Drug Details

General Information of the Drug (ID: DR8223)
Name
AG1478
Synonyms
AG-1478; 153436-53-4; Tyrphostin AG 1478; N-(3-chlorophenyl)-6,7-dimethoxyquinazolin-4-amine; 175178-82-2; 4-(3-Chloroanilino)-6,7-dimethoxyquinazoline; AG1478; AG 1478; Tyrphostin AG-1478; 4-Quinazolinamine, N-(3-chlorophenyl)-6,7-dimethoxy-; AG-1478 (Tyrphostin AG-1478); tyrphostin AG1478; SUH0SEZ9HY; UNII-SUH0SEZ9HY; AG-1478 hydrochloride; CHEMBL7917; CHEBI:75404; N-(3-Chlorophenyl)-6,7-dimethoxy-4-quinazolinamine; NSC-693255; Tyrphostin AG-1478;NSC 693255; BRD6408; BRD-6408; SR-01000076156; NSC693255; PubChem22408; Tocris-1276; tyrphostin-AG-1478; AG-1478 free base; BiomolKI_000018; Maybridge1_004001; Lopac-T-4182; BiomolKI2_000028; DSSTox_CID_30044; CBiol_002058; DSSTox_GSID_51447; Lopac0_001127; Oprea1_653581; SCHEMBL93838; BSPBio_001390; KBioGR_000110; KBioSS_000110; cc-598; MLS006012026; PD153035 Analog 31; BDBM3532; GTPL4862; N-(3-chlorophenyl)-6,7-dimethoxy-quinazolin-4-amine; DTXSID0051447; BCBcMAP01_000035; HMS552N19; KBio2_000110; KBio2_002678; KBio2_005246; KBio3_000219; KBio3_000220; AOB2928; Bio1_000344; Bio1_000833; Bio1_001322; Bio2_000110; Bio2_000590; HMS1361F12; HMS1791F12; HMS1989F12; HMS3229O03; HMS3263B15; HMS3656B19; HMS3672E11; ZINC116937; BCP07988; BCP15152; EX-A1236; Tyrphostin AG 1478, >=98%; Tox21_303781; Tox21_501127; BBL101047; CCG-52663; MFCD00270914; s2728; STL554841; AKOS002350880; AG-1478 - Tyrphostin AG-1478; AG-1478/AG1478; CS-1606; LP01127; MCULE-8403703571; SB19361; SDCCGSBI-0051095.P003; VZ27727; IDI1_033860; NCGC00016017-01; NCGC00016017-02; NCGC00016017-03; NCGC00016017-04; NCGC00016017-05; NCGC00016017-06; NCGC00016017-07; NCGC00016017-08; NCGC00016017-09; NCGC00016017-20; NCGC00025093-01; NCGC00025093-02; NCGC00025093-03; NCGC00025093-04; NCGC00025093-05; NCGC00261812-01; NCGC00357072-01; AC-32828; AK-63142; GK 03499; HY-13524; NCI60_033425; SMR001456495; DB-026463; CAS-175178-82-2; EU-0101127; FT-0643504; FT-0643682; SW219714-1; EC-000.2540; 6,7-dimethoxy-4-(3'-chloroanilino)quinazoline; A24890; S-7703; T 4182; 11N-812; InSolution AG 1478 - CAS 175178-82-2; CU-00000000399-1; J-011074; J-519544; SR-01000076156-1; SR-01000076156-4; SR-01000076156-7; (3-Chlorophenyl)(6,7-dimethoxyquinazolin-4-yl)amine; AG 1478 - CAS 175178-82-2; BRD-K68336408-001-02-6; BRD-K68336408-003-02-2; Q27074338; COC1=C(OC)C=C2C(NC3=CC(Cl)=CC=C3)=NC=NC2=C1; 0TO
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Molecular Type
Small molecule
Disease Diabetic retinopathy [ICD-11: 9B71] Investigative [1]
Structure
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2D MOL

3D MOL

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Formula
C16H14ClN3O2
PubChem CID
2051
Canonical SMILES
COC1=C(C=C2C(=C1)C(=NC=N2)NC3=CC(=CC=C3)Cl)OC
InChI
1S/C16H14ClN3O2/c1-21-14-7-12-13(8-15(14)22-2)18-9-19-16(12)20-11-5-3-4-10(17)6-11/h3-9H,1-2H3,(H,18,19,20)
InChIKey
GFNNBHLJANVSQV-UHFFFAOYSA-N
CAS Number
CAS 153436-53-4
ChEBI ID
CHEBI:75404
TTD Drug ID
D0ZH1U
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Natural Product(s) Able to Enhance the Efficacy of This Drug
          Deguelin      Derris trifoliata     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression AKT1  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
                    In-vitro Model HSC-4 CVCL_1289 Tongue squamous cell carcinoma Homo sapiens
Ca9-22 CVCL_1102 Gingival squamous cell carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Deguelin Potentiates Apoptotic Activity of an EGFR Tyrosine Kinase Inhibitor (AG1478) in PIK3CA-Mutated Head and Neck Squamous Cell Carcinoma.
Target and Pathway
Target(s) Epidermal growth factor receptor (EGFR)  Molecule Info  [3]
Stress-activated protein kinase 2a (SAPK2A)  Molecule Info  [4]
KEGG Pathway MAPK signaling pathway Click to Show/Hide
2 ErbB signaling pathway
3 Ras signaling pathway
4 Rap1 signaling pathway
5 Calcium signaling pathway
6 Cytokine-cytokine receptor interaction
7 HIF-1 signaling pathway
8 FoxO signaling pathway
9 Endocytosis
10 PI3K-Akt signaling pathway
11 Dorso-ventral axis formation
12 Focal adhesion
13 Adherens junction
14 Gap junction
15 Regulation of actin cytoskeleton
16 GnRH signaling pathway
17 Estrogen signaling pathway
18 Oxytocin signaling pathway
19 Epithelial cell signaling in Helicobacter pylori infection
20 Hepatitis C
21 Pathways in cancer
22 Proteoglycans in cancer
23 MicroRNAs in cancer
24 Pancreatic cancer
25 Endometrial cancer
26 Glioma
27 Prostate cancer
28 Melanoma
29 Bladder cancer
30 Non-small cell lung cancer
31 Central carbon metabolism in cancer
32 Choline metabolism in cancer
33 Sphingolipid signaling pathway
34 Adrenergic signaling in cardiomyocytes
35 VEGF signaling pathway
36 Osteoclast differentiation
37 Signaling pathways regulating pluripotency of stem cells
38 Platelet activation
39 Toll-like receptor signaling pathway
40 NOD-like receptor signaling pathway
41 RIG-I-like receptor signaling pathway
42 T cell receptor signaling pathway
43 Fc epsilon RI signaling pathway
44 TNF signaling pathway
45 Leukocyte transendothelial migration
46 Neurotrophin signaling pathway
47 Retrograde endocannabinoid signaling
48 Dopaminergic synapse
49 Inflammatory mediator regulation of TRP channels
50 Progesterone-mediated oocyte maturation
51 Prolactin signaling pathway
52 Amyotrophic lateral sclerosis (ALS)
53 Shigellosis
54 Salmonella infection
55 Pertussis
56 Leishmaniasis
57 Chagas disease (American trypanosomiasis)
58 Toxoplasmosis
59 Tuberculosis
60 Influenza A
61 Epstein-Barr virus infection
NetPath Pathway IL4 Signaling Pathway Click to Show/Hide
2 EGFR1 Signaling Pathway
3 IL5 Signaling Pathway
4 FSH Signaling Pathway
5 TCR Signaling Pathway
Panther Pathway Cadherin signaling pathway Click to Show/Hide
2 EGF receptor signaling pathway
3 Alzheimer disease-amyloid secretase pathway
4 Angiogenesis
5 B cell activation
6 FGF signaling pathway
7 Interferon-gamma signaling pathway
8 Oxidative stress response
9 Parkinson disease
10 TGF-beta signaling pathway
11 Toll receptor signaling pathway
12 VEGF signaling pathway
13 Ras Pathway
14 p53 pathway feedback loops 2
15 p38 MAPK pathway
16 CCKR signaling map ST
Pathwhiz Pathway Fc Epsilon Receptor I Signaling in Mast Cells Click to Show/Hide
Pathway Interaction Database LPA receptor mediated events Click to Show/Hide
2 Signaling events mediated by PTP1B
3 Arf6 signaling events
4 Signaling events mediated by TCPTP
5 Thromboxane A2 receptor signaling
6 SHP2 signaling
7 Regulation of Telomerase
8 EGF receptor (ErbB1) signaling pathway
9 EGFR-dependent Endothelin signaling events
10 Posttranslational regulation of adherens junction stability and dissassembly
11 Direct p53 effectors
12 ErbB1 downstream signaling
13 Urokinase-type plasminogen activator (uPA) and uPAR-mediated signaling
14 E-cadherin signaling in keratinocytes
15 ErbB receptor signaling network
16 Internalization of ErbB1
17 Stabilization and expansion of the E-cadherin adherens junction
18 a6b1 and a6b4 Integrin signaling
19 Syndecan-3-mediated signaling events
20 Endothelins
21 BCR signaling pathway
22 p73 transcription factor network
23 p38 MAPK signaling pathway
24 Atypical NF-kappaB pathway
25 IL4-mediated signaling events
26 CD40/CD40L signaling
27 IL12-mediated signaling events
28 Regulation of p38-alpha and p38-beta
29 CDC42 signaling events
30 Angiopoietin receptor Tie2-mediated signaling
31 FAS (CD95) signaling pathway
32 Role of Calcineurin-dependent NFAT signaling in lymphocytes
33 Glucocorticoid receptor regulatory network
34 IL2-mediated signaling events
35 Rapid glucocorticoid signaling
36 Regulation of Androgen receptor activity
37 ATF-2 transcription factor network
38 IL6-mediated signaling events
39 p38 signaling mediated by MAPKAP kinases
40 Retinoic acid receptors-mediated signaling
41 CXCR3-mediated signaling events
42 Signaling mediated by p38-alpha and p38-beta
43 EPO signaling pathway
44 Signaling events mediated by VEGFR1 and VEGFR2
45 p53 pathway
46 S1P2 pathway
47 Trk receptor signaling mediated by the MAPK pathway
48 VEGFR3 signaling in lymphatic endothelium
49 FGF signaling pathway
50 RAC1 signaling pathway
51 Regulation of retinoblastoma protein
Reactome Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants Click to Show/Hide
2 SHC1 events in ERBB2 signaling
3 PLCG1 events in ERBB2 signaling
4 PIP3 activates AKT signaling
5 GRB2 events in EGFR signaling
6 GAB1 signalosome
7 SHC1 events in EGFR signaling
8 EGFR downregulation
9 GRB2 events in ERBB2 signaling
10 PI3K events in ERBB2 signaling
11 EGFR Transactivation by Gastrin
12 Constitutive Signaling by Aberrant PI3K in Cancer
13 Constitutive Signaling by EGFRvIII
14 RAF/MAP kinase cascade
15 NOD1/2 Signaling Pathway
16 p38MAPK events
17 ERK/MAPK targets
18 Activation of PPARGC1A (PGC-1alpha) by phosphorylation
19 Oxidative Stress Induced Senescence
20 CDO in myogenesis
21 DSCAM interactions
22 ADP signalling through P2Y purinoceptor 1
23 Platelet sensitization by LDL
24 VEGFA-VEGFR2 Pathway
25 activated TAK1 mediates p38 MAPK activation
26 Activation of the AP-1 family of transcription factors
27 KSRP (KHSRP) binds and destabilizes mRNA
WikiPathways ErbB Signaling Pathway Click to Show/Hide
2 Regulation of Actin Cytoskeleton
3 EGF/EGFR Signaling Pathway
4 MAPK Signaling Pathway
5 Focal Adhesion
6 Aryl Hydrocarbon Receptor Pathway
7 Extracellular vesicle-mediated signaling in recipient cells
8 TCA Cycle Nutrient Utilization and Invasiveness of Ovarian Cancer
9 Hair Follicle Development: Cytodifferentiation (Part 3 of 3)
10 Bladder Cancer
11 Hair Follicle Development: Induction (Part 1 of 3)
12 Signaling by ERBB4
13 Signaling by ERBB2
14 Gastrin-CREB signalling pathway via PKC and MAPK
15 PIP3 activates AKT signaling
16 Nanoparticle-mediated activation of receptor signaling
17 Aryl Hydrocarbon Receptor
18 Spinal Cord Injury
19 Integrated Pancreatic Cancer Pathway
20 Gastric cancer network 2
21 AGE/RAGE pathway
22 Signaling Pathways in Glioblastoma
23 Arylhydrocarbon receptor (AhR) signaling pathway
24 miR-targeted genes in muscle cell - TarBase
25 miR-targeted genes in lymphocytes - TarBase
26 miR-targeted genes in epithelium - TarBase
27 Integrated Breast Cancer Pathway
28 Signaling by EGFR
29 L1CAM interactions
30 Toll-like receptor signaling pathway
31 Monoamine Transport
32 Serotonin HTR1 Group and FOS Pathway
33 TCR Signaling Pathway
34 Senescence and Autophagy in Cancer
35 Interferon type I signaling pathways
36 Insulin Signaling
37 MAPK Cascade
38 Oxidative Stress
39 p38 MAPK Signaling Pathway
40 IL-4 Signaling Pathway
41 TGF beta Signaling Pathway
42 Kit receptor signaling pathway
43 Cardiac Hypertrophic Response
44 MAP kinase activation in TLR cascade
45 Regulation of mRNA Stability by Proteins that Bind AU-rich Elements
46 Structural Pathway of Interleukin 1 (IL-1)
47 JAK/STAT
48 Amyotrophic lateral sclerosis (ALS)
49 Alpha 6 Beta 4 signaling pathway
50 Cardiac Progenitor Differentiation
51 BDNF signaling pathway
52 Oncostatin M Signaling Pathway
53 Parkinsons Disease Pathway
54 Corticotropin-releasing hormone
55 B Cell Receptor Signaling Pathway
56 Prostate Cancer
57 TSLP Signaling Pathway
58 TWEAK Signaling Pathway
59 FSH signaling pathway
60 Leptin signaling pathway
61 RANKL/RANK Signaling Pathway
62 miR-targeted genes in leukocytes - TarBase
63 IL-1 signaling pathway
64 Signal amplification
65 Platelet homeostasis
66 NGF signalling via TRKA from the plasma membrane
67 Myogenesis
68 DSCAM interactions
69 MicroRNAs in cardiomyocyte hypertrophy
70 Angiogenesis
71 Physiological and Pathological Hypertrophy of the Heart
72 Regulation of toll-like receptor signaling pathway
References
Reference 1 EGFR inhibitor, AG1478, inhibits inflammatory infiltration and angiogenesis in mice with diabetic retinopathy. Clin Exp Pharmacol Physiol. 2019 Jan;46(1):75-85.
Reference 2 Deguelin Potentiates Apoptotic Activity of an EGFR Tyrosine Kinase Inhibitor (AG1478) in PIK3CA-Mutated Head and Neck Squamous Cell Carcinoma. Int J Mol Sci. 2017 Jan 26;18(2):262.
Reference 3 Use of a pharmacophore model for the design of EGFR tyrosine kinase inhibitors: isoflavones and 3-phenyl-4(1H)-quinolones. J Med Chem. 1999 Mar 25;42(6):1018-26.
Reference 4 Novel, potent and selective anilinoquinazoline and anilinopyrimidine inhibitors of p38 MAP kinase. Bioorg Med Chem Lett. 2004 Nov 1;14(21):5389-94.
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