Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMYISJK)

Drug Name
PX-866 Drug Info
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]
Cross-matching ID
PubChem CID
9849735
ChEBI ID
CHEBI:65345
CAS Number
CAS 502632-66-8
TTD Drug ID
DMYISJK

Molecule-Related Drug Atlas

Molecule-Related Drug Atlas
Molecule Type:
DTT
DOT
Drug Status:
Approved Drug(s)
Clinical Trial Drug(s)
Download the Complete Related Drug List
Drug(s) Targeting PI3-kinase gamma (PIK3CG)
Drug Name Drug ID Indication ICD 11 Highest Status REF
BAY 80-6946 DMLOS5R Follicular lymphoma 2A80 Approved [7]
IPI-145 DMWA24P Follicular lymphoma 2A80 Approved [8]
Buparlisib DM1WEHC Breast cancer 2C60-2C65 Phase 3 [2]
Enzastaurin DM5H0R9 Diffuse large B-cell lymphoma 2A81 Phase 3 [9]
Rigosertib DMOSTXF Myelodysplastic syndrome 2A37 Phase 3 [10]
GDC-0032 DMT4QHD Breast cancer 2C60-2C65 Phase 3 [9]
PQR309 DMMCYZ8 Squamous head and neck cell carcinom 2D60.0 Phase 2 [11]
SAR245409 DMQM7IL Solid tumour/cancer 2A00-2F9Z Phase 2 [12]
XL147 DMML7BE Solid tumour/cancer 2A00-2F9Z Phase 2 [12]
SF1126 DML10K3 Head and neck cancer 2D42 Phase 2 [13]
⏷ Show the Full List of 10 Drug(s)
Drug(s) Affected By G1/S-specific cyclin-E2 (CCNE2)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Cannabidiol DM0659E Dravet syndrome 8A61.11 Approved [14]
Fulvestrant DM0YZC6 Breast cancer 2C60-2C65 Approved [15]
Colchicine DM2POTE Acute gout flare FA25.0 Approved [16]
Methotrexate DM2TEOL Anterior urethra cancer Approved [17]
Quercetin DM3NC4M Obesity 5B81 Approved [18]
Tretinoin DM49DUI Acne vulgaris ED80 Approved [19]
Zidovudine DM4KI7O Human immunodeficiency virus infection 1C62 Approved [20]
Hydroquinone DM6AVR4 Melasma ED60.1 Approved [21]
Testosterone DM7HUNW Hot flushes GA30 Approved [22]
Ibuprofen DM8VCBE Dysmenorrhea GA34.3 Approved [23]
⏷ Show the Full List of 10 Drug(s)
Drug(s) Affected By RAC-alpha serine/threonine-protein kinase (AKT1)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Capivasertib DM9SKW8 Breast cancer 2C60-2C65 Approved [24]
Nicotine DMWX5CO Lung cancer 2C25.0 Approved [25]
Cannabidiol DM0659E Dravet syndrome 8A61.11 Approved [26]
Beta-carotene DM0RXBT Vitamin deficiency 5B55-5B71 Approved [27]
Gefitinib DM15F0X Colon adenocarcinoma Approved [28]
Hydrogen peroxide DM1NG5W Infectious disease 1A00-CA43.1 Approved [29]
Imiquimod DM1TMA3 Alopecia areata ED70.2 Approved [30]
Selenium DM25CGV N. A. N. A. Approved [31]
Methimazole DM25FL8 Hyperthyroidism 5A02 Approved [32]
Ribavirin DMEYLH9 Hepatitis C virus infection 1E51.1 Approved [33]
⏷ Show the Full List of 10 Drug(s)
Drug(s) Affected By E3 ubiquitin-protein ligase Mdm2 (MDM2)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Cannabidiol DM0659E Dravet syndrome 8A61.11 Approved [34]
Flucytosine DM13VTW Cryptococcal meningitis Approved [35]
Ganciclovir DM1MBYQ Cytomegalovirus infection 1D82 Approved [35]
Hydrogen peroxide DM1NG5W Infectious disease 1A00-CA43.1 Approved [36]
Methotrexate DM2TEOL Anterior urethra cancer Approved [37]
Simvastatin DM30SGU Arteriosclerosis BD40 Approved [38]
Quercetin DM3NC4M Obesity 5B81 Approved [39]
Zidovudine DM4KI7O Human immunodeficiency virus infection 1C62 Approved [40]
Acetic Acid, Glacial DM4SJ5Y infection in the ear canal AA0Y Approved [41]
Amifostine DM5FL14 Mucositis CA00 Approved [42]
⏷ Show the Full List of 10 Drug(s)
Drug(s) Affected By Bcl2-associated agonist of cell death (BAD)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Paclitaxel DMLB81S Breast carcinoma Approved [43]
Aprepitant DM053KT Depression 6A70-6A7Z Approved [44]
Cannabidiol DM0659E Dravet syndrome 8A61.11 Approved [34]
Sulindac DM2QHZU Acute myelogenous leukaemia 2A41 Approved [45]
Simvastatin DM30SGU Arteriosclerosis BD40 Approved [46]
Quercetin DM3NC4M Obesity 5B81 Approved [47]
obeticholic acid DM3Q1SM Primary biliary cholangitis DB96.1 Approved [48]
Tretinoin DM49DUI Acne vulgaris ED80 Approved [49]
Arsenic trioxide DM61TA4 Acute lymphoblastic leukaemia 2A85 Approved [50]
Aspirin DM672AH Acute coronary syndrome BA41 Approved [51]
⏷ Show the Full List of 10 Drug(s)
Drug(s) Affected By Cell division control protein 6 homolog (CDC6)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Cannabidiol DM0659E Dravet syndrome 8A61.11 Approved [14]
Colchicine DM2POTE Acute gout flare FA25.0 Approved [16]
Simvastatin DM30SGU Arteriosclerosis BD40 Approved [52]
Quercetin DM3NC4M Obesity 5B81 Approved [53]
Troglitazone DM3VFPD Diabetic complication 5A2Y Approved [54]
Tretinoin DM49DUI Acne vulgaris ED80 Approved [55]
Arsenic trioxide DM61TA4 Acute lymphoblastic leukaemia 2A85 Approved [56]
Testosterone DM7HUNW Hot flushes GA30 Approved [22]
Calcitriol DM8ZVJ7 Congenital alopecia LC30 Approved [22]
Ciclosporin DMAZJFX Graft-versus-host disease 4B24 Approved [57]
⏷ Show the Full List of 10 Drug(s)
Drug(s) Affected By Calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Testosterone DM7HUNW Hot flushes GA30 Approved [58]
Clodronate DM9Y6X7 Hypercalcaemia 5B91.0 Approved [23]
Cidofovir DMA13GD Cytomegalovirus infection 1D82 Approved [23]
Valproate DMCFE9I Epilepsy 8A60-8A68 Approved [59]
Ifosfamide DMCT3I8 Adult central nervous system germ cell tumor Approved [23]
Cupric Sulfate DMP0NFQ Fungal infection 1F29-1F2F Approved [60]
Cisplatin DMRHGI9 Adenocarcinoma 2D40 Approved [61]
Arsenic DMTL2Y1 N. A. N. A. Approved [62]
Estradiol DMUNTE3 Acne vulgaris ED80 Approved [63]
Doxorubicin DMVP5YE Acute myelogenous leukaemia 2A41 Approved [64]
⏷ Show the Full List of 10 Drug(s)

Molecular Interaction Atlas of This Drug

Molecular Interaction Atlas
Download the Complete Interaction Atlas for Visualization in Cytoscape

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]

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.
7 BAY 80-6946 is a highly selective intravenous PI3K inhibitor with potent p110 and p110 activities in tumor cell lines and xenograft models.Mol Cancer Ther.2013 Nov;12(11):2319-30.
8 PI3K-delta and PI3K-gamma inhibition by IPI-145 abrogates immune responses and suppresses activity in autoimmune and inflammatory disease models. Chem Biol. 2013 Nov 21;20(11):1364-74.
9 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
10 Phase I study of oral rigosertib (ON 01910.Na), a dual inhibitor of the PI3K and Plk1 pathways, in adult patients with advanced solid malignancies. Clin Cancer Res. 2014 Mar 15;20(6):1656-65.
11 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. (Target id: 2155).
12 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. (Target id: 2156).
13 An integrin-targeted, pan-isoform, phosphoinositide-3 kinase inhibitor, SF1126, has activity against multiple myeloma in vivo.Cancer Chemother Pharmacol.2013 Apr;71(4):867-81.
14 Cannabidiol-induced transcriptomic changes and cellular senescence in human Sertoli cells. Toxicol Sci. 2023 Feb 17;191(2):227-238. doi: 10.1093/toxsci/kfac131.
15 mTOR inhibition reverses acquired endocrine therapy resistance of breast cancer cells at the cell proliferation and gene-expression levels. Cancer Sci. 2008 Oct;99(10):1992-2003. doi: 10.1111/j.1349-7006.2008.00955.x.
16 Utilization of CDKN1A/p21 gene for class discrimination of DNA damage-induced clastogenicity. Toxicology. 2014 Jan 6;315:8-16. doi: 10.1016/j.tox.2013.10.009. Epub 2013 Nov 6.
17 Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
18 Inhibition of prostate cancer cell colony formation by the flavonoid quercetin correlates with modulation of specific regulatory genes. Clin Diagn Lab Immunol. 2004 Jan;11(1):63-9. doi: 10.1128/cdli.11.1.63-69.2004.
19 Retinoic acid-induced downmodulation of telomerase activity in human cancer cells. Exp Mol Pathol. 2005 Oct;79(2):108-17.
20 Zidovudine induces S-phase arrest and cell cycle gene expression changes in human cells. Mutagenesis. 2005 Mar;20(2):139-46. doi: 10.1093/mutage/gei019. Epub 2005 Mar 22.
21 In vitro effects of aldehydes present in tobacco smoke on gene expression in human lung alveolar epithelial cells. Toxicol In Vitro. 2013 Apr;27(3):1072-81.
22 Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
23 Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
24 Inhibition of cholesterol metabolism underlies synergy between mTOR pathway inhibition and chloroquine in bladder cancer cells. Oncogene. 2016 Aug 25;35(34):4518-28. doi: 10.1038/onc.2015.511. Epub 2016 Feb 8.
25 Nicotine-induced survival signaling in lung cancer cells is dependent on their p53 status while its down-regulation by curcumin is independent. Mol Cancer. 2010 Aug 20;9:220.
26 Role of miRNA in the regulation of cannabidiol-mediated apoptosis in neuroblastoma cells. Oncotarget. 2019 Jan 1;10(1):45-59. doi: 10.18632/oncotarget.26534. eCollection 2019 Jan 1.
27 -Carotene Induces Apoptosis in Human Esophageal Squamous Cell Carcinoma Cell Lines via the Cav-1/AKT/NF-B Signaling Pathway. J Biochem Mol Toxicol. 2016 Mar;30(3):148-57. doi: 10.1002/jbt.21773. Epub 2016 Jan 6.
28 Dihydromyricetin suppresses tumor growth via downregulation of the EGFR/Akt/survivin signaling pathway. J Biochem Mol Toxicol. 2023 Jun;37(6):e23328. doi: 10.1002/jbt.23328. Epub 2023 Feb 19.
29 Oxidative stress induces parallel autophagy and mitochondria dysfunction in human glioma U251 cells. Toxicol Sci. 2009 Aug;110(2):376-88. doi: 10.1093/toxsci/kfp101. Epub 2009 May 18.
30 Effect of toll-like receptor 7 and 9 targeted therapy to prevent the development of hepatocellular carcinoma. Liver Int. 2015 Mar;35(3):1063-76. doi: 10.1111/liv.12626. Epub 2014 Jul 30.
31 Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
32 Low-expressional IGF1 mediated methimazole-induced liver developmental toxicity in fetal mice. Toxicology. 2018 Sep 1;408:70-79. doi: 10.1016/j.tox.2018.07.004. Epub 2018 Jul 7.
33 Ribavirin augments doxorubicin's efficacy in human hepatocellular carcinoma through inhibiting doxorubicin-induced eIF4E activation. J Biochem Mol Toxicol. 2018 Jan;32(1). doi: 10.1002/jbt.22007. Epub 2017 Nov 7.
34 Cannabidiol Modulates the Immunophenotype and Inhibits the Activation of the Inflammasome in Human Gingival Mesenchymal Stem Cells. Front Physiol. 2016 Nov 24;7:559. doi: 10.3389/fphys.2016.00559. eCollection 2016.
35 Mechanisms of thymidine kinase/ganciclovir and cytosine deaminase/ 5-fluorocytosine suicide gene therapy-induced cell death in glioma cells. Oncogene. 2005 Feb 10;24(7):1231-43. doi: 10.1038/sj.onc.1208290.
36 In vitro antioxidant and antigenotoxic potentials of 3,5-O-di-galloylquinic acid extracted from Myrtus communis leaves and modulation of cell gene expression by H2O2. J Appl Toxicol. 2012 May;32(5):333-41.
37 Functional gene expression profile underlying methotrexate-induced senescence in human colon cancer cells. Tumour Biol. 2011 Oct;32(5):965-76.
38 HMG-CoA reductase inhibitors, statins, induce phosphorylation of Mdm2 and attenuate the p53 response to DNA damage. FASEB J. 2005 Mar;19(3):476-8. doi: 10.1096/fj.04-2745fje. Epub 2004 Dec 29.
39 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
40 Azidothymidine and cisplatin increase p14ARF expression in OVCAR-3 ovarian cancer cell line. Toxicol Appl Pharmacol. 2006 Oct 1;216(1):89-97. doi: 10.1016/j.taap.2006.04.015. Epub 2006 May 19.
41 Motexafin gadolinium and zinc induce oxidative stress responses and apoptosis in B-cell lymphoma lines. Cancer Res. 2005 Dec 15;65(24):11676-88.
42 Amifostine impairs p53-mediated apoptosis of human myeloid leukemia cells. Mol Cancer Ther. 2003 Sep;2(9):893-900.
43 Susceptibility to drug-induced apoptosis correlates with differential modulation of Bad, Bcl-2 and Bcl-xL protein levels. Cell Death Differ. 2000 Jun;7(6):574-86. doi: 10.1038/sj.cdd.4400688.
44 Neurokinin-1 receptor (NK1R) inhibition sensitizes APL cells to anti-tumor effect of arsenic trioxide via restriction of NF-B axis: Shedding new light on resistance to Aprepitant. Int J Biochem Cell Biol. 2018 Oct;103:105-114. doi: 10.1016/j.biocel.2018.08.010. Epub 2018 Aug 23.
45 Sulindac sulfide inhibits epidermal growth factor-induced phosphorylation of extracellular-regulated kinase 1/2 and Bad in human colon cancer cells. Cancer Res. 2003 Feb 1;63(3):616-20.
46 Simvastatin induces activation of the serine-threonine protein kinase AKT and increases survival of isolated human pancreatic islets. Transplantation. 2002 Oct 27;74(8):1063-9. doi: 10.1097/00007890-200210270-00001.
47 Quercetin regulates insulin like growth factor signaling and induces intrinsic and extrinsic pathway mediated apoptosis in androgen independent prostate cancer cells (PC-3). Mol Cell Biochem. 2010 Nov;344(1-2):173-84. doi: 10.1007/s11010-010-0540-4. Epub 2010 Jul 25.
48 Pharmacotoxicology of clinically-relevant concentrations of obeticholic acid in an organotypic human hepatocyte system. Toxicol In Vitro. 2017 Mar;39:93-103.
49 Down regulation of N-acetylglucosaminyltransferase V facilitates all-transretinoic acid to induce apoptosis of human hepatocarcinoma cells. Mol Cell Biochem. 2006 Mar;284(1-2):103-10. doi: 10.1007/s11010-005-9022-5. Epub 2006 Jan 13.
50 Arsenic trioxide induces different gene expression profiles of genes related to growth and apoptosis in glioma cells dependent on the p53 status. Mol Biol Rep. 2008 Sep;35(3):421-9.
51 Lunasin, a novel seed peptide, sensitizes human breast cancer MDA-MB-231 cells to aspirin-arrested cell cycle and induced apoptosis. Chem Biol Interact. 2010 Jul 30;186(2):127-34. doi: 10.1016/j.cbi.2010.04.027. Epub 2010 May 21.
52 Simvastatin inactivates beta1-integrin and extracellular signal-related kinase signaling and inhibits cell proliferation in head and neck squamous cell carcinoma cells. Cancer Sci. 2007 Jun;98(6):890-9.
53 Integrated assessment by multiple gene expression analysis of quercetin bioactivity on anticancer-related mechanisms in colon cancer cells in vitro. Eur J Nutr. 2005 Mar;44(3):143-56. doi: 10.1007/s00394-004-0503-1. Epub 2004 Apr 30.
54 Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
55 Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
56 Activation of the p38 MAPK/Akt/ERK1/2 signal pathways is required for the protein stabilization of CDC6 and cyclin D1 in low-dose arsenite-induced cell proliferation. J Cell Biochem. 2010 Dec 15;111(6):1546-55. doi: 10.1002/jcb.22886.
57 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
58 The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
59 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
60 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
61 Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
62 Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
63 Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
64 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.