Details of the Drug

General Information of Drug (ID: DMBLHGP)

Drug Name
Saracatinib
Synonyms H8H; AZD-0530; Saracatinib, AZD-0530, AZD0530; N-(5-Chloro-1,3-benzodioxol-4-yl)-7-(2-(4-methylpiperazin-1-yl)ethoxy)-5-(tetrahydro-2H-pyran-4-yloxy)quinazolin-4-amine
Indication
Disease Entry ICD 11 Status REF
Hematologic tumour 2B33.Y Phase 2 [1]
Metastatic colorectal cancer 2B91 Phase 2 [2]
Osteosarcoma 2B51 Phase 2 [1]
Solid tumour/cancer 2A00-2F9Z Phase 2 [1]
Middle East Respiratory Syndrome (MERS) 1D64 Investigative [3]
Therapeutic Class
Anticancer Agents
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 1 Molecular Weight (mw) 542
Logarithm of the Partition Coefficient (xlogp) 4.1
Rotatable Bond Count (rotbonds) 8
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 10
Chemical Identifiers
Formula
C27H32ClN5O5
IUPAC Name
N-(5-chloro-1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5-(oxan-4-yloxy)quinazolin-4-amine
Canonical SMILES
CN1CCN(CC1)CCOC2=CC3=C(C(=C2)OC4CCOCC4)C(=NC=N3)NC5=C(C=CC6=C5OCO6)Cl
InChI
InChI=1S/C27H32ClN5O5/c1-32-6-8-33(9-7-32)10-13-35-19-14-21-24(23(15-19)38-18-4-11-34-12-5-18)27(30-16-29-21)31-25-20(28)2-3-22-26(25)37-17-36-22/h2-3,14-16,18H,4-13,17H2,1H3,(H,29,30,31)
InChIKey
OUKYUETWWIPKQR-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
10302451
CAS Number
379231-04-6
DrugBank ID
DB11805
TTD ID
D0M0XB
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Proto-oncogene c-Src (SRC) TT6PKBN SRC_HUMAN Modulator [4]
Tyrosine-protein kinase ABL1 (ABL) TT3PJMV ABL1_HUMAN Modulator [4]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Cytochrome P450 1A2 (CYP1A2) OTLLBX48 CP1A2_HUMAN Biotransformations [5]
Cytochrome P450 2D6 (CYP2D6) OTZJC802 CP2D6_HUMAN Biotransformations [5]
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Biotransformations [5]
Cytochrome P450 7A1 (CYP7A1) OT8Z5KLD CP7A1_HUMAN Gene/Protein Processing [6]
Membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase (PKMYT1) OTYRXD2T PMYT1_HUMAN Gene/Protein Processing [7]
Neural cell adhesion molecule L1 (L1CAM) OTNWAQ4Y L1CAM_HUMAN Post-Translational Modifications [8]
Tyrosine-protein kinase CSK (CSK) OTP03OD0 CSK_HUMAN Gene/Protein Processing [6]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Hematologic tumour
ICD Disease Classification 2B33.Y
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Proto-oncogene c-Src (SRC) DTT SRC 7.46E-03 -0.2 -1.24
Tyrosine-protein kinase ABL1 (ABL) DTT ABL1 6.28E-04 0.33 2.07
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

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: 7731).
2 Phase II Study of Saracatinib (AZD0530) in Patients With Previously Treated Metastatic Colorectal Cancer. Invest New Drugs. 2015 Aug;33(4):977-84.
3 Saracatinib Inhibits Middle East Respiratory Syndrome-Coronavirus Replication In Vitro. Viruses. 2018 May 24;10(6). pii: E283.
4 Novel dual Src/Abl inhibitors for hematologic and solid malignancies.Expert Opin Investig Drugs.2010 Aug;19(8):931-45.
5 Cytochrome P450 Mediated Bioactivation of Saracatinib. Chem Res Toxicol. 2016 Nov 21;29(11):1835-1842. doi: 10.1021/acs.chemrestox.6b00242. Epub 2016 Nov 3.
6 A novel bile acid-activated vitamin D receptor signaling in human hepatocytes. Mol Endocrinol. 2010 Jun;24(6):1151-64.
7 Identification of PKMYT1 inhibitors by screening the GSK published protein kinase inhibitor set I and II. Bioorg Med Chem. 2018 Aug 7;26(14):4014-4024. doi: 10.1016/j.bmc.2018.06.027. Epub 2018 Jun 20.
8 L1 coupling to ankyrin and the spectrin-actin cytoskeleton modulates ethanol inhibition of L1 adhesion and ethanol teratogenesis. FASEB J. 2018 Mar;32(3):1364-1374. doi: 10.1096/fj.201700970. Epub 2018 Jan 3.