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

General Information of Drug (ID: DMDVIT1)

• Drug Name: Akt inhibitor VIII Drug Info
• Synonyms: isozyme-selective, Akti-1/2

Indication

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

• Cross-matching ID:
  PubChem CID: 135398501
  ChEBI ID: CHEBI:91346
  CAS Number: CAS 612847-09-3
  TTD Drug ID: DMDVIT1

Molecule-Related Drug Atlas

Drug(s) Targeting RAC-alpha serine/threonine-protein kinase (AKT1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Capivasertib	DM9SKW8	Breast cancer	2C60-2C65	Approved	[2]
Enzastaurin	DM5H0R9	Diffuse large B-cell lymphoma	2A81	Phase 3	[2]
GDC-0068	DMWBZJD	Breast cancer	2C60-2C65	Phase 3	[2]
CI-1033	DMSI8N3	Lymphoma	2A80-2A86	Phase 2	[3]
CMX-2043	DMPSCVY	Cardiac disease	BA00-BE2Z	Phase 2	[4]
ARQ 092	DM5WK0J	Proteus syndrome	LD2C	Phase 2	[5]
GSK2110183	DMZHB37	leukaemia	2A60-2B33	Phase 2	[6]
RX-0201	DMTBAV3	Pancreatic cancer	2C10	Phase 2	[7]
PTX-200	DM0ZIT2	Breast cancer	2C60-2C65	Phase 2	[2]
Triciribine prodrug	DMBN1XS	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[6]

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	[8]
ARQ 092	DM5WK0J	Proteus syndrome	LD2C	Phase 2	[9]
MK-2206	DMT1OZ6	Rectal adenocarcinoma	2B92	Phase 2	[10]
GSK2141795	DMSHE70	Colorectal cancer	2B91.Z	Phase 2	[11]
M2698	DM3PVBJ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[2]
LYS-6KAKT1	DMLXGAI	Solid tumour/cancer	2A00-2F9Z	Phase 1	[12]
LY2780301	DM93AJW	Solid tumour/cancer	2A00-2F9Z	Phase 1	[13]
XL418	DME0F5W	Solid tumour/cancer	2A00-2F9Z	Phase 1	[14]
SR13668	DMO5760	Solid tumour/cancer	2A00-2F9Z	Phase 1	[15]
TCN-P	DMV0AH8	Acute myeloid leukaemia	2A60	Phase 1	[16]

Drug(s) Targeting RAC-beta serine/threonine-protein kinase (AKT2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PMID20005102C1	DMMESBW	Discovery agent	N.A.	Investigative	[17]
PHT-427	DMI96Y3	Discovery agent	N.A.	Investigative	[18]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
RAC-alpha serine/threonine-protein kinase (AKT1)	TTWTSCV	AKT1_HUMAN	Inhibitor	[1]
RAC-beta serine/threonine-protein kinase (AKT2)	TTH24WI	AKT2_HUMAN	Inhibitor	[1]
RAC-gamma serine/threonine-protein kinase (AKT3)	TTAZ05C	AKT3_HUMAN	Inhibitor	[1]

References

• [1] Allosteric Akt (PKB) inhibitors: discovery and SAR of isozyme selective inhibitors. Bioorg Med Chem Lett. 2005 Feb 1;15(3):761-4.
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22.
• [4] Pre-clinical and Clinical Safety Studies of CMX-2043: a cytoprotective lipoic acid analogue for ischaemia-reperfusion injury. Basic Clin Pharmacol Toxicol. 2014 Nov;115(5):456-64.
• [5] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [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: 1479).
• [7] CenterWatch. Drugs in Clinical Trials Database. CenterWatch. 2008.
• [8] The novel AKT inhibitor afuresertib shows favorable safety, pharmacokinetics, and clinical activity in multiple myeloma. Blood. 2014 Oct 2;124(14):2190-5.
• [9] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [10] 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.
• [11] Inhibiting the akt pathway in cancer treatment: three leading candidates. P T. 2011 Apr;36(4):225-7.
• [12] DOI: 10.1016/S1359-6349(10)71767-5
• [13] 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.
• [14] Targeting the phosphoinositide 3-kinase (PI3K) pathway in cancer
• [15] Phase 0 clinical chemoprevention trial of the Akt inhibitor SR13668. Cancer Prev Res (Phila). 2011 Mar;4(3):347-53.
• [16] 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.
• [17] 2,3,5-Trisubstituted pyridines as selective AKT inhibitors. Part II: Improved drug-like properties and kinase selectivity from azaindazoles. Bioorg Med Chem Lett. 2010 Jan 15;20(2):679-83.
• [18] Molecular pharmacology and antitumor activity of PHT-427, a novel Akt/phosphatidylinositide-dependent protein kinase 1 pleckstrin homology domain inhibitor. Mol Cancer Ther. 2010 Mar;9(3):706-17.