Details of the Drug

General Information of Drug (ID: DMGYBZI)

Drug Name
PHA-739358
Synonyms Danusertib; PHA 739358; Danusertib, PHA-739358; (R)-N-(5-(2-methoxy-2-phenylacetyl)-1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazol-3-yl)-4-(4-methylpiperazin-1-yl)benzamide; 5-Amido-pyrrolopyrazole 9d
Indication
Disease Entry ICD 11 Status REF
Prostate cancer 2C82.0 Phase 2 [1]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 474.6
Logarithm of the Partition Coefficient (xlogp) 1.8
Rotatable Bond Count (rotbonds) 6
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 6
Chemical Identifiers
Formula
C26H30N6O3
IUPAC Name
N-[5-[(2R)-2-methoxy-2-phenylacetyl]-4,6-dihydro-1H-pyrrolo[3,4-c]pyrazol-3-yl]-4-(4-methylpiperazin-1-yl)benzamide
Canonical SMILES
CN1CCN(CC1)C2=CC=C(C=C2)C(=O)NC3=NNC4=C3CN(C4)C(=O)[C@@H](C5=CC=CC=C5)OC
InChI
InChI=1S/C26H30N6O3/c1-30-12-14-31(15-13-30)20-10-8-19(9-11-20)25(33)27-24-21-16-32(17-22(21)28-29-24)26(34)23(35-2)18-6-4-3-5-7-18/h3-11,23H,12-17H2,1-2H3,(H2,27,28,29,33)/t23-/m1/s1
InChIKey
XKFTZKGMDDZMJI-HSZRJFAPSA-N
Cross-matching ID
PubChem CID
11442891
ChEBI ID
CHEBI:94490
CAS Number
827318-97-8
DrugBank ID
DB11778
TTD ID
D02RJY
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
Aurora B messenger RNA (AURKB mRNA) TT9RTBL AURKB_HUMAN Inhibitor [2]
Aurora kinase A (AURKA) TTPS3C0 AURKA_HUMAN Inhibitor [3]
Aurora kinase B (AURKB) TT5LS6T AURKB_HUMAN Inhibitor [3]
Aurora kinase C (AURKC) TTLYXIT AURKC_HUMAN Inhibitor [2]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2) OTW8V2V1 ABCG2_HUMAN Drug Response [4]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Prostate cancer
ICD Disease Classification 2C82.0
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Aurora kinase A (AURKA) DTT AURKA 9.41E-46 -1.78 -2.05
Aurora kinase B (AURKB) DTT AURKB 3.52E-36 -0.82 -1.62
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: 7937).
2 Potent and selective Aurora inhibitors identified by the expansion of a novel scaffold for protein kinase inhibition. J Med Chem. 2005 Apr 21;48(8):3080-4.
3 Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
4 Abcg2 overexpression represents a novel mechanism for acquired resistance to the multi-kinase inhibitor Danusertib in BCR-ABL-positive cells in vitro. PLoS One. 2011 Apr 26;6(4):e19164. doi: 10.1371/journal.pone.0019164.