Drug Details

General Information of the Drug (ID: DR5851)
Name
Dasatinib
Synonyms
Sprycel (TN); BMS 354825; BMS-354825; BMS-354825, Sprycel, BMS354825, Dasatinib; BMS354825; Dasatinib (USAN); Dasatinib [USAN]; Dasatinib anhydrous; Dasatinib, BMS 354825; Dasatinibum; Sprycel; Spyrcel
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Molecular Type
Small molecule
Disease Chronic myelogenous leukaemia [ICD-11: 2A20] 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
C22H26ClN7O2S
PubChem CID
3062316
Canonical SMILES
CC1=C(C(=CC=C1)Cl)NC(=O)C2=CN=C(S2)NC3=CC(=NC(=N3)C)N4CCN(CC4)CCO
InChI
1S/C22H26ClN7O2S/c1-14-4-3-5-16(23)20(14)28-21(32)17-13-24-22(33-17)27-18-12-19(26-15(2)25-18)30-8-6-29(7-9-30)10-11-31/h3-5,12-13,31H,6-11H2,1-2H3,(H,28,32)(H,24,25,26,27)
InChIKey
ZBNZXTGUTAYRHI-UHFFFAOYSA-N
CAS Number
CAS 302962-49-8
ChEBI ID
CHEBI:49375
GDSC
Dasatinib
TTD Drug ID
D0E6XR
DrugBank ID
DB01254
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Natural Product(s) Able to Enhance the Efficacy of This Drug
          Arsenic trioxide      Realgar and orpiment     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 ATF-4  Molecule Info 
Pathway MAP
Up-regulation Phosphorylation ATF2  Molecule Info 
Pathway MAP
Up-regulation Expression BBC3  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP9  Molecule Info 
Pathway MAP
Up-regulation Phosphorylation JNK1  Molecule Info 
Pathway MAP
Up-regulation Phosphorylation JUN  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
                    In-vitro Model SUP-B15 CVCL_0103 B acute lymphoblastic leukemia Homo sapiens
TOM-1 CVCL_1895 B acute lymphoblastic leukemia Homo sapiens
                    Experimental
                    Result(s)		 Combining ATO and Dasatinib leads to severe cell apoptosis by activating the UPR apoptotic IRE1/JNK/PUMA axis, while neutralizing the UPR ATF4-dependent anti-apoptotic axis, activated by ATO 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 [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vitro Model HCT 116 CVCL_0291 Colon carcinoma Homo sapiens
HT-29 CVCL_0320 Colon adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 The combinatorial therapy inhibited cellular growth, invasion and colonosphere formation and also reduced CSC population as evidenced by the decreased expression of CSC specific markers: CD133, CD44, CD166 and ALDH.
Target and Pathway
Target(s) Fusion protein Bcr-Abl (Bcr-Abl)  Molecule Info  [4]
Fyn tyrosine protein kinase (FYN)  Molecule Info  [4]
LCK tyrosine protein kinase (LCK)  Molecule Info  [4]
Proto-oncogene c-Src (SRC)  Molecule Info  [4]
KEGG Pathway ErbB signaling pathway Click to Show/Hide
2 Rap1 signaling pathway
3 Chemokine signaling pathway
4 Endocytosis
5 VEGF signaling pathway
6 Focal adhesion
7 Adherens junction
8 Tight junction
9 Gap junction
10 Platelet activation
11 GABAergic synapse
12 Inflammatory mediator regulation of TRP channels
13 Regulation of actin cytoskeleton
14 GnRH signaling pathway
15 Estrogen signaling pathway
16 Prolactin signaling pathway
17 Thyroid hormone signaling pathway
18 Oxytocin signaling pathway
19 Bacterial invasion of epithelial cells
20 Epithelial cell signaling in Helicobacter pylori infection
21 Shigellosis
22 Tuberculosis
23 Hepatitis B
24 Viral carcinogenesis
25 Proteoglycans in cancer
26 Sphingolipid signaling pathway
27 Axon guidance
28 Osteoclast differentiation
29 Natural killer cell mediated cytotoxicity
30 T cell receptor signaling pathway
31 Fc epsilon RI signaling pathway
32 Cholinergic synapse
33 Prion diseases
34 Pathogenic Escherichia coli infection
35 Measles
36 Viral myocarditis
37 NF-kappa B signaling pathway
38 HTLV-I infection
39 Primary immunodeficiency
NetPath Pathway IL2 Signaling Pathway Click to Show/Hide
2 TSH Signaling Pathway
3 TGF_beta_Receptor Signaling Pathway
4 TCR Signaling Pathway
Panther Pathway Angiogenesis Click to Show/Hide
2 Cadherin signaling pathway
3 Integrin signalling pathway
4 Parkinson disease
5 CCKR signaling map ST
6 Axon guidance mediated by semaphorins
7 T cell activation
Pathwhiz Pathway Fc Epsilon Receptor I Signaling in Mast Cells Click to Show/Hide
Pathway Interaction Database Endothelins Click to Show/Hide
2 Signaling events mediated by PRL
3 LPA receptor mediated events
4 Atypical NF-kappaB pathway
5 Glypican 1 network
6 Plasma membrane estrogen receptor signaling
7 Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met)
8 Signaling events mediated by PTP1B
9 S1P3 pathway
10 EPHB forward signaling
11 Nectin adhesion pathway
12 Regulation of p38-alpha and p38-beta
13 CDC42 signaling events
14 Signaling events regulated by Ret tyrosine kinase
15 Arf6 signaling events
16 Signaling events mediated by TCPTP
17 FAS (CD95) signaling pathway
18 Thromboxane A2 receptor signaling
19 Netrin-mediated signaling events
20 Alpha9 beta1 integrin signaling events
21 CXCR4-mediated signaling events
22 EGF receptor (ErbB1) signaling pathway
23 Class I PI3K signaling events
24 Posttranslational regulation of adherens junction stability and dissassembly
25 Regulation of Androgen receptor activity
26 E-cadherin signaling in the nascent adherens junction
27 amb2 Integrin signaling
28 Integrins in angiogenesis
29 ErbB1 downstream signaling
30 Urokinase-type plasminogen activator (uPA) and uPAR-mediated signaling
31 ErbB2/ErbB3 signaling events
32 EPHA forward signaling
33 E-cadherin signaling in keratinocytes
34 PDGFR-beta signaling pathway
35 Nongenotropic Androgen signaling
36 Internalization of ErbB1
37 CXCR3-mediated signaling events
38 Signaling events mediated by VEGFR1 and VEGFR2
39 Syndecan-2-mediated signaling events
40 Class I PI3K signaling events mediated by Akt
41 Syndecan-3-mediated signaling events
42 Ephrin B reverse signaling
43 Trk receptor signaling mediated by PI3K and PLC-gamma
44 EPHA2 forward signaling
45 Alpha-synuclein signaling
46 FGF signaling pathway
47 Alpha4 beta1 integrin signaling events
48 Signaling events mediated by focal adhesion kinase
49 Fc-epsilon receptor I signaling in mast cells
50 ErbB4 signaling events
51 TCR signaling in na&#xef
52
53 Ephrin A reverse signaling
54 Reelin signaling pathway
55 TCR signaling in na&#xef
56
57 Angiopoietin receptor Tie2-mediated signaling
58 IL2-mediated signaling events
59 Nephrin/Neph1 signaling in the kidney podocyte
60 IL12-mediated signaling events
61 SHP2 signaling
62 IL2 signaling events mediated by PI3K
63 IL2 signaling events mediated by STAT5
Reactome GPVI-mediated activation cascade Click to Show/Hide
2 PIP3 activates AKT signaling
3 Regulation of KIT signaling
4 Cell surface interactions at the vascular wall
5 FCGR activation
6 PECAM1 interactions
7 Constitutive Signaling by Aberrant PI3K in Cancer
8 DAP12 signaling
9 EPH-Ephrin signaling
10 Role of LAT2/NTAL/LAB on calcium mobilization
11 Nephrin interactions
12 NCAM signaling for neurite out-growth
13 CD28 co-stimulation
14 CD28 dependent PI3K/Akt signaling
15 CD28 dependent Vav1 pathway
16 CTLA4 inhibitory signaling
17 EPHB-mediated forward signaling
18 EPHA-mediated growth cone collapse
19 EPH-ephrin mediated repulsion of cells
20 CRMPs in Sema3A signaling
21 DCC mediated attractive signaling
22 Netrin mediated repulsion signals
23 VEGFA-VEGFR2 Pathway
24 Dectin-2 family
25 CD209 (DC-SIGN) signaling
26 RAF/MAP kinase cascade
27 Platelet Adhesion to exposed collagen
28 Regulation of signaling by CBL
29 Antigen activates B Cell Receptor (BCR) leading to generation of second messengers
30 Phosphorylation of CD3 and TCR zeta chains
31 Translocation of ZAP-70 to Immunological synapse
32 Generation of second messenger molecules
33 PD-1 signaling
34 Interleukin-2 signaling
WikiPathways ErbB Signaling Pathway Click to Show/Hide
2 Senescence and Autophagy in Cancer
3 Notch Signaling Pathway
4 EPO Receptor Signaling
5 EGF/EGFR Signaling Pathway
6 TGF beta Signaling Pathway
7 Signaling of Hepatocyte Growth Factor Receptor
8 Kit receptor signaling pathway
9 Pregnane X Receptor pathway
10 Aryl Hydrocarbon Receptor Pathway
11 IL-3 Signaling Pathway
12 Nanoparticle-mediated activation of receptor signaling
13 Polycystic Kidney Disease Pathway
14 Alpha 6 Beta 4 signaling pathway
15 BDNF signaling pathway
16 Integrated Pancreatic Cancer Pathway
17 Oncostatin M Signaling Pathway
18 Interleukin-11 Signaling Pathway
19 AGE/RAGE pathway
20 Signaling Pathways in Glioblastoma
21 TSLP Signaling Pathway
22 Arylhydrocarbon receptor (AhR) signaling pathway
23 Regulation of Microtubule Cytoskeleton
24 FSH signaling pathway
25 Leptin signaling pathway
26 RANKL/RANK Signaling Pathway
27 Integrin-mediated Cell Adhesion
28 Angiogenesis
29 Androgen receptor signaling pathway
30 TCR Signaling Pathway
31 Interferon type I signaling pathways
32 IL-2 Signaling Pathway
33 Ectoderm Differentiation
34 Fc epsilon receptor (FCERI) signaling
35 Signaling by the B Cell Receptor (BCR)
36 Signaling by SCF-KIT
37 DAP12 interactions
38 Host Interactions of HIV factors
39 PIP3 activates AKT signaling
40 T-Cell Receptor and Co-stimulatory Signaling
41 Primary Focal Segmental Glomerulosclerosis FSGS
42 B Cell Receptor Signaling Pathway
43 Pathogenic Escherichia coli infection
44 IL-7 Signaling Pathway
45 Semaphorin interactions
46 Platelet Adhesion to exposed collagen
47 Netrin-1 signaling
48 Nephrin interactions
49 NCAM signaling for neurite out-growth
50 GPVI-mediated activation cascade
51 Costimulation by the CD28 family
52 Cell surface interactions at the vascular wall
53 Inflammatory Response Pathway
54 TCR signaling
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: 5678).
Reference 2 Combination of arsenic trioxide and Dasatinib: a new strategy to treat Philadelphia chromosome-positive acute lymphoblastic leukaemia. J Cell Mol Med. 2018 Mar;22(3):1614-1626.
Reference 3 Combination of dasatinib and curcumin eliminates chemo-resistant colon cancer cells. J Mol Signal. 2011 Jul 20;6:7.
Reference 4 A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22.
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