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], [2]
Osteosarcoma	2B51	Phase 2	[1], [2]
Solid tumour/cancer	2A00-2F9Z	Phase 2	[1], [2]

• Therapeutic Class: Anticancer Agents
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 1:
  Molecular Weight (mw); 542
  Topological Polar Surface Area (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

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	[3]
Tyrosine-protein kinase ABL1 (ABL)	TT3PJMV	ABL1_HUMAN	Modulator	[3]

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

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] Current and future treatments of bone metastases. Expert Opin Emerg Drugs. 2008 Dec;13(4):609-27.
• [3] Novel dual Src/Abl inhibitors for hematologic and solid malignancies.Expert Opin Investig Drugs.2010 Aug;19(8):931-45.
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [5] 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.
• [6] Synthesis and Src kinase inhibitory activity of a series of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-furyl-3-quinolinecarbonitriles. J Med Chem. 2006 Dec 28;49(26):7868-76.
• [7] Targeted chronic myeloid leukemia therapy: Seeking a cure. Am J Health Syst Pharm. 2007 Dec 15;64(24 Suppl 15):S9-15.
• [8] Flumatinib, a selective inhibitor of BCR-ABL/PDGFR/KIT, effectively overcomes drug resistance of certain KIT mutants. Cancer Sci. 2014 Jan;105(1):117-25.
• [9] Company report (Deciphera Pharmaceuticals: Tumor-Targeted Programs and Indications)
• [10] Structure-based optimization of pyrazolo[3,4-d]pyrimidines as Abl inhibitors and antiproliferative agents toward human leukemia cell lines. J Med Chem. 2008 Mar 13;51(5):1252-9.
• [11] KW-2449, a novel multikinase inhibitor, suppresses the growth of leukemia cells with FLT3 mutations or T315I-mutated BCR/ABL translocation. Blood. 2009 Aug 20;114(8):1607-17.
• [12] Inhibitors of JAK-family kinases: an update on the patent literature 2013-2015, part 1.Expert Opin Ther Pat. 2017 Feb;27(2):127-143.
• [13] In vivo antitumor activity of herbimycin A, a tyrosine kinase inhibitor, targeted against BCR/ABL oncoprotein in mice bearing BCR/ABL-transfected cells. Leuk Res. 1994 Nov;18(11):867-73.
• [14] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [15] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [16] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [17] Clinical pipeline report, company report or official report of Turning Point Therapeutics.
• [18] The selectivity of protein kinase inhibitors: a further update. Biochem J. 2007 Dec 15;408(3):297-315.