Details of the Drug

General Information of Drug (ID: DM1YAK6)

Drug Name
GDC0941
Synonyms
Pictilisib; GDC-0941; 957054-30-7; PICTILISIB; Pictrelisib; GDC 0941; 4-(2-(1H-Indazol-4-yl)-6-((4-(methylsulfonyl)piperazin-1-yl)methyl)thieno[3,2-d]pyrimidin-4-yl)morpholine; 2-(1H-Indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidine; UNII-ICY00EMP8P; ICY00EMP8P; Pictilisib (GDC-0941); CHEBI:65326; AK-40872; Thieno[3,2-d]pyrimidine, 2-(1H-indazol-4-yl)-6-[[4-(methylsulfonyl)-1-piperazinyl]methyl]-4-(4-morpholinyl)-; GD9; GDC-0941, GDC0941; 2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine
Indication
Disease Entry ICD 11 Status REF
Breast cancer 2C60-2C65 Phase 2 [1]
Non-hodgkin lymphoma 2B33.5 Phase 2 [2]
Solid tumour/cancer 2A00-2F9Z Phase 2 [2]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 1 Molecular Weight (mw) 513.6
Logarithm of the Partition Coefficient (xlogp) 1.6
Rotatable Bond Count (rotbonds) 5
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 10
Chemical Identifiers
Formula
C23H27N7O3S2
IUPAC Name
4-[2-(1H-indazol-4-yl)-6-[(4-methylsulfonylpiperazin-1-yl)methyl]thieno[3,2-d]pyrimidin-4-yl]morpholine
Canonical SMILES
CS(=O)(=O)N1CCN(CC1)CC2=CC3=C(S2)C(=NC(=N3)C4=C5C=NNC5=CC=C4)N6CCOCC6
InChI
InChI=1S/C23H27N7O3S2/c1-35(31,32)30-7-5-28(6-8-30)15-16-13-20-21(34-16)23(29-9-11-33-12-10-29)26-22(25-20)17-3-2-4-19-18(17)14-24-27-19/h2-4,13-14H,5-12,15H2,1H3,(H,24,27)
InChIKey
LHNIIDJUOCFXAP-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
17755052
ChEBI ID
CHEMBL521851
CAS Number
957054-30-7
UNII
ICY00EMP8P
DrugBank ID
DB11663
TTD ID
D08QGT
Drug-Molecule Activity Atlas (DMA)NEW Click to Jump to the Detailed DMA Information of This Drug
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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 [3]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Atos homolog protein A (ATOSA) OTWFM5G0 ATOSA_HUMAN Gene/Protein Processing [4]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Regulation of Drug Effects [5]
Bcl-2-like protein 11 (BCL2L11) OTNQQWFJ B2L11_HUMAN Gene/Protein Processing [6]
Bcl2-associated agonist of cell death (BAD) OT63ERYM BAD_HUMAN Post-Translational Modifications [7]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Gene/Protein Processing [8]
Carbonic anhydrase 9 (CA9) OTNA51XT CAH9_HUMAN Gene/Protein Processing [9]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Gene/Protein Processing [10]
Cyclin-dependent kinase inhibitor 1B (CDKN1B) OTNY5LLZ CDN1B_HUMAN Gene/Protein Processing [10]
Cyclin-G2 (CCNG2) OTII38K2 CCNG2_HUMAN Gene/Protein Processing [4]
Dendrin (DDN) OTM52ZF5 DEND_HUMAN Drug Response [11]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Breast cancer
ICD Disease Classification 2C60-2C65
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
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 Phase II Randomized Preoperative Window-of-Opportunity Study of the PI3K Inhibitor Pictilisib Plus Anastrozole Compared With Anastrozole Alone in P... J Clin Oncol. 2016 Jun 10;34(17):1987-94.
2 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: 5682).
3 Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov. 2009 Aug;8(8):627-44.
4 Phosphoinositide 3-kinase (PI3K) pathway alterations are associated with histologic subtypes and are predictive of sensitivity to PI3K inhibitors in lung cancer preclinical models. Clin Cancer Res. 2012 Dec 15;18(24):6771-83. doi: 10.1158/1078-0432.CCR-12-2347. Epub 2012 Nov 7.
5 Role of P-glycoprotein and breast cancer resistance protein-1 in the brain penetration and brain pharmacodynamic activity of the novel phosphatidylinositol 3-kinase inhibitor GDC-0941. Drug Metab Dispos. 2010 Sep;38(9):1422-6. doi: 10.1124/dmd.110.034256. Epub 2010 Jun 3.
6 Intermittent administration of MEK inhibitor GDC-0973 plus PI3K inhibitor GDC-0941 triggers robust apoptosis and tumor growth inhibition. Cancer Res. 2012 Jan 1;72(1):210-9. doi: 10.1158/0008-5472.CAN-11-1515. Epub 2011 Nov 14.
7 Pim 1 kinase inhibitor ETP-45299 suppresses cellular proliferation and synergizes with PI3K inhibition. Cancer Lett. 2011 Jan 28;300(2):145-53. doi: 10.1016/j.canlet.2010.09.016. Epub 2010 Nov 3.
8 A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development. Toxicol Sci. 2013 Nov;136(1):216-41.
9 GDC-0941 inhibits metastatic characteristics of thyroid carcinomas by targeting both the phosphoinositide-3 kinase (PI3K) and hypoxia-inducible factor-1 (HIF-1) pathways. J Clin Endocrinol Metab. 2011 Dec;96(12):E1934-43. doi: 10.1210/jc.2011-1426. Epub 2011 Oct 12.
10 The novel dual PI3K/mTOR inhibitor GDC-0941 synergizes with the MEK inhibitor U0126 in non-small cell lung cancer cells. Mol Med Rep. 2012 Feb;5(2):503-8. doi: 10.3892/mmr.2011.682. Epub 2011 Nov 16.
11 Modulators of sensitivity and resistance to inhibition of PI3K identified in a pharmacogenomic screen of the NCI-60 human tumor cell line collection. PLoS One. 2012;7(9):e46518. doi: 10.1371/journal.pone.0046518. Epub 2012 Sep 28.