Drug Details

General Information of the Drug (ID: DR0749)
Name
Sunitinib
Synonyms
Sunitinibum; Sutent; PDGF TK antagonist; SU 11248; SU11248; KS-5022; SU-11248; SU-11248J; SU-12662; Su-011248; Sunitinib (INN); Sunitinib (free base); Sutent (TN); N-(2-diethylaminoethyl)-5-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide; N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide; 5-(5-FLUORO-2-OXO-1,2-DIHYDRO-INDOL-3-YLIDENEMETHYL)-2,4-DIMETHYL-1H-PYRROLE-3-CARBOXYLIC ACID (2-DIETHYLAMINO-ETHYL)-AMIDE; Sunitinib (Pan-TK inhibitor)
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Molecular Type
Small molecule
Disease Malignant digestive organ neoplasm [ICD-11: 2C11] Approved [1]
Structure
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2D MOL

3D MOL

ADMET Property
Clearance
The apparent oral clearance of drug is 34-62 L/h
Half-life
The concentration or amount of drug in body reduced by one-half in 40 - 60 hours
Metabolism
The drug is metabolized via the cytochrome P450 enzyme CYP3A4
Vd
The volume of distribution (Vd) of drug is 2230 L
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    Click to Show/Hide the Molecular Information and External Link(s) of This Natural Product
Formula
C22H27FN4O2
PubChem CID
5329102
Canonical SMILES
CCN(CC)CCNC(=O)C1=C(NC(=C1C)C=C2C3=C(C=CC(=C3)F)NC2=O)C
InChI
1S/C22H27FN4O2/c1-5-27(6-2)10-9-24-22(29)20-13(3)19(25-14(20)4)12-17-16-11-15(23)7-8-18(16)26-21(17)28/h7-8,11-12,25H,5-6,9-10H2,1-4H3,(H,24,29)(H,26,28)/b17-12-
InChIKey
WINHZLLDWRZWRT-ATVHPVEESA-N
CAS Number
CAS 557795-19-4
ChEBI ID
CHEBI:38940
GDSC
Sunitinib
TTD Drug ID
D0R0MW
DrugBank ID
DB01268
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Natural Product(s) Able to Enhance the Efficacy of This Drug
          Daunorubicin      Streptomyces peucetius     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
                    In-vitro Model MV4-11 CVCL_0064 Childhood acute monocytic leukemia Homo sapiens
Ba/F3 CVCL_0161 Healthy Mus musculus
MOLM-14 CVCL_7916 Adult acute myeloid leukemia Homo sapiens
                    Experimental
                    Result(s)		 The addition of potent FLT3 inhibitors such as SU11248 to AML chemotherapy regimens could result in improved treatment results.
          Gambogic acid      Garcinia morella     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 [3]
                    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 Expression CDKN1A  Molecule Info 
Pathway MAP
Down-regulation Expression VEGFA  Molecule Info 
Pathway MAP
                    In-vitro Model 786-O CVCL_1051 Renal cell carcinoma Homo sapiens
Caki-1 CVCL_0234 Clear cell renal cell carcinoma Homo sapiens
                    In-vivo Model Caki-1 cells (2x106) in 100 ul RPMI-1640 and 100 ul of matrigel were used to inject subcutaneously into each mouse (5-week-old male athymic BALB/c nu/nu mice).
                    Experimental
                    Result(s)		 The joint use of GA and SU can provide greater antitumor efficacy compared to either drug alone.
    β. A List of Natural Product(s) Able to Decrease the Adverse Effect of This Drug
          Curcumin      Hellenia speciosa     Click to Show/Hide the Molecular Data of This NP
                 Decreasing Adverse Drug Reaction     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [4]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression CDK1  Molecule Info 
Pathway MAP
Down-regulation Expression CDK4  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation RB1  Molecule Info 
Pathway MAP
                    In-vitro Model 786-O CVCL_1051 Renal cell carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Curcumin potentiates the ability of sunitinib to eliminate the VHL-lacking renal cancer cells 786-O.
Target and Pathway
Target(s) V-type proton ATPase subunit d 2  Molecule Info 
Vascular endothelial growth factor receptor 2 (KDR)  Molecule Info  [5]
KEGG Pathway Ras signaling pathway Click to Show/Hide
2 Rap1 signaling pathway
3 Cytokine-cytokine receptor interaction
4 Endocytosis
5 PI3K-Akt signaling pathway
6 VEGF signaling pathway
7 Focal adhesion
8 Proteoglycans in cancer
NetPath Pathway IL2 Signaling Pathway Click to Show/Hide
Panther Pathway Angiogenesis Click to Show/Hide
2 VEGF signaling pathway
Pathway Interaction Database HIF-2-alpha transcription factor network Click to Show/Hide
2 Beta3 integrin cell surface interactions
3 Signaling events mediated by TCPTP
4 SHP2 signaling
5 S1P1 pathway
6 VEGF and VEGFR signaling network
7 Integrins in angiogenesis
8 Signaling events mediated by VEGFR1 and VEGFR2
9 Notch-mediated HES/HEY network
Reactome Neurophilin interactions with VEGF and VEGFR Click to Show/Hide
2 VEGF binds to VEGFR leading to receptor dimerization
3 Integrin cell surface interactions
4 EPHA-mediated growth cone collapse
5 VEGFA-VEGFR2 Pathway
6 VEGFR2 mediated cell proliferation
WikiPathways Focal Adhesion Click to Show/Hide
2 Nifedipine Activity
3 Cardiac Progenitor Differentiation
4 Signaling by VEGF
5 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: 5713).
Reference 2 Synergistic effect of SU11248 with cytarabine or daunorubicin on FLT3 ITD-positive leukemic cells. Blood. 2004 Dec 15;104(13):4202-9.
Reference 3 Targeting renal cell carcinoma with gambogic acid in combination with sunitinib in vitro and in vivo. Asian Pac J Cancer Prev. 2012;13(12):6463-8.
Reference 4 Curcumin potentiates the ability of sunitinib to eliminate the VHL-lacking renal cancer cells 786-O: rapid inhibition of Rb phosphorylation as a preamble to cyclin D1 inhibition. Anticancer Agents Med Chem. 2013 Dec;13(10):1508-13.
Reference 5 2006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101.
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