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

General Information of Drug (ID: DMWC34B)

• Drug Name: BAG956 Drug Info
• Synonyms: NVP-BAG956; 853910-02-8; BAG 956; NVP-BAG956(BAG 956); BAG-956; UNII-4UFC2K6E50; 4UFC2K6E50; 2-Methyl-2-(4-(2-methyl-8-((pyridin-3-yl)ethynyl)imidazo(4,5-C)quinolin-1-yl)phenyl)propionitrile; 2-methyl-2-(4-(2-methyl-8-(pyridin-3-ylethynyl)-1H-imidazo[4,5-c]quinolin-1-yl)phenyl)propanenitrile; BAG956; 2-Methyl-2-{4-[2-methyl-8-(pyridin-3-ylethynyl)-1H-imidazo[4,5-c]quinolin-1-yl]phenyl}propanenitrile; 2-Methyl-2-[4-[2-methyl-8-[(pyridin-3-yl)ethynyl]imidazo[4,5-c]quinolin-1-yl]phenyl]propionitrile; NVP-BAG-956

Indication

Disease Entry	ICD 11	Status	REF
Haematological malignancy	2B33.Y	Investigative	[1]

• Therapeutic Class: Anticancer Agents
• Cross-matching ID:
  PubChem CID: 24882589
  CAS Number: CAS 853910-02-8
  TTD Drug ID: DMWC34B

Molecule-Related Drug Atlas

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	[3]
IPI-145	DMWA24P	Follicular lymphoma	2A80	Approved	[4]
Buparlisib	DM1WEHC	Breast cancer	2C60-2C65	Phase 3	[5]
Enzastaurin	DM5H0R9	Diffuse large B-cell lymphoma	2A81	Phase 3	[6]
Rigosertib	DMOSTXF	Myelodysplastic syndrome	2A37	Phase 3	[7]
GDC-0032	DMT4QHD	Breast cancer	2C60-2C65	Phase 3	[6]
PQR309	DMMCYZ8	Squamous head and neck cell carcinom	2D60.0	Phase 2	[8]
SAR245409	DMQM7IL	Solid tumour/cancer	2A00-2F9Z	Phase 2	[9]
XL147	DMML7BE	Solid tumour/cancer	2A00-2F9Z	Phase 2	[9]
SF1126	DML10K3	Head and neck cancer	2D42	Phase 2	[10]

Drug(s) Affected By Small ribosomal subunit protein eS6 (RPS6)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[11]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[12]
Crizotinib	DM4F29C	Non-small-cell lung cancer	2C25.Y	Approved	[13]
Glucosamine	DM4ZLFD	Osteoarthritis	FA00-FA05	Approved	[14]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[15]
Aspirin	DM672AH	Acute coronary syndrome	BA41	Approved	[16]
Testosterone	DM7HUNW	Hot flushes	GA30	Approved	[17]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[18]
Capivasertib	DM9SKW8	Breast cancer	2C60-2C65	Approved	[19]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[20]

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	[1]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Small ribosomal subunit protein eS6 (RPS6)	OTT4D1LN	RS6_HUMAN	Post-Translational Modifications	[2]

References

• [1] The PI3K/Akt pathway as a target in the treatment of hematologic malignancies. Anticancer Agents Med Chem. 2009 Jun;9(5):550-9.
• [2] Harnessing the PI3K/Akt/mTOR pathway in T-cell acute lymphoblastic leukemia: eliminating activity by targeting at different levels. Oncotarget. 2012 Aug;3(8):811-23. doi: 10.18632/oncotarget.579.
• [3] 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.
• [4] 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.
• [5] Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov. 2009 Aug;8(8):627-44.
• [6] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [7] 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.
• [8] 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).
• [9] 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).
• [10] 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.
• [11] Cannabidiol Reduces Leukemic Cell Size - But Is It Important?. Front Pharmacol. 2017 Mar 24;8:144. doi: 10.3389/fphar.2017.00144. eCollection 2017.
• [12] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [13] Crizotinib-resistant mutants of EML4-ALK identified through an accelerated mutagenesis screen. Chem Biol Drug Des. 2011 Dec;78(6):999-1005. doi: 10.1111/j.1747-0285.2011.01239.x. Epub 2011 Oct 31.
• [14] D-glucosamine down-regulates HIF-1alpha through inhibition of protein translation in DU145 prostate cancer cells. Biochem Biophys Res Commun. 2009 Apr 24;382(1):96-101. doi: 10.1016/j.bbrc.2009.02.129. Epub 2009 Feb 28.
• [15] Proteomics-based identification of differentially abundant proteins from human keratinocytes exposed to arsenic trioxide. J Proteomics Bioinform. 2014 Jul;7(7):166-178.
• [16] Potential anti-aging agents suppress the level of constitutive mTOR- and DNA damage- signaling. Aging (Albany NY). 2012 Dec;4(12):952-65. doi: 10.18632/aging.100521.
• [17] Androgen receptor-mTOR crosstalk is regulated by testosterone availability: implication for prostate cancer cell survival. Anticancer Res. 2010 Oct;30(10):3895-901.
• [18] Imatinib disturbs lysosomal function and morphology and impairs the activity of mTORC1 in human hepatocyte cell lines. Food Chem Toxicol. 2022 Apr;162:112869. doi: 10.1016/j.fct.2022.112869. Epub 2022 Feb 16.
• [19] 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.
• [20] 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.