Details of the Drug

General Information of Drug (ID: DMYISJK)

• Drug Name: PX-866
• Synonyms: Sonolisib; PX-866; CHEBI:65345; 502632-66-8; PX866; UNII-987796874T; PX 866; 987796874T; (4S,4aR,5R,6aS,9aR,E)-1-((diallylamino)methylene)-11-hydroxy-4-(methoxymethyl)-4a,6a-dimethyl-2,7,10-trioxo-1,2,4,4a,5,6,6a,7,8,9,9a,10-dodecahydroindeno[4,5-h]isochromen-5-yl acetate; (1E,4S,4aR,5R,6aS,9aR)-1-{[di(prop-2-en-1-yl)amino]methylidene}-11-hydroxy-4-(methoxymethyl)-4a,6a-dimethyl-2,7,10-trioxo-1,2,4,4a,5,6,6a,7,8,9,9a,10-dodecahydroindeno[4,5-h]isochromen-5-yl acetate; Sonolisib [INN]; GTPL7941; CHEMBL411907

Indication

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Phase 2	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 1:
  Molecular Weight (mw); 525.6
  Logarithm of the Partition Coefficient (xlogp); 1.7
  Rotatable Bond Count (rotbonds); 9
  Hydrogen Bond Donor Count (hbonddonor); 1
  Hydrogen Bond Acceptor Count (hbondacc); 9
• Chemical Identifiers:
  Formula: C29H35NO8
  IUPAC Name: [(3aR,6E,9S,9aR,10R,11aS)-6-[[bis(prop-2-enyl)amino]methylidene]-5-hydroxy-9-(methoxymethyl)-9a,11a-dimethyl-1,4,7-trioxo-2,3,3a,9,10,11-hexahydroindeno[4,5-h]isochromen-10-yl] acetate
  Canonical SMILES: CC(=O)O[C@@H]1C[C@]2([C@@H](CCC2=O)C3=C1[C@]4([C@H](OC(=O)/C(=C/N(CC=C)CC=C)/C4=C(C3=O)O)COC)C)C
  InChI: InChI=1S/C29H35NO8/c1-7-11-30(12-8-2)14-17-23-26(34)25(33)22-18-9-10-20(32)28(18,4)13-19(37-16(3)31)24(22)29(23,5)21(15-36-6)38-27(17)35/h7-8,14,18-19,21,34H,1-2,9-13,15H2,3-6H3/b17-14+/t18-,19+,21+,28-,29-/m0/s1
  InChIKey: QIUASFSNWYMDFS-NILGECQDSA-N
• Cross-matching ID:
  PubChem CID: 9849735
  ChEBI ID: CHEBI:65345
  CAS Number: 502632-66-8
  DrugBank ID: DB12601
  TTD ID: D0AW5T

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
PI3-kinase gamma (PIK3CG)	TTHBTOP	PK3CG_HUMAN	Inhibitor	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Bcl2-associated agonist of cell death (BAD)	OT63ERYM	BAD_HUMAN	Post-Translational Modifications	[3]
Calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2)	OT9C3KFI	KKCC2_HUMAN	Drug Response	[4]
Cell division control protein 6 homolog (CDC6)	OTX93FE7	CDC6_HUMAN	Gene/Protein Processing	[5]
E3 ubiquitin-protein ligase Mdm2 (MDM2)	OTOVXARF	MDM2_HUMAN	Post-Translational Modifications	[6]
G1/S-specific cyclin-E2 (CCNE2)	OTBBUKQQ	CCNE2_HUMAN	Gene/Protein Processing	[5]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Post-Translational Modifications	[4]

Molecular Expression Atlas of This Drug

• The Studied Disease: Solid tumour/cancer
• ICD Disease Classification: 2A00-2F9Z

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
PI3-kinase gamma (PIK3CG)	DTT	PIK3CG	1.98E-01	-0.05	-0.55

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: 7941).
• [2] Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov. 2009 Aug;8(8):627-44.
• [3] Combined action of the dinuclear platinum compound BBR3610 with the PI3-K inhibitor PX-866 in glioblastoma. Int J Cancer. 2011 Feb 15;128(4):787-96. doi: 10.1002/ijc.25394.
• [4] Akt activation by Ca(2+)/calmodulin-dependent protein kinase kinase 2 (CaMKK2) in ovarian cancer cells. J Biol Chem. 2017 Aug 25;292(34):14188-14204. doi: 10.1074/jbc.M117.778464. Epub 2017 Jun 20.
• [5] Combinatorial PX-866 and Raloxifene Decrease Rb Phosphorylation, Cyclin E2 Transcription, and Proliferation of MCF-7 Breast Cancer Cells. J Cell Biochem. 2016 Jul;117(7):1688-96. doi: 10.1002/jcb.25462. Epub 2015 Dec 28.
• [6] Down-regulation of hTERT and Cyclin D1 transcription via PI3K/Akt and TGF- pathways in MCF-7 Cancer cells with PX-866 and Raloxifene. Exp Cell Res. 2016 May 15;344(1):95-102. doi: 10.1016/j.yexcr.2016.03.022. Epub 2016 Mar 23.