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: CHEMBL411907
CAS Number: CAS 502632-66-8
TTD Drug ID: DMYISJK

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	[6]
IPI-145	DMWA24P	Follicular lymphoma	2A80	Approved	[7]
Buparlisib	DM1WEHC	Breast cancer	2C60-2C65	Phase 3	[2]
Enzastaurin	DM5H0R9	Diffuse large B-cell lymphoma	2A81	Phase 3	[8]
Rigosertib	DMOSTXF	Myelodysplastic syndrome	2A37	Phase 3	[9]
GDC-0032	DMT4QHD	Breast cancer	2C60-2C65	Phase 3	[8]
PQR309	DMMCYZ8	Squamous head and neck cell carcinom	2D60.0	Phase 2	[10]
SAR245409	DMQM7IL	Solid tumour/cancer	2A00-2F9Z	Phase 2	[11]
XL147	DMML7BE	Solid tumour/cancer	2A00-2F9Z	Phase 2	[11]
SF1126	DML10K3	Head and neck cancer	2D42	Phase 2	[12]
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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	[13]
Aprepitant	DM053KT	Depression	6A70-6A7Z	Approved	[14]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[15]
Sulindac	DM2QHZU	Acute myelogenous leukaemia	2A41	Approved	[16]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[17]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[18]
obeticholic acid	DM3Q1SM	Primary biliary cholangitis	DB96.1	Approved	[19]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[20]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[21]
Aspirin	DM672AH	Acute coronary syndrome	BA41	Approved	[22]
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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	[23]
Colchicine	DM2POTE	Acute gout flare	FA25.0	Approved	[24]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[25]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[26]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[27]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[28]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[29]
Testosterone	DM7HUNW	Hot flushes	GA30	Approved	[30]
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[30]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[31]
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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	[32]
Clodronate	DM9Y6X7	Hypercalcaemia	5B91.0	Approved	[33]
Cidofovir	DMA13GD	Cytomegalovirus infection	1D82	Approved	[33]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[34]
Ifosfamide	DMCT3I8	Adult central nervous system germ cell tumor		Approved	[33]
Cupric Sulfate	DMP0NFQ	Fungal infection	1F29-1F2F	Approved	[35]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[36]
Arsenic	DMTL2Y1	N. A.	N. A.	Approved	[37]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[38]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[39]
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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]

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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]

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References

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2	Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov. 2009 Aug;8(8):627-44.
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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	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.
7	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.
8	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
9	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.
10	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).
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: 2156).
12	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.
13	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.
14	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.
15	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.
16	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.
17	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.
18	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.
19	Pharmacotoxicology of clinically-relevant concentrations of obeticholic acid in an organotypic human hepatocyte system. Toxicol In Vitro. 2017 Mar;39:93-103.
20	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.
21	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.
22	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.
23	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.
24	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.
25	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.
26	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.
27	Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
28	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.
29	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.
30	Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
31	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.
32	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.
33	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.
34	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.
35	Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
36	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.
37	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.
38	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.
39	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.