Details of the Drug

General Information of Drug (ID: DMWA74Y)

• Drug Name: Radotinib
• Synonyms: IY-5511; IY-GV50205; Anticancer, Il-yang

Indication

Disease Entry	ICD 11	Status	REF
leukaemia	2A60-2B33	Phase 3	[1], [2]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 1:
  Molecular Weight (mw); 530.5
  Topological Polar Surface Area (xlogp); 3.9
  Rotatable Bond Count (rotbonds); 6
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 10
• Chemical Identifiers:
  Formula: C27H21F3N8O
  IUPAC Name: 4-methyl-N-[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl]-3-[(4-pyrazin-2-ylpyrimidin-2-yl)amino]benzamide
  Canonical SMILES: CC1=C(C=C(C=C1)C(=O)NC2=CC(=CC(=C2)C(F)(F)F)N3C=C(N=C3)C)NC4=NC=CC(=N4)C5=NC=CN=C5
  InChI: InChI=1S/C27H21F3N8O/c1-16-3-4-18(9-23(16)37-26-33-6-5-22(36-26)24-13-31-7-8-32-24)25(39)35-20-10-19(27(28,29)30)11-21(12-20)38-14-17(2)34-15-38/h3-15H,1-2H3,(H,35,39)(H,33,36,37)
  InChIKey: DUPWHXBITIZIKZ-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 16063245
  CAS Number: 926037-48-1
  DrugBank ID: DB12323
  TTD ID: D01NIR

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Fusion protein Bcr-Abl (Bcr-Abl)	TTS7G69	BCR_HUMAN-ABL1_HUMAN	Modulator	[3]

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: 7814).
• [2] ClinicalTrials.gov (NCT01511289) Radotinib Versus Imatinib in Newly Diagnosed Philadelphia Chromosome and Chronic Myeloid Leukemia Chronic Phase Patients. U.S. National Institutes of Health.
• [3] Danusertib, an aurora kinase inhibitor.Expert Opin Investig Drugs.2012 Mar;21(3):383-93.
• [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.
• [5] 2007 FDA drug approvals: a year of flux. Nat Rev Drug Discov. 2008 Feb;7(2):107-9.
• [6] ABL001, a Potent Allosteric Inhibitor of BCR-ABL, Prevents Emergence of Resistant Disease When Administered in Combination with Nilotinib in an in Vivo Murine Model of Chronic Myeloid Leukemia, NorthBuilding, 2014, 120-125.
• [7] Asciminib in Chronic Myeloid Leukemia after ABL Kinase Inhibitor Failure. N Engl J Med. 2019 Dec 12;381(24):2315-2326.
• [8] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [9] Design, synthesis and preclinical evaluation of NRC-AN-019. Int J Oncol. 2013 Jan;42(1):168-78.
• [10] Preclinical development of HQP1351, a multikinase inhibitor targeting a broad spectrum of mutant KIT kinases, for the treatment of imatinib-resistant gastrointestinal stromal tumors. Cell Biosci. 2019 Oct 26;9:88.
• [11] NPB001-05 inhibits Bcr-Abl kinase leading to apoptosis of imatinib-resistant cells. Front Biosci (Elite Ed). 2011 Jun 1;3:1273-88.
• [12] Effects of the Bcr/abl kinase inhibitors STI571 and adaphostin (NSC 680410) on chronic myelogenous leukemia cells in vitro. Blood. 2002 Jan 15;99(2):664-71.