Drug Details

General Information of the Drug (ID: DR4256)
Name
SU5416
Synonyms
Semaxanib; Semaxinib; SU 5416; 204005-46-9; Semoxind; Semaxanib (SU5416); SU-5416; 194413-58-6; TSU 16; Z-Semaxanib; UNII-71IA9S35AJ; VEGF Receptor 2 Kinase Inhibitor III; (Z)-3-((3,5-dimethyl-1H-pyrrol-2-yl)methylene)indolin-2-one; NSC-696819; (Z)-SU 5416; 71IA9S35AJ; CHEMBL276711; (3Z)-3-[(3,5-dimethyl-1H-pyrrol-2-yl)methylidene]-1H-indol-2-one; (3Z)-3-[(3,5-dimethyl-1H-pyrrol-2-yl)methylidene]-1,3-dihydro-2H-indol-2-one; 3-(1-(3,5-Dimethyl-1H-pyrrol-2-yl)meth-(Z)-ylidene)-2-oxo-2,3-dihydroindole; 3-((Z)-(3,5-Dimethylpyrrol-2-yl)methylene)-2-indolinone; Semaxnib; Sugen 5416; 3-[(3,5-dimethyl-1H-pyrrol-2-yl)methylidene]-1,3-dihydro-2H-indol-2-one; (3Z)-3-[(3,5-DIMETHYL-1H-PYRROL-2-YL)METHYLIDENE]-2,3-DIHYDRO-1H-INDOL-2-ONE; 3-[(2,4-Dimethylpyrrol-5-yl)methylidene]-indolin-2-one; SMR000568416; TSU-16; SR-01000076044; Semaxanib (USAN/INN); Semaxanib [USAN:INN]; methylene]-2H-indol-2-one; VEGFR2 Kinase Inhibitor III; 2H-Indol-2-one, 3-[(3,5-dimethyl-1H-pyrrol-2-yl)methylene]-1,3-dihydro-; NCGC00094381-03; 3-(2,4-dimethylpyrrol-5-yl)methylidene-indolin-2-one; NSC 696819; 2x2m; Semaxanib; SU5416; 1,3-Dihydro-3-[(3,5-dimethyl-1H-pyrrol-2-yl)methylene]-2H-indol-2-one; H-Indol-2-one, 3-((3,5-dimethyl-1H-pyrrol-2-yl)methylene)-1,3-dihydro-; S 8442; SCHEMBL8190; Lopac0_001110; SCHEMBL19571; 1,3-Dihydro-3-[(3,5-dimethyl-1H-pyrrol-2-yl); MLS001074896; MLS001332519; MLS001332520; BDBM4810; GTPL5056; QCR-86; 3-[(2,4-dimethylpyrrol-5-yl)methylidenyl]indolin-2-one; CHEBI:91083; cid_5329098; AOB6828; HMS2234L12; HMS3229O13; HMS3263M22; HMS3268J13; HMS3413H10; HMS3648O12; HMS3677H10; AMY10847; BCP06068; EX-A2158; Tox21 111271; Tox21_501110; 2033AH; 2712AH; HSCI1_000303; MFCD01940922; NSC696819; s2845; SU5146; ZINC12410091; 3-[(3,5-dimethyl-1h-pyrrol-2-yl)methylene]-1,3-dihydro-2h-indol-2-one; AKOS015994557; CCG-205186; CS-1225; DB06436; ES-0010; LP01110; SDCCGSBI-0051079.P003; NCGC00094381-01; NCGC00094381-02; NCGC00094381-04; NCGC00094381-05; NCGC00094381-19; NCGC00261795-01; HY-10374; QC-11357; SU005416; AB0094985; EU-0101110; SW219791-1; A12437; D05819; W-5403; 2H-Indol-2-one,5-dimethyl-2-pyrrolyl)methylene]-; J-013281; Q7449140; SR-01000076044-2; SR-01000076044-8; BRD-K63504947-001-05-5; 3-[(2,4-Dimethylpyrrol-5-yl)methylidenyl]-2-indolinon; 3-[(2,4-dimethylpyrrol-5-yl)methylidenyl]-2-indolinone; 3-[(2,4-dimethylpyrrol-5-yl)methylidenyl]-indolin-2-one; Semaxanib, Semoxind, TSU-16, NSC-696819, SU-5416; 3-[(3,5-Dimethyl-2H-pyrrol-2-ylidene)methyl]-1H-indol-2-ol; 3-[(3,5-Dimethyl-1H-pyrrol-2-yl)methylene]-1,3-dihydro- 2H-indol-2-one; 2H-Indol-2-one, 3-((3,5-dimethyl-1H-pyrrol-2-yl)methylene)-1,3-dihydro-, (3Z)-; 2H-Indol-2-one, 3-((3,5-dimethyl-1H-pyrrol-2-yl)methylene)-1,3-dihydro-, (Z)-; 2H-Indol-2-one, 3-(3,5-dimethyl-1H-pyrrol-2-yl)methylene)- 1,3-dihydro-, (Z)-; 3-[1-(3,5-dimethyl-1h-pyrrol-2-yl)-meth-(z)-ylidene]-2-oxo-2,3-dihydro-indole
    Click to Show/Hide
Molecular Type
Small molecule
Disease Thrombocytopenia [ICD-11: 3B64] Approved [1]
Structure
Click to Download Mol
2D MOL

3D MOL

    Click to Show/Hide the Molecular Information and External Link(s) of This Natural Product
Formula
C15H14N2O
PubChem CID
5329098
Canonical SMILES
CC1=CC(=C(N1)C=C2C3=CC=CC=C3NC2=O)C
InChI
1S/C15H14N2O/c1-9-7-10(2)16-14(9)8-12-11-5-3-4-6-13(11)17-15(12)18/h3-8,16H,1-2H3,(H,17,18)/b12-8-
InChIKey
WUWDLXZGHZSWQZ-WQLSENKSSA-N
CAS Number
CAS 194413-58-6
TTD Drug ID
D01PZD
DrugBank ID
DB06436
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Natural Product(s) Able to Enhance the Efficacy of This Drug
          Epigallocatechin gallate      Hamamelis virginiana     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 BCL-2  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
Down-regulation Expression CDK2  Molecule Info 
Pathway MAP
Up-regulation Expression CDKN1A  Molecule Info 
Pathway MAP
Down-regulation Expression EGFR  Molecule Info 
Pathway MAP
Down-regulation Expression FGF2  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
Down-regulation Expression VEGFA  Molecule Info 
Pathway MAP
                    In-vitro Model SH-SY5Y CVCL_0019 Neuroblastoma Homo sapiens
SK-N-BE(2) CVCL_0528 Neuroblastoma Homo sapiens
                    Experimental
                    Result(s)		 SU5416 and EGCG work synergistically and inhibit angiogenic and survival factors and induce cell cycle arrest to promote apoptosis in human malignant neuroblastoma SH-SY5Y and SK-N-BE2 cells.
Target and Pathway
Target(s) Aryl hydrocarbon receptor (AHR)  Molecule Info  [3]
Fibroblast growth factor receptor 1 (FGFR1)  Molecule Info  [4]
Platelet-derived growth factor receptor (PDGFR)  Molecule Info  [5]
Proto-oncogene c-Ret (RET)  Molecule Info  [6]
Thrombopoietin receptor (MPL)  Molecule Info  [7]
Tyrosine-protein kinase Kit (KIT)  Molecule Info  [8]
Vascular endothelial growth factor receptor 2 (KDR)  Molecule Info  [4]
KEGG Pathway MAPK signaling pathway Click to Show/Hide
2 Ras signaling pathway
3 Rap1 signaling pathway
4 PI3K-Akt signaling pathway
5 Adherens junction
6 Signaling pathways regulating pluripotency of stem cells
7 Regulation of actin cytoskeleton
8 Pathways in cancer
9 Proteoglycans in cancer
10 Prostate cancer
11 Melanoma
12 Central carbon metabolism in cancer
13 Cytokine-cytokine receptor interaction
14 Endocytosis
15 Hematopoietic cell lineage
16 Melanogenesis
17 Acute myeloid leukemia
18 Thyroid cancer
19 Jak-STAT signaling pathway
20 VEGF signaling pathway
21 Focal adhesion
NetPath Pathway TCR Signaling Pathway Click to Show/Hide
2 IL3 Signaling Pathway
3 IL4 Signaling Pathway
4 KitReceptor Signaling Pathway
5 IL2 Signaling Pathway
Panther Pathway Angiogenesis Click to Show/Hide
2 FGF signaling pathway
3 VEGF signaling pathway
Pathway Interaction Database Glypican 1 network Click to Show/Hide
2 Syndecan-4-mediated signaling events
3 N-cadherin signaling events
4 FGF signaling pathway
5 C-MYB transcription factor network
6 Signaling events mediated by Stem cell factor receptor (c-Kit)
7 Signaling events regulated by Ret tyrosine kinase
8 Posttranslational regulation of adherens junction stability and dissassembly
9 HIF-2-alpha transcription factor network
10 Beta3 integrin cell surface interactions
11 Signaling events mediated by TCPTP
12 SHP2 signaling
13 S1P1 pathway
14 VEGF and VEGFR signaling network
15 Integrins in angiogenesis
16 Signaling events mediated by VEGFR1 and VEGFR2
17 Notch-mediated HES/HEY network
Reactome PIP3 activates AKT signaling Click to Show/Hide
2 Regulation of KIT signaling
3 Constitutive Signaling by Aberrant PI3K in Cancer
4 RAF/MAP kinase cascade
5 Neurophilin interactions with VEGF and VEGFR
6 VEGF binds to VEGFR leading to receptor dimerization
7 Integrin cell surface interactions
8 EPHA-mediated growth cone collapse
9 VEGFA-VEGFR2 Pathway
10 VEGFR2 mediated cell proliferation
WikiPathways Regulation of Actin Cytoskeleton Click to Show/Hide
2 Endochondral Ossification
3 MAPK Signaling Pathway
4 Mesodermal Commitment Pathway
5 Hair Follicle Development: Induction (Part 1 of 3)
6 Integrated Pancreatic Cancer Pathway
7 Signaling Pathways in Glioblastoma
8 Neural Crest Differentiation
9 Signaling by FGFR
10 Kit receptor signaling pathway
11 Differentiation Pathway
12 Signaling by SCF-KIT
13 PIP3 activates AKT signaling
14 Cardiac Progenitor Differentiation
15 miR-targeted genes in muscle cell - TarBase
16 miR-targeted genes in lymphocytes - TarBase
17 miR-targeted genes in epithelium - TarBase
18 SIDS Susceptibility Pathways
19 Dopaminergic Neurogenesis
20 Platelet Aggregation (Plug Formation)
21 Focal Adhesion
22 Nifedipine Activity
23 Signaling by VEGF
24 Angiogenesis
References
Reference 1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6974).
Reference 2 SU5416 and EGCG work synergistically and inhibit angiogenic and survival factors and induce cell cycle arrest to promote apoptosis in human malignant neuroblastoma SH-SY5Y and SK-N-BE2 cells. Neurochem Res. 2011 Aug;36(8):1383-96.
Reference 3 A Phase I study of the angiogenesis inhibitor SU5416 (semaxanib) in solid tumours, incorporating dynamic contrast MR pharmacodynamic end points. Br J Cancer. 2005 Oct 17;93(8):876-83.
Reference 4 Anthranilic acid amides: a novel class of antiangiogenic VEGF receptor kinase inhibitors. J Med Chem. 2002 Dec 19;45(26):5687-93.
Reference 5 Discovery of 5-[5-fluoro-2-oxo-1,2- dihydroindol-(3Z)-ylidenemethyl]-2,4- dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)amide, a novel... J Med Chem. 2003 Mar 27;46(7):1116-9.
Reference 6 Synthesis, structure-activity relationship and crystallographic studies of 3-substituted indolin-2-one RET inhibitors. Bioorg Med Chem. 2010 Feb 15;18(4):1482-96.
Reference 7 2008 FDA drug approvals. Nat Rev Drug Discov. 2009 Feb;8(2):93-6.
Reference 8 New anilinophthalazines as potent and orally well absorbed inhibitors of the VEGF receptor tyrosine kinases useful as antagonists of tumor-driven a... J Med Chem. 2000 Jun 15;43(12):2310-23.
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link