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

General Information of Drug (ID: DME0F5W)

• Drug Name: XL418 Drug Info

Indication

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

• Therapeutic Class: Anticancer Agents
• Cross-matching ID:
  PubChem CID: 56963011
  CAS Number: CAS 871343-09-8
  TTD Drug ID: DME0F5W

Molecule-Related Drug Atlas

Drug(s) Targeting Ribosomal protein S6 kinase (S6K)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
LYS-6KAKT1	DMLXGAI	Solid tumour/cancer	2A00-2F9Z	Phase 1	[3]
LY2780301	DM93AJW	Solid tumour/cancer	2A00-2F9Z	Phase 1	[4]
LY-2584702	DML8M3B	Solid tumour/cancer	2A00-2F9Z	Phase 1	[5]
PMID27410995-Compound-Figure3k	DMJ0QLB	N. A.	N. A.	Patented	[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	[7]
ARQ 092	DM5WK0J	Proteus syndrome	LD2C	Phase 2	[8]
MK-2206	DMT1OZ6	Rectal adenocarcinoma	2B92	Phase 2	[9]
GSK2141795	DMSHE70	Colorectal cancer	2B91.Z	Phase 2	[10]
M2698	DM3PVBJ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[11]
LYS-6KAKT1	DMLXGAI	Solid tumour/cancer	2A00-2F9Z	Phase 1	[3]
LY2780301	DM93AJW	Solid tumour/cancer	2A00-2F9Z	Phase 1	[4]
SR13668	DMO5760	Solid tumour/cancer	2A00-2F9Z	Phase 1	[12]
TCN-P	DMV0AH8	Acute myeloid leukaemia	2A60	Phase 1	[13]
GSK690693	DMRBVHE	Haematological malignancy	2B33.Y	Phase 1	[14]

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]
Ribosomal protein S6 kinase (S6K)	TT7M3PI	NOUNIPROTAC	Modulator	[2]

References

• [1] ClinicalTrials.gov (NCT00460278) Study of XL418 in Adults With Solid Tumors. U.S. National Institutes of Health.
• [2] Targeting the phosphoinositide 3-kinase (PI3K) pathway in cancer
• [3] DOI: 10.1016/S1359-6349(10)71767-5
• [4] 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.
• [5] A phase Ib trial of LY2584702 tosylate, a p70 S6 inhibitor, in combination with erlotinib or everolimus in patients with solid tumours.Eur J Cancer.2014 Mar;50(5):876-84.
• [6] Ribosomal S6 kinase (RSK) modulators: a patent review.Expert Opin Ther Pat. 2016 Sep;26(9):1061-78.
• [7] The novel AKT inhibitor afuresertib shows favorable safety, pharmacokinetics, and clinical activity in multiple myeloma. Blood. 2014 Oct 2;124(14):2190-5.
• [8] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [9] 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.
• [10] Inhibiting the akt pathway in cancer treatment: three leading candidates. P T. 2011 Apr;36(4):225-7.
• [11] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [12] Phase 0 clinical chemoprevention trial of the Akt inhibitor SR13668. Cancer Prev Res (Phila). 2011 Mar;4(3):347-53.
• [13] 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.
• [14] Characterization of an Akt kinase inhibitor with potent pharmacodynamic and antitumor activity.Cancer Res.2008 Apr 1;68(7):2366-74.