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
CHEMBL1171837
CAS Number
943319-70-8
UNII
4340891KFS
DrugBank ID
DB08901
TTD ID
D0WL1U
ACDINA ID
D00541
Drug-Molecule Activity Atlas (DMA)NEW Click to Jump to the Detailed DMA Information of This Drug
Drug Pharmacogenomic Perturbation (DPP)NEW Click to Jump to the Detailed DPP Information of This Drug
Drug ADMET Endpoint Profile (DAE)NEW Click to Jump to the Detailed DAE Information of This Drug
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
Bcl-2-like protein 11 (BCL2L11) OTNQQWFJ B2L11_HUMAN Gene/Protein Processing [2]
Crk-like protein (CRKL) OTOYSD1R CRKL_HUMAN Post-Translational Modifications [3]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Gene/Protein Processing [2]
Cytoplasmic tyrosine-protein kinase BMX (BMX) OTJUE0ZD BMX_HUMAN Gene/Protein Processing [4]
High affinity nerve growth factor receptor (NTRK1) OTJORQAU NTRK1_HUMAN Gene/Protein Processing [4]
Mast/stem cell growth factor receptor Kit (KIT) OTHUY3VZ KIT_HUMAN Gene/Protein Processing [4]
Microtubule-associated proteins 1A/1B light chain 3A (MAP1LC3A) OTPMGIU4 MLP3A_HUMAN Post-Translational Modifications [5]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Post-Translational Modifications [6]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Post-Translational Modifications [6]
Myc proto-oncogene protein (MYC) OTPV5LUK MYC_HUMAN Gene/Protein Processing [2]
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 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.
3 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.
4 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.
5 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.
6 Ponatinib may overcome resistance of FLT3-ITD harbouring additional point mutations, notably the previously refractory F691I mutation. Br J Haematol. 2012 May;157(4):483-92. doi: 10.1111/j.1365-2141.2012.09085.x. Epub 2012 Mar 13.