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

General Information of Drug (ID: DMAHZR9)

• Drug Name: 2-(2-Methyl-morpholin-4-yl)-benzo[h]chromen-4-one Drug Info
• Synonyms: CHEMBL435507; 2-(2-Methyl-morpholin-4-yl)-benzo[h]chromen-4-one; SCHEMBL3545107

Indication

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

• Cross-matching ID:
  PubChem CID: 10017389
  TTD Drug ID: DMAHZR9

Molecule-Related Drug Atlas

Drug(s) Targeting Serine/threonine-protein kinase mTOR (mTOR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sirolimus	DMGW1ID	Advanced cancer	2A00-2F9Z	Approved	[3]
Temsirolimus	DMS104F	Renal cell carcinoma	2C90	Approved	[4]
PF-04449913	DMSB068	Chronic myelomonocytic leukaemia	2A40	Approved	[5]
Everolimus	DM8X2EH	Advanced cancer	2A00-2F9Z	Approved	[6]
Novolimus	DM6ZPLQ	Artery stenosis	BD52	Approved	[7]
Zotarolimus	DMRMCXW	Solid tumour/cancer	2A00-2F9Z	Approved	[8]
Ridaforolimus	DMLHEU7	Sarcoma	2A60-2C35	Phase 3	[9]
AZD2014	DMOEARH	Solid tumour/cancer	2A00-2F9Z	Phase 2	[10]
MM-141	DM2RJ4D	Pancreatic cancer	2C10	Phase 2	[11]
PQR309	DMMCYZ8	Squamous head and neck cell carcinom	2D60.0	Phase 2	[7]

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	[11]
AZD7648	DMD9Y5T	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[12]
M9831	DM59TI2	Solid tumour/cancer	2A00-2F9Z	Phase 1	[11]
PP121	DMU8KTO	Discovery agent	N.A.	Investigative	[13]
LY-292223	DML36ZE	Discovery agent	N.A.	Investigative	[1]
Ethyl 1-[(1H-benzimidazol-2(3H)one-5-yl)sulfonyl]-1H-pyrrole-2-carboxylate	DM3FH02	Discovery agent	N.A.	Investigative	[14]
PIK-75	DM9BQTX	Discovery agent	N.A.	Investigative	[15]
KU-0060648	DMQWS6U	Discovery agent	N.A.	Investigative	[16]
ALPHA-NAPHTHOFLAVONE	DMELOIQ	Discovery agent	N.A.	Investigative	[2]
2-Morpholin-4-yl-pyrimido[2,1-a]isoquinolin-4-one	DM79ZOV	Discovery agent	N.A.	Investigative	[2]

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	[1]
Serine/threonine-protein kinase mTOR (mTOR)	TTCJG29	MTOR_HUMAN	Inhibitor	[2]

References

• [1] 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.
• [2] 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.
• [3] Knockouts model the 100 best-selling drugs--will they model the next 100 Nat Rev Drug Discov. 2003 Jan;2(1):38-51.
• [4] Advances in kinase targeting: current clinical use and clinical trials. Trends Pharmacol Sci. 2014 Nov;35(11):604-20.
• [5] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [6] Mammalian target of rapamycin, its mode of action and clinical response in metastatic clear cell carcinoma. Gan To Kagaku Ryoho. 2009 Jul;36(7):1076-9.
• [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. (Target id: 2109).
• [8] Natural products to drugs: natural product-derived compounds in clinical trials. Nat Prod Rep. 2008 Jun;25(3):475-516.
• [9] A novel c-Met inhibitor, MK8033, synergizes with carboplatin plus paclitaxel to inhibit ovarian cancer cell growth. Oncol Rep. 2013 May;29(5):2011-8.
• [10] Dramatic suppression of colorectal cancer cell growth by the dual mTORC1 and mTORC2 inhibitor AZD-2014. Biochem Biophys Res Commun. 2014 Jan 10;443(2):406-12.
• [11] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [12] AZD7648 is a potent and selective DNA-PK inhibitor that enhances radiation, chemotherapy and olaparib activity. Nat Commun. 2019 Nov 7;10(1):5065.
• [13] Targeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases. Nat Chem Biol. 2008 Nov;4(11):691-9.
• [14] 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.
• [15] A pharmacological map of the PI3-K family defines a role for p110alpha in insulin signaling. Cell. 2006 May 19;125(4):733-47.
• [16] 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.