pyrimidine - Piperazine - Benzenoid - Heteroaromatic compound - Carbamic acid ester - Tertiary amine - Tertiary aliphatic amine - Ether - Azacycle - Organic nitrogen compound - Organohalogen compound - Organochloride - Carbonyl group - Organofluoride - Organonitrogen compound - Organooxygen compound - Hydrocarbon derivative - Organic oxide - Organic oxygen compound - Amine - Aromatic heteropolycyclic compound
• Description: This compound belongs to the class of organic compounds known as quinazolinamines. These are heterocyclic aromatic compounds containing a quianazoline moiety substituted by one or more amine groups.
• External Descriptors: Not available

Data sources

1. Djoumbou Feunang Y, Eisner R, Knox C, Chepelev L, Hastings J, Owen G, Fahy E, Steinbeck C, Subramanian S, Bolton E, Greiner R, and Wishart DS. ClassyFire: Automated Chemical Classification With A Comprehensive, Computable Taxonomy. Journal of Cheminformatics, 2016, 8:61.

DOI: 10.1186/s13321-016-0174-y

Associated Targets(Human)

EGFR Tclin Epidermal growth factor receptor (4 Activities)

Discover Target: EGFR

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

KCNH2 Tclin Potassium voltage-gated channel subfamily H member 2 (0 Activities)

Discover Target: KCNH2

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

EGFR Tclin Epidermal growth factor receptor erbB1 (33727 Activities)

Discover Target: EGFR

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

DRD2 Tclin Dopamine D2 receptor (23596 Activities)

Discover Target: DRD2

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

LCK Tclin Tyrosine-protein kinase LCK (9212 Activities)

Discover Target: LCK

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

CYP2C8 Tchem Cytochrome P450 2C8 (1492 Activities)

Discover Target: CYP2C8

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

SRC Tclin Tyrosine-protein kinase SRC (10310 Activities)

Discover Target: SRC

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

FLT1 Tclin Vascular endothelial growth factor receptor 1 (6262 Activities)

Discover Target: FLT1

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

KDR Tclin Vascular endothelial growth factor receptor 2 (20924 Activities)

Discover Target: KDR

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

CYP2D6 Tclin Cytochrome P450 2D6 (33882 Activities)

Discover Target: CYP2D6

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

FYN Tclin Tyrosine-protein kinase FYN (5308 Activities)

Discover Target: FYN

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

LYN Tclin Tyrosine-protein kinase Lyn (4251 Activities)

Discover Target: LYN

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

CYP1A2 Tchem Cytochrome P450 1A2 (26471 Activities)

Discover Target: CYP1A2

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

CYP3A5 Tclin Cytochrome P450 3A5 (525 Activities)

Discover Target: CYP3A5

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

CYP2C9 Tchem Cytochrome P450 2C9 (32119 Activities)

Discover Target: CYP2C9

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

CYP2C19 Tchem Cytochrome P450 2C19 (29246 Activities)

Discover Target: CYP2C19

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

CYP3A4 Tclin Cytochrome P450 3A4 (53859 Activities)

Discover Target: CYP3A4

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

YES1 Tclin Tyrosine-protein kinase YES (2781 Activities)

Discover Target: YES1

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

CYP2B6 Tchem Cytochrome P450 2B6 (1338 Activities)

Discover Target: CYP2B6

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

NCI-H1975 (4994 Activities)

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Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

A549 (127892 Activities)

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Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

A-431 (6446 Activities)

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Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

PC-9 (1037 Activities)

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Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

EPHB4 Tchem Ephrin type-B receptor 4 (3198 Activities)

Discover Target: EPHB4

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

NCI-H838 (81 Activities)

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Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

ERBB2 Tclin Epidermal growth factor receptor (487 Activities)

Discover Target: ERBB2

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

BEAS-2B (690 Activities)

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Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

HCC827 (1172 Activities)

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Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

NCI-H3255 (70 Activities)

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Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Associated Targets(non-human)

Hdac6 Histone deacetylase 6 (222 Activities)

Discover Target: Hdac6

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Canis familiaris (36305 Activities)

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Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Mus musculus (284745 Activities)

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Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Rattus norvegicus (775804 Activities)

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Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

rep Replicase polyprotein 1ab (378 Activities)

Discover Target: rep

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Brain (1 Activities)

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Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Blood (6 Activities)

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Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Plasma (328 Activities)

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Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Cerebrospinal fluid (288 Activities)

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Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Mechanisms of Action

Chemical and Physical Properties

• Solubility: Solubility (25°C) In vitro DMSO: 92 mg/mL (200.04 mM); Ethanol: 44 mg/mL warmed with 50ºC Water: bath (95.67 mM); Water: Insoluble
• DMSO(mg / mL) Max Solubility: 91
• DMSO(mM) Max Solubility: 197.869102
• Water(mg / mL) Max Solubility: ＜1
• Molecular Weight: 459.900 g/mol
• XLogP3: 4.100
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 8
• Rotatable Bond Count: 5
• Exact Mass: 459.147 Da
• Monoisotopic Mass: 459.147 Da
• Topological Polar Surface Area: 79.800 Ų
• Heavy Atom Count: 32
• Formal Charge: 0
• Complexity: 649.000
• Isotope Atom Count: 0
• Defined Atom Stereocenter Count: 1
• Undefined Atom Stereocenter Count: 0
• Defined Bond Stereocenter Count: 0
• Undefined Bond Stereocenter Count: 0
• The total count of all stereochemical bonds: 0
• Covalently-Bonded Unit Count: 1