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

General Information of Drug (ID: DMQWS6U)

• Drug Name: KU-0060648 Drug Info
• Synonyms: KU 0060648

Indication

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

• Cross-matching ID:
  PubChem CID: 11964036
  ChEBI ID: CHEBI:94302
  TTD Drug ID: DMQWS6U

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	[3]
PQR309	DMMCYZ8	Squamous head and neck cell carcinom	2D60.0	Phase 2	[4]
PA-799	DMLSYJQ	Colorectal cancer	2B91.Z	Phase 1/2	[5]
AZD8186	DMWYF1H	Solid tumour/cancer	2A00-2F9Z	Phase 1	[6]
GSK2636771	DMCBGLW	Prostate cancer	2C82.0	Phase 1	[7]
BAY 1082439	DMLRGX1	Solid tumour/cancer	2A00-2F9Z	Phase 1	[8]
AZD6482	DMVP4E5	Thrombosis	DB61-GB90	Terminated	[9]
PP121	DMU8KTO	Discovery agent	N.A.	Investigative	[10]
PIK-75	DM9BQTX	Discovery agent	N.A.	Investigative	[11]
PI-3065	DMCQUWI	Discovery agent	N.A.	Investigative	[12]

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	[13]
AZD7648	DMD9Y5T	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[14]
M9831	DM59TI2	Solid tumour/cancer	2A00-2F9Z	Phase 1	[13]
PP121	DMU8KTO	Discovery agent	N.A.	Investigative	[10]
LY-292223	DML36ZE	Discovery agent	N.A.	Investigative	[15]
Ethyl 1-[(1H-benzimidazol-2(3H)one-5-yl)sulfonyl]-1H-pyrrole-2-carboxylate	DM3FH02	Discovery agent	N.A.	Investigative	[16]
PIK-75	DM9BQTX	Discovery agent	N.A.	Investigative	[17]
ALPHA-NAPHTHOFLAVONE	DMELOIQ	Discovery agent	N.A.	Investigative	[18]
2-Morpholin-4-yl-pyrimido[2,1-a]isoquinolin-4-one	DM79ZOV	Discovery agent	N.A.	Investigative	[18]
2-(2-Methyl-morpholin-4-yl)-benzo[h]chromen-4-one	DMAHZR9	Discovery agent	N.A.	Investigative	[15]

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	[19]
IPI-145	DMWA24P	Follicular lymphoma	2A80	Approved	[20]
Buparlisib	DM1WEHC	Breast cancer	2C60-2C65	Phase 3	[3]
Enzastaurin	DM5H0R9	Diffuse large B-cell lymphoma	2A81	Phase 3	[13]
Rigosertib	DMOSTXF	Myelodysplastic syndrome	2A37	Phase 3	[21]
GDC-0032	DMT4QHD	Breast cancer	2C60-2C65	Phase 3	[13]
PQR309	DMMCYZ8	Squamous head and neck cell carcinom	2D60.0	Phase 2	[22]
SAR245409	DMQM7IL	Solid tumour/cancer	2A00-2F9Z	Phase 2	[23]
XL147	DMML7BE	Solid tumour/cancer	2A00-2F9Z	Phase 2	[23]
SF1126	DML10K3	Head and neck cancer	2D42	Phase 2	[24]

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	[2]
PI3-kinase gamma (PIK3CG)	TTHBTOP	PK3CG_HUMAN	Inhibitor	[2]

References

• [1] Chemosensitization of cancer cells by KU-0060648, a dual inhibitor of DNA-PK and PI-3K. Mol Cancer Ther. 2012 Aug;11(8):1789-98.
• [2] 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.
• [3] Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov. 2009 Aug;8(8):627-44.
• [4] 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).
• [5] The selective class I PI3K inhibitor CH5132799 targets human cancers harboring oncogenic PIK3CA mutations. Clin Cancer Res. 2011 May 15;17(10):3272-81.
• [6] National Cancer Institute Drug Dictionary (drug id 751594).
• [7] 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).
• [8] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [9] 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.
• [10] Targeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases. Nat Chem Biol. 2008 Nov;4(11):691-9.
• [11] 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.
• [12] Inactivation of PI(3)K p110delta breaks regulatory T-cell-mediated immune tolerance to cancer. Nature. 2014 Jun 19;510(7505):407-11.
• [13] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [14] AZD7648 is a potent and selective DNA-PK inhibitor that enhances radiation, chemotherapy and olaparib activity. Nat Commun. 2019 Nov 7;10(1):5065.
• [15] 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.
• [16] 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.
• [17] A pharmacological map of the PI3-K family defines a role for p110alpha in insulin signaling. Cell. 2006 May 19;125(4):733-47.
• [18] 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.
• [19] 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.
• [20] 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.
• [21] 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.
• [22] 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).
• [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: 2156).
• [24] 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.