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

General Information of Drug (ID: DM3PVBJ)

• Drug Name: M2698 Drug Info
• Synonyms: HXAUJHZZPCBFPN-QGZVFWFLSA-N; 1379545-95-5; SCHEMBL15262358; EX-A1187; AKOS030627134; M2698(MSC-2363318A)

Indication

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

• Cross-matching ID:
  PubChem CID: 89808643
  CAS Number: CAS 1379545-95-5
  TTD Drug ID: DM3PVBJ

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]
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]
GSK690693	DMRBVHE	Haematological malignancy	2B33.Y	Phase 1	[17]

Drug(s) Targeting Ribosomal protein S6 kinase beta-1 (S6K1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
NNI-362	DMPCV65	Alzheimer disease	8A20	Phase 1	[18]
PF-4708671	DMO0892	Ulcerative colitis	DD71	Clinical trial	[19]
PMID27410995-Compound-Figure3c	DMDQMZT	N. A.	N. A.	Patented	[20]
Pyrimido[4,5-d] pyrimidines and pyrido[4,3-d] pyrimidine derivative 1	DM6O2Q9	N. A.	N. A.	Patented	[20]
RO-316233	DMAGLPW	Discovery agent	N.A.	Investigative	[21]
4-[(3,5-diamino-1H-pyrazol-4-yl)diazenyl]phenol	DMSKJ1X	Discovery agent	N.A.	Investigative	[22]
4,5,6,7-tetrabromo-1H-benzo[d][1,2,3]triazole	DMN9YOB	Discovery agent	N.A.	Investigative	[23]
CI-1040	DMF3DZX	Discovery agent	N.A.	Investigative	[21]
KN-62	DMLZ89P	Discovery agent	N.A.	Investigative	[21]
Ro31-8220	DMDJLF0	Discovery agent	N.A.	Investigative	[21]

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	[2]
RAC-gamma serine/threonine-protein kinase (AKT3)	TTAZ05C	AKT3_HUMAN	Inhibitor	[2]
Ribosomal protein S6 kinase beta-1 (S6K1)	TTG0U4H	KS6B1_HUMAN	Inhibitor	[2]

References

• [1] ClinicalTrials.gov (NCT01971515) First-in-Human Dose Escalation Trial in Subjects With Advanced Malignancies. U.S. National Institutes of Health.
• [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] Characterization of an Akt kinase inhibitor with potent pharmacodynamic and antitumor activity.Cancer Res.2008 Apr 1;68(7):2366-74.
• [18] Novel pharmacotherapy: NNI-362, an allosteric p70S6 kinase stimulator, reverses cognitive and neural regenerative deficits in models of aging and disease. Stem Cell Res Ther. 2021 Jan 13;12(1):59.
• [19] Characterization of PF-4708671, a novel and highly specific inhibitor of p70 ribosomal S6 kinase (S6K1). Biochem J. 2010 Oct 15;431(2):245-55.
• [20] Ribosomal S6 kinase (RSK) modulators: a patent review.Expert Opin Ther Pat. 2016 Sep;26(9):1061-78.
• [21] Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem J. 2000 Oct 1;351(Pt 1):95-105.
• [22] 4-arylazo-3,5-diamino-1H-pyrazole CDK inhibitors: SAR study, crystal structure in complex with CDK2, selectivity, and cellular effects. J Med Chem. 2006 Nov 2;49(22):6500-9.
• [23] Optimization of protein kinase CK2 inhibitors derived from 4,5,6,7-tetrabromobenzimidazole. J Med Chem. 2004 Dec 2;47(25):6239-47.