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

General Information of Drug (ID: DMY4B6J)

• Drug Name: BI-847325 Drug Info

Indication

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

• Cross-matching ID:
  PubChem CID: 135567102
  TTD Drug ID: DMY4B6J

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 Aurora kinase B (AURKB)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AT9283	DMQ94CT	Solid tumour/cancer	2A00-2F9Z	Phase 3	[11]
PHA-739358	DMGYBZI	Prostate cancer	2C82.0	Phase 2	[12]
VX-680	DM93YKJ	Solid tumour/cancer	2A00-2F9Z	Phase 2	[13]
ABT-348	DMMZOYN	Haematological malignancy	2B33.Y	Phase 2	[14]
HPP-607	DM5VSZR	Solid tumour/cancer	2A00-2F9Z	Phase 1	[15]
CYC116	DMUMHXT	Solid tumour/cancer	2A00-2F9Z	Phase 1	[16]
AMG 900	DMASGXJ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[17]
SNS-314	DMAC5F2	Solid tumour/cancer	2A00-2F9Z	Phase 1	[18]
R763	DME0CJ9	Haematological malignancy	2B33.Y	Phase 1	[19]
GSK1070916	DMXRPT6	Advanced solid tumour	2A00-2F9Z	Phase 1	[20]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Aurora kinase B (AURKB)	TT5LS6T	AURKB_HUMAN	Modulator	[2]
MAPK/ERK kinase kinase (MAP3K)	TTROQ37	NOUNIPROTAC	Modulator	[2]

References

• [1] ClinicalTrials.gov (NCT01324830) Monotherapy Dose Finding With BI 847325 in Solid Tumours. U.S. National Institutes of Health.
• [2] doi: 10.1158/1535-7163.TARG-13-B281
• [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] A phase I trial of AT9283 (a selective inhibitor of aurora kinases) in children and adolescents with solid tumors: a Cancer Research UK study. Clin Cancer Res. 2015 Jan 15;21(2):267-73.
• [12] Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
• [13] 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.
• [14] Preclinical characterization of ABT-348, a kinase inhibitor targeting the aurora, vascular endothelial growth factor receptor/platelet-derived growth factor receptor, and Src kinase families. J Pharmacol Exp Ther. 2012 Dec;343(3):617-27.
• [15] 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: 1936).
• [16] Clinical pipeline report, company report or official report of Cyclacel.
• [17] Preclinical evaluation of AMG 900, a novel potent and highly selective pan-aurora kinase inhibitor with activity in taxane-resistant tumor cell lines. Cancer Res. 2010 Dec 1;70(23):9846-54.
• [18] SNS-314, a pan-Aurora kinase inhibitor, shows potent anti-tumor activity and dosing flexibility in vivo. Cancer Chemother Pharmacol. 2010 Mar;65(4):707-17.
• [19] Preclinical characterization of Aurora kinase inhibitor R763/AS703569 identified through an image-based phenotypic screen. J Cancer Res Clin Oncol. 2010 Jan;136(1):99-113.
• [20] Discovery of GSK1070916, a potent and selective inhibitor of Aurora B/C kinase. J Med Chem. 2010 May 27;53(10):3973-4001.