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

General Information of DTT (ID: TTP4520)

• DTT Name: TGF-beta receptor type I (TGFBR1) DTT Info
• Gene Name: TGFBR1

Molecule-Related Drug & Molecule List

7 Clinical Trial Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
LY2157299	DMP8HW1	Arteriosclerosis	BD40	Phase 2/3	[1]
TEW-7197	DM2LBC3	Myeloproliferative neoplasm	2A20	Phase 2	[2]
Metelimumab	DMENFD6	Scleroderma	4A42	Phase 1/2	[3]
LY3200882	DMQP6VB	Solid tumour/cancer	2A00-2F9Z	Phase 1	[4]
P-2745	DMJ3PNS	Chronic myelogenous leukaemia	2A20.0	Phase 1	[5]
PF-06952229	DMDQJEZ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[6]
TP-0184	DMJVZBC	Solid tumour/cancer	2A00-2F9Z	Phase 1	[7]

1 Preclinical Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
SB-431542	DM0YOXQ	Pulmonary fibrosis	CB03.4	Preclinical	[8]

2 Discontinued Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
LF-984	DMIYMS2	Fibrosis	GA14-GC01	Terminated	[9]
SM-16	DMHXJV2	Fibrosis	GA14-GC01	Terminated	[10]

22 Investigative Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
2-phenyl-N-(pyridin-4-yl)quinazolin-4-amine	DMEFOV6	Discovery agent	N.A.	Investigative	[11]
4-Pyridin-2-yl-5-quinolin-2-yl-thiazol-2-ylamine	DMY8ZLM	Discovery agent	N.A.	Investigative	[12]
4-Pyridin-2-yl-5-quinolin-4-yl-thiazol-2-ylamine	DM6RVB3	Discovery agent	N.A.	Investigative	[12]
4-Pyridin-3-yl-5-quinolin-4-yl-thiazol-2-ylamine	DM06AV8	Discovery agent	N.A.	Investigative	[12]
5''-Quinolin-4-yl-[2,4'']bithiazolyl-2''-ylamine	DMNYQGS	Discovery agent	N.A.	Investigative	[12]
ACE-435	DMOJGF3	Cachexia	MG20	Investigative	[13]
DRP-049	DMBUH02	Fibrosis	GA14-GC01	Investigative	[13]
GW-788388	DMIBUW5	Solid tumour/cancer	2A00-2F9Z	Investigative	[14]
HTS-466284	DM70YTF	Discovery agent	N.A.	Investigative	[15]
IN-1130	DM3YJXF	Discovery agent	N.A.	Investigative	[16]
IN-1166	DMMS6D3	Discovery agent	N.A.	Investigative	[17]
LDN-214117	DM57Z8J	Discovery agent	N.A.	Investigative	[18]
LY2109761	DMAWTG3	Discovery agent	N.A.	Investigative	[19]
PMID16539403C15b	DMU2X59	Discovery agent	N.A.	Investigative	[20]
PMID23639540C13d	DMSTQGH	Discovery agent	N.A.	Investigative	[21]
PMID23639540C13r	DMHBZ0N	Discovery agent	N.A.	Investigative	[21]
PTL-101	DMAEL4C	Pulmonary fibrosis	CB03.4	Investigative	[13]
SB-505124	DM4G09S	Discovery agent	N.A.	Investigative	[22]
SB-525334	DM0PETL	Discovery agent	N.A.	Investigative	[22]
SD-208	DMQXUYH	Discovery agent	N.A.	Investigative	[23]
TGF-beta Shield	DMUP34S	Solid tumour/cancer	2A00-2F9Z	Investigative	[13]
WilVent	DMZ703W	Pulmonary disease	1B10-1F85	Investigative	[13]

References

• [1] 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.
• [2] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [3] Development of TGF-beta signalling inhibitors for cancer therapy. Nat Rev Drug Discov. 2004 Dec;3(12):1011-22.
• [4] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [5] Novel potent inhibitor of Bcr-Abl mutated imatinib resistant chronic myeloid leukemia cell lines. Cancer Research. 06/2012; 72(8 Supplement):1822-1822.
• [6] Targeting the TGF pathway for cancer therapy. Pharmacol Ther. 2015 Mar;147:22-31.
• [7] Clinical pipeline report, company report or official report of Sumitomo Dainippon Pharma.
• [8] Pyrazolone based TGFbetaR1 kinase inhibitors. Bioorg Med Chem Lett. 2010 Jan 1;20(1):326-9.
• [9] US patent application no. 2013,0028,978, Compositions and methods for wound treatment.
• [10] 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.
• [11] Design of novel quinazoline derivatives and related analogues as potent and selective ALK5 inhibitors. Bioorg Med Chem Lett. 2009 Apr 15;19(8):2277-81.
• [12] Identification of 1,5-naphthyridine derivatives as a novel series of potent and selective TGF-beta type I receptor inhibitors. J Med Chem. 2004 Aug 26;47(18):4494-506.
• [13] 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: 1788).
• [14] Discovery of 4-{4-[3-(pyridin-2-yl)-1H-pyrazol-4-yl]pyridin-2-yl}-N-(tetrahydro-2H- pyran-4-yl)benzamide (GW788388): a potent, selective, and orall... J Med Chem. 2006 Apr 6;49(7):2210-21.
• [15] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [16] Synthesis and biological evaluation of 4(5)-(6-methylpyridin-2-yl)imidazoles and -pyrazoles as transforming growth factor-beta type 1 receptor kina... Bioorg Med Chem. 2010 Jun 15;18(12):4459-67.
• [17] Synthesis and biological evaluation of 4(5)-(6-alkylpyridin-2-yl)imidazoles as transforming growth factor-beta type 1 receptor kinase inhibitors. J Med Chem. 2007 Jun 28;50(13):3143-7.
• [18] 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.
• [19] LY2109761, a novel transforming growth factor beta receptor type I and type II dual inhibitor, as a therapeutic approach to suppressing pancreatic cancer metastasis. Mol Cancer Ther. 2008 Apr;7(4):829-40.
• [20] Dihydropyrrolopyrazole transforming growth factor-beta type I receptor kinase domain inhibitors: a novel benzimidazole series with selectivity vers... J Med Chem. 2006 Mar 23;49(6):2138-42.
• [21] 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.
• [22] Synthesis and biological evaluation of 2-pyridyl-substituted pyrazoles and imidazoles as transforming growth factor-beta type 1 receptor kinase inhibitors, Bioorg. Med. Chem. Lett. 20(14):4228-4232 (2010).
• [23] Evaluation of the anti-hepatitis C virus effect of novel potent, selective, and orally bioavailable JNK and VEGFR kinase inhibitors. Bioorg Med Chem Lett. 2007 Apr 1;17(7):1843-9.