Details of the Drug

General Information of Drug (ID: DMAI95U)

Drug Name
PMID25656651-Compound-5
Indication
Disease Entry ICD 11 Status REF
Chronic myeloid leukaemia 2A20 Patented [1]
Affected Organisms
Humans and other mammals
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 1 Molecular Weight (mw) 532.6
Logarithm of the Partition Coefficient (xlogp) 4.1
Rotatable Bond Count (rotbonds) 6
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 8
Chemical Identifiers
Formula
C29H27F3N6O
IUPAC Name
3-(2-imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-N-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]benzamide
Canonical SMILES
CC1=C(C=C(C=C1)C(=O)NC2=CC(=C(C=C2)CN3CCN(CC3)C)C(F)(F)F)C#CC4=CN=C5N4N=CC=C5
InChI
InChI=1S/C29H27F3N6O/c1-20-5-6-22(16-21(20)8-10-25-18-33-27-4-3-11-34-38(25)27)28(39)35-24-9-7-23(26(17-24)29(30,31)32)19-37-14-12-36(2)13-15-37/h3-7,9,11,16-18H,12-15,19H2,1-2H3,(H,35,39)
InChIKey
PHXJVRSECIGDHY-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
24826799
ChEBI ID
CHEBI:78543
CAS Number
943319-70-8
UNII
4340891KFS
DrugBank ID
DB08901
TTD ID
D0WL1U
ACDINA ID
D00541
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug

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 Inhibitor [1]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Alanine aminotransferase 1 (GPT) OTOXOA0Q ALAT1_HUMAN Protein Interaction/Cellular Processes [2]
Angiopoietin-1 receptor (TEK) OT78YN57 TIE2_HUMAN Gene/Protein Processing [3]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Gene/Protein Processing [4]
Bcl-2-like protein 11 (BCL2L11) OTNQQWFJ B2L11_HUMAN Gene/Protein Processing [4]
BDNF/NT-3 growth factors receptor (NTRK2) OTD557PU NTRK2_HUMAN Gene/Protein Processing [5]
Breakpoint cluster region protein (BCR) OTCN76C1 BCR_HUMAN Post-Translational Modifications [5]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Protein Interaction/Cellular Processes [6]
Crk-like protein (CRKL) OTOYSD1R CRKL_HUMAN Post-Translational Modifications [7]
Cyclin-dependent kinase 4 (CDK4) OT7EP05T CDK4_HUMAN Gene/Protein Processing [4]
Cyclin-dependent kinase 6 (CDK6) OTR95N0X CDK6_HUMAN Gene/Protein Processing [4]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

References

1 Bcr-Abl tyrosine kinase inhibitors: a patent review.Expert Opin Ther Pat. 2015 Apr;25(4):397-412.
2 Cytotoxicity of 34 FDA approved small-molecule kinase inhibitors in primary rat and human hepatocytes. Toxicol Lett. 2018 Jul;291:138-148. doi: 10.1016/j.toxlet.2018.04.010. Epub 2018 Apr 12.
3 Discovery of 5-(arenethynyl) hetero-monocyclic derivatives as potent inhibitors of BCR-ABL including the T315I gatekeeper mutant. Bioorg Med Chem Lett. 2011 Jun 15;21(12):3743-8.
4 BET protein antagonist JQ1 is synergistically lethal with FLT3 tyrosine kinase inhibitor (TKI) and overcomes resistance to FLT3-TKI in AML cells expressing FLT-ITD. Mol Cancer Ther. 2014 Oct;13(10):2315-27. doi: 10.1158/1535-7163.MCT-14-0258. Epub 2014 Jul 22.
5 AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance. Cancer Cell. 2009 Nov 6;16(5):401-12. doi: 10.1016/j.ccr.2009.09.028.
6 Mechanisms of mitochondrial toxicity of the kinase inhibitors ponatinib, regorafenib and sorafenib in human hepatic HepG2 cells. Toxicology. 2018 Feb 15;395:34-44. doi: 10.1016/j.tox.2018.01.005. Epub 2018 Jan 16.
7 A multi-parameter in vitro screen in human stem cell-derived cardiomyocytes identifies ponatinib-induced structural and functional cardiac toxicity. Toxicol Sci. 2015 Jan;143(1):147-55. doi: 10.1093/toxsci/kfu215. Epub 2014 Oct 10.