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

General Information of Drug (ID: DM57Z8J)

• Drug Name: LDN-214117 Drug Info
• Synonyms: compound 10 [PMID: 25101911]

Indication

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

• Cross-matching ID:
  PubChem CID: 91754554
  TTD Drug ID: DM57Z8J

Molecule-Related Drug Atlas

Drug(s) Targeting Activin receptor-like kinase 2 (ALK-2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
INCB00928	DMFG8TI	Anemia	3A00-3A9Z	Phase 2	[3]
TP-0184	DMJVZBC	Solid tumour/cancer	2A00-2F9Z	Phase 1	[4]
PMID27774822-Compound-Figure10Compound12	DMFAGOZ	N. A.	N. A.	Patented	[5]
PMID27774822-Compound-Figure10Compound4	DMMJVTW	N. A.	N. A.	Patented	[5]
PMID23639540C13d	DMSTQGH	Discovery agent	N.A.	Investigative	[6]
PMID23639540C13a	DMLXOAQ	Discovery agent	N.A.	Investigative	[6]
PMID23639540C13r	DMHBZ0N	Discovery agent	N.A.	Investigative	[6]
ML347	DMR8N36	Discovery agent	N.A.	Investigative	[6]

Drug(s) Targeting Activin receptor-like kinase-1 (ACVRL1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PF-03446962	DMTJWNE	Solid tumour/cancer	2A00-2F9Z	Phase 2	[7]
PMID23639540C13d	DMSTQGH	Discovery agent	N.A.	Investigative	[6]
PMID23639540C13a	DMLXOAQ	Discovery agent	N.A.	Investigative	[6]
PMID23639540C13r	DMHBZ0N	Discovery agent	N.A.	Investigative	[6]
ML347	DMR8N36	Discovery agent	N.A.	Investigative	[6]

Drug(s) Targeting TGF-beta receptor type I (TGFBR1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
LY2157299	DMP8HW1	Arteriosclerosis	BD40	Phase 2/3	[8]
TEW-7197	DM2LBC3	Myeloproliferative neoplasm	2A20	Phase 2	[9]
Metelimumab	DMENFD6	Scleroderma	4A42	Phase 1/2	[10]
TP-0184	DMJVZBC	Solid tumour/cancer	2A00-2F9Z	Phase 1	[4]
P-2745	DMJ3PNS	Chronic myelogenous leukaemia	2A20.0	Phase 1	[11]
LY3200882	DMQP6VB	Solid tumour/cancer	2A00-2F9Z	Phase 1	[12]
PF-06952229	DMDQJEZ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[13]
SB-431542	DM0YOXQ	Pulmonary fibrosis	CB03.4	Preclinical	[14]
SM-16	DMHXJV2	Fibrosis	GA14-GC01	Terminated	[15]
LF-984	DMIYMS2	Fibrosis	GA14-GC01	Terminated	[16]

Drug(s) Targeting Bone morphogenetic protein receptor (BMPR2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PMID23639540C13d	DMSTQGH	Discovery agent	N.A.	Investigative	[6]
PMID23639540C13a	DMLXOAQ	Discovery agent	N.A.	Investigative	[6]
PMID23639540C13r	DMHBZ0N	Discovery agent	N.A.	Investigative	[6]
ML347	DMR8N36	Discovery agent	N.A.	Investigative	[6]
AA-184	DMCN4ZD	Kidney injury	NB92.0	Investigative	[17]
AA-204	DMBGTX9	Kidney disease	GC2Z	Investigative	[17]
AA-123	DMW73A8	Prostate cancer	2C82.0	Investigative	[17]
AA-166	DM2BMAZ	Articular cartilage disorder	FA34.Y	Investigative	[17]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Activin receptor-like kinase 2 (ALK-2)	TTJNBQA	ACVR1_HUMAN	Inhibitor	[2]
Activin receptor-like kinase-1 (ACVRL1)	TTGYPTC	ACVL1_HUMAN	Inhibitor	[2]
Bone morphogenetic protein receptor (BMPR2)	TTGKF90	BMPR2_HUMAN	Inhibitor	[2]
TGF-beta receptor type I (TGFBR1)	TTP4520	TGFR1_HUMAN	Inhibitor	[2]

References

• [1] ACVR1 (587T>C) mutation in a variant form of fibrodysplasia ossificans progressiva: second report. Am J Med Genet A. 2014 Jan;164A(1):220-4.
• [2] Structure-activity relationship of 3,5-diaryl-2-aminopyridine ALK2 inhibitors reveals unaltered binding affinity for fibrodysplasia ossificans progressiva causing mutants. J Med Chem. 2014 Oct 9;57(19):7900-15.
• [3] Clinical pipeline report, company report or official report of Incyte.
• [4] Clinical pipeline report, company report or official report of Sumitomo Dainippon Pharma.
• [5] Inhibitors of JAK-family kinases: an update on the patent literature 2013-2015, part 2.Expert Opin Ther Pat. 2017 Feb;27(2):145-161.
• [6] Synthesis and structure-activity relationships of a novel and selective bone morphogenetic protein receptor (BMP) inhibitor derived from the pyrazolo[1.5-a]pyrimidine scaffold of dorsomorphin: the discovery of ML347 as an ALK2 versus ALK3 selective MLPCN probe. Bioorg Med Chem Lett. 2013 Jun 1;23(11):3248-52.
• [7] ALK1 as an emerging target for antiangiogenic therapy of cancer. Blood. 2011 June 30; 117(26): 6999-7006.
• [8] Cardiac Safety of TGF-beta Receptor I Kinase Inhibitor LY2157299 Monohydrate in Cancer Patients in a First-in-Human Dose Study. Cardiovasc Toxicol. 2015 Oct;15(4):309-23.
• [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] Development of TGF-beta signalling inhibitors for cancer therapy. Nat Rev Drug Discov. 2004 Dec;3(12):1011-22.
• [11] Novel potent inhibitor of Bcr-Abl mutated imatinib resistant chronic myeloid leukemia cell lines. Cancer Research. 06/2012; 72(8 Supplement):1822-1822.
• [12] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [13] Targeting the TGF pathway for cancer therapy. Pharmacol Ther. 2015 Mar;147:22-31.
• [14] Pyrazolone based TGFbetaR1 kinase inhibitors. Bioorg Med Chem Lett. 2010 Jan 1;20(1):326-9.
• [15] TGF-beta type I receptor kinase inhibitor down-regulates rheumatoid synoviocytes and prevents the arthritis induced by type II collagen antibody. Int Immunol. 2007 Feb;19(2):117-26.
• [16] US patent application no. 2013,0028,978, Compositions and methods for wound treatment.
• [17] 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: 1794).