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
CHEBI:65326
CAS Number
957054-30-7
DrugBank ID
DB11663
TTD ID
D08QGT
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

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
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Gene/Protein Processing [4]
Atos homolog protein A (ATOSA) OTWFM5G0 ATOSA_HUMAN Gene/Protein Processing [5]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Regulation of Drug Effects [6]
Bcl-2-like protein 11 (BCL2L11) OTNQQWFJ B2L11_HUMAN Gene/Protein Processing [7]
Bcl2-associated agonist of cell death (BAD) OT63ERYM BAD_HUMAN Post-Translational Modifications [8]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Gene/Protein Processing [9]
Carbonic anhydrase 9 (CA9) OTNA51XT CAH9_HUMAN Gene/Protein Processing [10]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Gene/Protein Processing [11]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Protein Interaction/Cellular Processes [12]
Cathepsin B (CTSB) OTP9G5QB CATB_HUMAN Gene/Protein Processing [13]
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 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.
5 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.
6 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.
7 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.
8 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.
9 A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development. Toxicol Sci. 2013 Nov;136(1):216-41.
10 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.
11 PI3K inhibition enhances doxorubicin-induced apoptosis in sarcoma cells. PLoS One. 2012;7(12):e52898. doi: 10.1371/journal.pone.0052898. Epub 2012 Dec 31.
12 The PI3K inhibitor GDC-0941 combines with existing clinical regimens for superior activity in multiple myeloma. Oncogene. 2014 Jan 16;33(3):316-25. doi: 10.1038/onc.2012.594. Epub 2013 Jan 14.
13 GDC-0941 enhances the lysosomal compartment via TFEB and primes glioblastoma cells to lysosomal membrane permeabilization and cell death. Cancer Lett. 2013 Feb 1;329(1):27-36. doi: 10.1016/j.canlet.2012.09.007. Epub 2012 Sep 18.