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

General Information of Drug (ID: DM0164B)

• Drug Name: NSC-686549 Drug Info
• Synonyms: NSC686549

Indication

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

• Cross-matching ID:
  PubChem CID: 389898
  CAS Number: CAS 623163-52-0
  TTD Drug ID: DM0164B

Molecule-Related Drug Atlas

Drug(s) Targeting MAPK/ERK kinase kinase (MAP3K)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ARRY-162	DM1P6FR	Melanoma	2C30	Approved	[3]
Trametinib	DM2JGQ3	Melanoma	2C30	Approved	[4]
BAY 86-9766	DMPW5SB	Solid tumour/cancer	2A00-2F9Z	Phase 3	[5]
Selumetinib	DMC7W6R	Neurofibromatosis type 1	LD2D.10	Phase 3	[6]
MSC1936369B	DMH1DYU	Colorectal cancer	2B91.Z	Phase 2	[7]
RO-5126766	DM3U9BY	Non-small-cell lung cancer	2C25	Phase 2	[8]
E6201	DMOSL9P	Psoriasis vulgaris	EA90	Phase 2	[9]
PD-0325901	DM27D4J	Breast cancer	2C60-2C65	Phase 2	[3]
WX-554	DMRABOS	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[3]
RG7304	DMGFAVQ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[10]

Drug(s) Targeting Cot oncogene messenger RNA (MAP3K8 mRNA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
8-chloro-quinoline-3-carbonitrile	DMFNUHQ	Discovery agent	N.A.	Investigative	[11]
ISIS 116361	DMWBQHS	Discovery agent	N.A.	Investigative	[12]
Tpl2 kinase inhibitor	DMHATCZ	Discovery agent	N.A.	Investigative	[13]
ISIS 116414	DM4Q3JO	Discovery agent	N.A.	Investigative	[12]
ISIS 116360	DMFEZHM	Discovery agent	N.A.	Investigative	[12]
ISIS 116359	DM280AE	Discovery agent	N.A.	Investigative	[12]
ISIS 116362	DM7M1UB	Discovery agent	N.A.	Investigative	[12]
ISIS 116363	DMXKAJP	Discovery agent	N.A.	Investigative	[12]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Cot oncogene messenger RNA (MAP3K8 mRNA)	TTGECUM	M3K8_HUMAN	Inhibitor	[2]
MAPK/ERK kinase kinase (MAP3K)	TTROQ37	NOUNIPROTAC	Inhibitor	[2]

References

• [1] 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. (Ligand id: 6007).
• [2] A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases. Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20523-8.
• [3] MEK and the inhibitors: from bench to bedside. J Hematol Oncol. 2013; 6: 27.
• [4] Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
• [5] RDEA119/BAY 869766: a potent, selective, allosteric inhibitor of MEK1/2 for the treatment of cancer.Cancer Res.2009 Sep 1;69(17):6839-47.
• [6] Intrinsic resistance to selumetinib, a selective inhibitor of MEK1/2, by cAMP-dependent protein kinase A activation in human lung and colorectal cancer cells.Br J Cancer.2012 May 8;106(10):1648-59.
• [7] Antitumor activity of pimasertib, a selective MEK 1/2 inhibitor, in combination with PI3K/mTOR inhibitors or with multi-targeted kinase inhibitors in pimasertib-resistant human lung and colorectal cancer cells. Int J Cancer. 2013 Nov;133(9):2089-101.
• [8] The dual RAF/MEK inhibitor CH5126766/RO5126766 may be a potential therapy for RAS-mutated tumor cells.PLoS One.2014 Nov 25;9(11):e113217.
• [9] E6201, a novel kinase inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase-1 and mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase-1: in vivo effects on cutaneous inflammatory responses by topical administration. J Pharmacol Exp Ther. 2010 Oct;335(1):23-31.
• [10] Clinical pipeline report, company report or official report of Roche.
• [11] Pharmacologic inhibition of tpl2 blocks inflammatory responses in primary human monocytes, synoviocytes, and blood. J Biol Chem. 2007 Nov 16;282(46):33295-304.
• [12] US patent application no. 6,265,216, Antisense modulation of cot oncogene expression.
• [13] Inhibition of Tpl2 kinase and TNF-alpha production with 1,7-naphthyridine-3-carbonitriles: synthesis and structure-activity relationships. Bioorg Med Chem Lett. 2005 Dec 1;15(23):5288-92.