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

General Information of Drug (ID: DMO5760)

• Drug Name: SR13668 Drug Info

Indication

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Phase 1	[1]

• Cross-matching ID:
  PubChem CID: 9845566
  CAS Number: CAS 637774-61-9
  TTD Drug ID: DMO5760

Molecule-Related Drug Atlas

Drug(s) Targeting RAC-gamma serine/threonine-protein kinase (AKT3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Capivasertib	DM9SKW8	Breast cancer	2C60-2C65	Approved	[4]
ARQ 092	DM5WK0J	Proteus syndrome	LD2C	Phase 2	[5]
MK-2206	DMT1OZ6	Rectal adenocarcinoma	2B92	Phase 2	[6]
GSK2141795	DMSHE70	Colorectal cancer	2B91.Z	Phase 2	[7]
M2698	DM3PVBJ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[8]
LYS-6KAKT1	DMLXGAI	Solid tumour/cancer	2A00-2F9Z	Phase 1	[9]
LY2780301	DM93AJW	Solid tumour/cancer	2A00-2F9Z	Phase 1	[10]
XL418	DME0F5W	Solid tumour/cancer	2A00-2F9Z	Phase 1	[11]
TCN-P	DMV0AH8	Acute myeloid leukaemia	2A60	Phase 1	[12]
GSK690693	DMRBVHE	Haematological malignancy	2B33.Y	Phase 1	[13]

Drug(s) Affected By Cytochrome P450 1A2 (CYP1A2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Zolmitriptan	DM1IB4Q	Migraine	8A80	Approved	[14]
Rofecoxib	DM3P5DA	Osteoarthritis	FA00-FA05	Approved	[14]
Etoricoxib	DM6A4NW	Rheumatoid arthritis	FA20	Approved	[14]
Capsaicin	DMGMF6V	Back pain	ME84.Z	Approved	[15]
Hesperetin	DMKER83	High blood cholesterol level	5C80.00	Approved	[16]
Stiripentol	DMMSDOY	Dravet syndrome	8A61.11	Approved	[17]
Nifedipine	DMSVOZT	Angina pectoris	BA40	Approved	[18]
Zileuton	DMVRIC2	Allergic asthma	CA23.0	Approved	[19]
Nicotine	DMWX5CO	Lung cancer	2C25.0	Approved	[20]
Clonidine	DM6RZ9Q	Attention deficit hyperactivity disorder	6A05.Z	Approved	[21]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
RAC-gamma serine/threonine-protein kinase (AKT3)	TTAZ05C	AKT3_HUMAN	Modulator	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Cytochrome P450 1A2 (CYP1A2)	OTLLBX48	CP1A2_HUMAN	Gene/Protein Processing	[3]

References

• [1] ClinicalTrials.gov (NCT00896207) Studying Different Formulations of SR13668 in Healthy Volunteers. U.S. National Institutes of Health.
• [2] Phase 0 clinical chemoprevention trial of the Akt inhibitor SR13668. Cancer Prev Res (Phila). 2011 Mar;4(3):347-53.
• [3] In vitro assessment of P450 induction potential of novel chemopreventive agents SR13668, 9-cis-UAB30, and pentamethychromanol in primary cultures of human hepatocytes. Chem Biol Interact. 2009 May 15;179(2-3):263-72.
• [4] The novel AKT inhibitor afuresertib shows favorable safety, pharmacokinetics, and clinical activity in multiple myeloma. Blood. 2014 Oct 2;124(14):2190-5.
• [5] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [6] First-in-man clinical trial of the oral pan-AKT inhibitor MK-2206 in patients with advanced solid tumors.J Clin Oncol.2011 Dec 10;29(35):4688-95.
• [7] Inhibiting the akt pathway in cancer treatment: three leading candidates. P T. 2011 Apr;36(4):225-7.
• [8] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [9] DOI: 10.1016/S1359-6349(10)71767-5
• [10] A first-in-human phase I trial of LY2780301, a dual p70 S6 kinase and Akt Inhibitor, in patients with advanced or metastatic cancer. Invest New Drugs. 2015 Jun;33(3):710-9.
• [11] Targeting the phosphoinositide 3-kinase (PI3K) pathway in cancer
• [12] Phase I pharmacokinetic and pharmacodynamic study of triciribine phosphate monohydrate, a small-molecule inhibitor of AKT phosphorylation, in adult subjects with solid tumors containing activated AKT.Invest New Drugs.2011 Dec;29(6):1381-9.
• [13] Characterization of an Akt kinase inhibitor with potent pharmacodynamic and antitumor activity.Cancer Res.2008 Apr 1;68(7):2366-74.
• [14] In vitro inhibition of CYP1A2 by model inhibitors, anti-inflammatory analgesics and female sex steroids: predictability of in vivo interactions. Basic Clin Pharmacol Toxicol. 2008 Aug;103(2):157-65.
• [15] Effects of capsaicin and dihydrocapsaicin on human and rat liver microsomal CYP450 enzyme activities in vitro and in vivo. J Asian Nat Prod Res. 2012;14(4):382-95.
• [16] Drug interaction study of flavonoids toward CYP3A4 and their quantitative structure activity relationship (QSAR) analysis for predicting potential effects. Toxicol Lett. 2018 Sep 15;294:27-36.
• [17] Stiripentol. Expert Opin Investig Drugs. 2005 Jul;14(7):905-11.
• [18] Inhibition of human cytochrome P450 enzymes by 1,4-dihydropyridine calcium antagonists: prediction of in vivo drug-drug interactions. Eur J Clin Pharmacol. 2000 Feb-Mar;55(11-12):843-52.
• [19] Mechanism-based inhibition of human liver microsomal cytochrome P450 1A2 by zileuton, a 5-lipoxygenase inhibitor. Drug Metab Dispos. 2003 Nov;31(11):1352-60.
• [20] Predictive three-dimensional quantitative structure-activity relationship of cytochrome P450 1A2 inhibitors. J Med Chem. 2005 Jun 2;48(11):3808-15.
• [21] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.