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

General Information of Drug (ID: DM9BQTX)

• Drug Name: PIK-75 Drug Info
• Synonyms: PIK75; PIK 75; imidazopyridine derivative 8c [PMID 17601739]

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 10275789
  ChEBI ID: CHEBI:94827
  CAS Number: CAS 945619-31-8
  TTD Drug ID: DM9BQTX

Molecule-Related Drug Atlas

Drug(s) Targeting PI3-kinase beta (PIK3CB)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Buparlisib	DM1WEHC	Breast cancer	2C60-2C65	Phase 3	[5]
PQR309	DMMCYZ8	Squamous head and neck cell carcinom	2D60.0	Phase 2	[6]
PA-799	DMLSYJQ	Colorectal cancer	2B91.Z	Phase 1/2	[7]
AZD8186	DMWYF1H	Solid tumour/cancer	2A00-2F9Z	Phase 1	[8]
GSK2636771	DMCBGLW	Prostate cancer	2C82.0	Phase 1	[9]
BAY 1082439	DMLRGX1	Solid tumour/cancer	2A00-2F9Z	Phase 1	[10]
AZD6482	DMVP4E5	Thrombosis	DB61-GB90	Terminated	[11]
PP121	DMU8KTO	Discovery agent	N.A.	Investigative	[12]
KU-0060648	DMQWS6U	Discovery agent	N.A.	Investigative	[13]
PI-3065	DMCQUWI	Discovery agent	N.A.	Investigative	[14]

Drug(s) Targeting DNA-dependent protein kinase catalytic (PRKDC)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
M3814	DMK2L38	Locally advanced rectal cancer	2B92	Phase 1/2	[15]
AZD7648	DMD9Y5T	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[16]
M9831	DM59TI2	Solid tumour/cancer	2A00-2F9Z	Phase 1	[15]
PP121	DMU8KTO	Discovery agent	N.A.	Investigative	[12]
LY-292223	DML36ZE	Discovery agent	N.A.	Investigative	[17]
Ethyl 1-[(1H-benzimidazol-2(3H)one-5-yl)sulfonyl]-1H-pyrrole-2-carboxylate	DM3FH02	Discovery agent	N.A.	Investigative	[18]
KU-0060648	DMQWS6U	Discovery agent	N.A.	Investigative	[13]
ALPHA-NAPHTHOFLAVONE	DMELOIQ	Discovery agent	N.A.	Investigative	[19]
2-Morpholin-4-yl-pyrimido[2,1-a]isoquinolin-4-one	DM79ZOV	Discovery agent	N.A.	Investigative	[19]
2-(2-Methyl-morpholin-4-yl)-benzo[h]chromen-4-one	DMAHZR9	Discovery agent	N.A.	Investigative	[17]

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	[20]
IPI-145	DMWA24P	Follicular lymphoma	2A80	Approved	[21]
Buparlisib	DM1WEHC	Breast cancer	2C60-2C65	Phase 3	[5]
Enzastaurin	DM5H0R9	Diffuse large B-cell lymphoma	2A81	Phase 3	[15]
Rigosertib	DMOSTXF	Myelodysplastic syndrome	2A37	Phase 3	[22]
GDC-0032	DMT4QHD	Breast cancer	2C60-2C65	Phase 3	[15]
PQR309	DMMCYZ8	Squamous head and neck cell carcinom	2D60.0	Phase 2	[23]
SAR245409	DMQM7IL	Solid tumour/cancer	2A00-2F9Z	Phase 2	[24]
XL147	DMML7BE	Solid tumour/cancer	2A00-2F9Z	Phase 2	[24]
SF1126	DML10K3	Head and neck cancer	2D42	Phase 2	[25]

Drug(s) Affected By Forkhead box protein O3 (FOXO3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[4]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[26]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[27]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[28]
Remdesivir	DMBFZ6L	Coronavirus Disease 2019 (COVID-19)	1D6Y	Approved	[29]
Acetic Acid, Glacial	DM4SJ5Y	infection in the ear canal	AA0Y	Approved	[30]
Nefazodone	DM4ZS8M	Major depressive disorder	6A70.3	Approved	[31]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[32]
Leflunomide	DMR8ONJ	Arthritis	FA20	Approved	[33]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[34]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
DNA-dependent protein kinase catalytic (PRKDC)	TTK3PY9	PRKDC_HUMAN	Inhibitor	[2]
PI3-kinase beta (PIK3CB)	TTTHBCA	PK3CB_HUMAN	Inhibitor	[3]
PI3-kinase gamma (PIK3CG)	TTHBTOP	PK3CG_HUMAN	Inhibitor	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Forkhead box protein O3 (FOXO3)	OTHXQG4P	FOXO3_HUMAN	Protein Interaction/Cellular Processes	[4]

References

• [1] Isoform-selective inhibition of phosphoinositide 3-kinase: identification of a new region of nonconserved amino acids critical for p110alpha inhibition. Mol Pharmacol. 2011 Oct;80(4):657-64.
• [2] A pharmacological map of the PI3-K family defines a role for p110alpha in insulin signaling. Cell. 2006 May 19;125(4):733-47.
• [3] Synthesis and biological evaluation of sulfonylhydrazone-substituted imidazo[1,2-a]pyridines as novel PI3 kinase p110alpha inhibitors. Bioorg Med Chem. 2007 Sep 1;15(17):5837-44.
• [4] Estrogen-mediated inactivation of FOXO3a by the G protein-coupled estrogen receptor GPER. BMC Cancer. 2015 Oct 15;15:702. doi: 10.1186/s12885-015-1699-6.
• [5] Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov. 2009 Aug;8(8):627-44.
• [6] 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: 2154).
• [7] The selective class I PI3K inhibitor CH5132799 targets human cancers harboring oncogenic PIK3CA mutations. Clin Cancer Res. 2011 May 15;17(10):3272-81.
• [8] National Cancer Institute Drug Dictionary (drug id 751594).
• [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. (Ligand id: 7967).
• [10] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [11] Human target validation of phosphoinositide 3-kinase (PI3K)beta: effects on platelets and insulin sensitivity, using AZD6482 a novel PI3Kbeta inhibitor. J Thromb Haemost. 2012 Oct;10(10):2127-36.
• [12] Targeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases. Nat Chem Biol. 2008 Nov;4(11):691-9.
• [13] 1-substituted (Dibenzo[b,d]thiophen-4-yl)-2-morpholino-4H-chromen-4-ones endowed with dual DNA-PK/PI3-K inhibitory activity. J Med Chem. 2013 Aug 22;56(16):6386-401.
• [14] Inactivation of PI(3)K p110delta breaks regulatory T-cell-mediated immune tolerance to cancer. Nature. 2014 Jun 19;510(7505):407-11.
• [15] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [16] AZD7648 is a potent and selective DNA-PK inhibitor that enhances radiation, chemotherapy and olaparib activity. Nat Commun. 2019 Nov 7;10(1):5065.
• [17] Identification of a highly potent and selective DNA-dependent protein kinase (DNA-PK) inhibitor (NU7441) by screening of chromenone libraries. Bioorg Med Chem Lett. 2004 Dec 20;14(24):6083-7.
• [18] Discovery of potent chromen-4-one inhibitors of the DNA-dependent protein kinase (DNA-PK) using a small-molecule library approach. J Med Chem. 2005 Dec 1;48(24):7829-46.
• [19] Selective benzopyranone and pyrimido[2,1-a]isoquinolin-4-one inhibitors of DNA-dependent protein kinase: synthesis, structure-activity studies, and... J Med Chem. 2005 Jan 27;48(2):569-85.
• [20] 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.
• [21] 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.
• [22] 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.
• [23] 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).
• [24] 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).
• [25] 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.
• [26] Differential expression of FOXO1 and FOXO3a confers resistance to oxidative cell death upon endometrial decidualization. Mol Endocrinol. 2006 Oct;20(10):2444-55. doi: 10.1210/me.2006-0118. Epub 2006 May 18.
• [27] Quercetin and Its Fermented Extract as a Potential Inhibitor of Bisphenol A-Exposed HT-29 Colon Cancer Cells' Viability. Int J Mol Sci. 2023 Mar 15;24(6):5604. doi: 10.3390/ijms24065604.
• [28] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [29] An in vitro study on anti-carcinogenic effect of remdesivir in human ovarian cancer cells via generation of reactive oxygen species. Hum Exp Toxicol. 2022 Jan-Dec;41:9603271221089257. doi: 10.1177/09603271221089257.
• [30] Motexafin gadolinium and zinc induce oxidative stress responses and apoptosis in B-cell lymphoma lines. Cancer Res. 2005 Dec 15;65(24):11676-88.
• [31] Involvement of mitochondrial dysfunction in nefazodone-induced hepatotoxicity. Food Chem Toxicol. 2016 Aug;94:148-58. doi: 10.1016/j.fct.2016.06.001. Epub 2016 Jun 8.
• [32] Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells. Toxicol Appl Pharmacol. 2012 Jun 1;261(2):204-16.
• [33] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [34] 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.