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

General Information of Drug (ID: DML36ZE)

• Drug Name: LY-292223 Drug Info
• Synonyms: 2-(4-Morpholinyl)-4H-1-benzopyran-4-one; 2-morpholinochromone; LY-292223; CHEMBL367315; 2-morpholino-4H-chromen-4-one; 130735-56-7; U67154; AC1L2YUR; U-67154; SCHEMBL3361567; 2-morpholin-4-ylchromen-4-one; DTXSID30156701; 2-Morpholin-4-yl-chromen-4-one; QNFWERYZJLBANZ-UHFFFAOYSA-N; BDBM50098118; 2-(4-Morpholinyl)-4H-benzopyran-4-one; 4H-1-Benzopyran-4-one, 2-(4-morpholinyl)-

Indication

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

• Cross-matching ID:
  PubChem CID: 131255
  CAS Number: CAS 130735-56-7
  TTD Drug ID: DML36ZE

Molecule-Related Drug Atlas

Drug(s) Targeting Endothelin-converting enzyme 1 (ECE1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
SCH-54470	DMEWLZ7	N. A.	N. A.	Terminated	[4]
CGS 35066	DMCHT27	Discovery agent	N.A.	Investigative	[5]
PO3 2-Nle-Trp-O-3K	DMW1XY4	Discovery agent	N.A.	Investigative	[6]
PMID19899765C22	DMBTV20	Discovery agent	N.A.	Investigative	[4]
PO3 2-Leu-Trp-O-3K	DM3O78D	Discovery agent	N.A.	Investigative	[6]
5-(2-hydroxyethyl)nonane-1,9-diol	DMHBD1T	Discovery agent	N.A.	Investigative	[7]
PO3 2-Ile-Trp-O-3K	DMQMDSG	Discovery agent	N.A.	Investigative	[6]
PD159790	DM6RVTO	Discovery agent	N.A.	Investigative	[8]
PO3 2-Leu-Nal-O-3K	DMY43FU	Discovery agent	N.A.	Investigative	[6]

Drug(s) Targeting PI3-kinase delta (PIK3CD)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Bay 80-6946	DMLOS5R	Follicular lymphoma	2A80	Approved	[9]
Idelalisib	DM602WT	Chronic lymphocytic leukaemia	2A82.0	Approved	[10]
Umbralisib	DMYRBO1	Follicular lymphoma	2A80	Approved	[11]
IPI-145	DMWA24P	Follicular lymphoma	2A80	Approved	[12]
Buparlisib	DM1WEHC	Breast cancer	2C60-2C65	Phase 3	[13]
INCB50465	DMZJP2T	Diffuse large B-cell lymphoma	2A81	Phase 2	[14]
RP6530	DMYILGK	Chronic lymphocytic leukaemia	2A82.0	Phase 2	[14]
Leniolisib	DMWAD93	Sjogren syndrome	4A43.20	Phase 2	[15]
Parsaclisib	DMYBIFS	Follicular lymphoma	2A80	Phase 2	[16]
PA-799	DMLSYJQ	Colorectal cancer	2B91.Z	Phase 1/2	[17]

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	[14]
AZD7648	DMD9Y5T	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[18]
M9831	DM59TI2	Solid tumour/cancer	2A00-2F9Z	Phase 1	[14]
PP121	DMU8KTO	Discovery agent	N.A.	Investigative	[19]
Ethyl 1-[(1H-benzimidazol-2(3H)one-5-yl)sulfonyl]-1H-pyrrole-2-carboxylate	DM3FH02	Discovery agent	N.A.	Investigative	[20]
PIK-75	DM9BQTX	Discovery agent	N.A.	Investigative	[21]
KU-0060648	DMQWS6U	Discovery agent	N.A.	Investigative	[22]
Alpha-naphthoflavone	DMELOIQ	Discovery agent	N.A.	Investigative	[23]
2-Morpholin-4-yl-pyrimido[2,1-a]isoquinolin-4-one	DM79ZOV	Discovery agent	N.A.	Investigative	[23]
2-(2-Methyl-morpholin-4-yl)-benzo[h]chromen-4-one	DMAHZR9	Discovery agent	N.A.	Investigative	[3]

Drug(s) Targeting Angiotensin-converting enzyme (ACE)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Enalapril	DMNFUZR	Hypertension	BA00-BA04	Approved	[24]
Spirapril	DM5XLTY	Hypertension	BA00-BA04	Approved	[25]
Captopril	DM458UM	Hypertension	BA00-BA04	Approved	[26]
Benazepril	DMH1M9B	Hypertension	BA00-BA04	Approved	[27]
Moexipril	DM26E4B	Hypertension	BA00-BA04	Approved	[28]
Ramipril	DM2R68E	Congestive heart failure	BD10	Approved	[29]
Perindopril	DMOPZDT	Hypertension	BA00-BA04	Approved	[30]
Trandolapril	DM4L6EU	Hypertension	BA00-BA04	Approved	[31]
Fosinopril	DM9NJ52	Hypertension	BA00-BA04	Approved	[32]
Lisinopril	DMUOK4C	Hypertension	BA00-BA04	Approved	[33]

Drug(s) Targeting PI3K p110 beta messenger RNA (PIK3CB mRNA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ethyl 1-[(1H-benzimidazol-2(3H)one-5-yl)sulfonyl]-1H-pyrrole-2-carboxylate	DM3FH02	Discovery agent	N.A.	Investigative	[1]
3-(4-morpholinothieno[3,2-d]pyrimidin-2-yl)phenol	DM54MDH	Discovery agent	N.A.	Investigative	[34]
ISIS 32014	DMF5SK8	Discovery agent	N.A.	Investigative	[35]
ISIS 32024	DMPKGIU	Discovery agent	N.A.	Investigative	[35]
ISIS 32035	DM47B2O	Discovery agent	N.A.	Investigative	[35]
ISIS 32000	DM0O9WM	Discovery agent	N.A.	Investigative	[35]
ISIS 32021	DMISB5V	Discovery agent	N.A.	Investigative	[35]
ISIS 32003	DM7EVQX	Discovery agent	N.A.	Investigative	[35]
ISIS 32028	DMATWDO	Discovery agent	N.A.	Investigative	[35]
ISIS 32039	DMY1R0Q	Discovery agent	N.A.	Investigative	[35]

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	[36]
IPI-145	DMWA24P	Follicular lymphoma	2A80	Approved	[12]
Buparlisib	DM1WEHC	Breast cancer	2C60-2C65	Phase 3	[13]
Enzastaurin	DM5H0R9	Diffuse large B-cell lymphoma	2A81	Phase 3	[14]
Rigosertib	DMOSTXF	Myelodysplastic syndrome	2A37	Phase 3	[37]
GDC-0032	DMT4QHD	Breast cancer	2C60-2C65	Phase 3	[14]
PQR309	DMMCYZ8	Squamous head and neck cell carcinom	2D60.0	Phase 2	[38]
SAR245409	DMQM7IL	Solid tumour/cancer	2A00-2F9Z	Phase 2	[39]
Xl147	DMML7BE	Solid tumour/cancer	2A00-2F9Z	Phase 2	[39]
SF1126	DML10K3	Head and neck cancer	2D42	Phase 2	[40]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Angiotensin-converting enzyme (ACE)	TTL69WB	ACE_HUMAN	Inhibitor	[2]
DNA-dependent protein kinase catalytic (PRKDC)	TTK3PY9	PRKDC_HUMAN	Inhibitor	[3]
Endothelin-converting enzyme 1 (ECE1)	TTQ9RYT	ECE1_HUMAN	Inhibitor	[2]
PI3-kinase delta (PIK3CD)	TTGBPJE	PK3CD_HUMAN	Inhibitor	[1]
PI3-kinase gamma (PIK3CG)	TTHBTOP	PK3CG_HUMAN	Inhibitor	[1]
PI3K p110 beta messenger RNA (PIK3CB mRNA)	TT9H4P3	PK3CB_HUMAN	Inhibitor	[1]

References

• [1] LY294002-geldanamycin heterodimers as selective inhibitors of the PI3K and PI3K-related family. Bioorg Med Chem Lett. 2001 Apr 9;11(7):909-13.
• [2] Endothelin-converting enzyme-1 inhibition and growth of human glioblastoma cells. J Med Chem. 2005 Jan 27;48(2):483-98.
• [3] 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.
• [4] Phosphinic tripeptides as dual angiotensin-converting enzyme C-domain and endothelin-converting enzyme-1 inhibitors. J Med Chem. 2010 Jan 14;53(1):208-20.
• [5] The therapeutic potential of endothelin-1 receptor antagonists and endothelin-converting enzyme inhibitors on the cardiovascular system. Expert Opin Investig Drugs. 2002 Nov;11(11):1537-52.
• [6] Aminophosphonate endothelin converting enzyme inhibitors: potency-enhancing and selectivity-improving modifications of phosphoramidon, Bioorg. Med. Chem. Lett. 4(10):1257-1262 (1994).
• [7] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [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: 1615).
• [9] 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
• [10] 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
• [11] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2021
• [12] 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.
• [13] Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov. 2009 Aug;8(8):627-44.
• [14] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [15] Effective "activated PI3K syndrome"-targeted therapy with the PI3K inhibitor leniolisib. Blood. 2017 Nov 23;130(21):2307-2316.
• [16] Parsaclisib, a potent and highly selective PI3K inhibitor, in patients with relapsed or refractory B-cell malignancies. Blood. 2019 Apr 18;133(16):1742-1752.
• [17] The selective class I PI3K inhibitor CH5132799 targets human cancers harboring oncogenic PIK3CA mutations. Clin Cancer Res. 2011 May 15;17(10):3272-81.
• [18] AZD7648 is a potent and selective DNA-PK inhibitor that enhances radiation, chemotherapy and olaparib activity. Nat Commun. 2019 Nov 7;10(1):5065.
• [19] Targeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases. Nat Chem Biol. 2008 Nov;4(11):691-9.
• [20] 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.
• [21] A pharmacological map of the PI3-K family defines a role for p110alpha in insulin signaling. Cell. 2006 May 19;125(4):733-47.
• [22] 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.
• [23] 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.
• [24] Determination of bezafibrate, methotrexate, cyclophosphamide, orlistat and enalapril in waste and surface waters using on-line solid-phase extracti... J Environ Monit. 2009 Apr;11(4):830-8.
• [25] Central angiotensin II controls alcohol consumption via its AT1 receptor. FASEB J. 2005 Sep;19(11):1474-81.
• [26] Using ACE inhibitors appropriately. Am Fam Physician. 2002 Aug 1;66(3):461-8.
• [27] Efficacy of benazepril hydrochloride to delay the progression of occult dilated cardiomyopathy in Doberman Pinschers. J Vet Intern Med. 2009 Sep-Oct;23(5):977-83.
• [28] Moexipril for treatment of primary biliary cirrhosis in patients with an incomplete response to ursodeoxycholic acid. Dig Dis Sci. 2010 Feb;55(2):476-83.
• [29] Knockouts model the 100 best-selling drugs--will they model the next 100 Nat Rev Drug Discov. 2003 Jan;2(1):38-51.
• [30] Fixed combination perindopril-amlodipine (Coveram) in the treatment of hypertension and coronary heart disease. Rev Med Liege. 2009 Apr;64(4):223-7.
• [31] Selective reduction of central pulse pressure under angiotensin blockage in SHR: role of the fibronectin-alpha5beta1 integrin complex. Am J Hypertens. 2009 Jul;22(7):711-7.
• [32] Angiotensin-converting enzyme inhibition and novel cardiovascular risk biomarkers: results from the Trial of Angiotensin Converting Enzyme Inhibition and Novel Cardiovascular Risk Factors (TRAIN) study. Am Heart J. 2009 Feb;157(2):334.e1-8.
• [33] Involvement of vascular angiotensin II-forming enzymes in the progression of aortic abdominal aneurysms in angiotensin II- infused ApoE-deficient m... J Atheroscler Thromb. 2009 Jun;16(3):164-71.
• [34] 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.
• [35] US patent application no. 6,133,032, Antisense modulation of PI3 kinase p110 beta expression.
• [36] 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.
• [37] 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.
• [38] 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).
• [39] 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).
• [40] 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.