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

General Information of Drug (ID: DMP8HW1)

• Drug Name: LY2157299 Drug Info
• Synonyms: Galunisertib; 700874-72-2; LY2157299; LY 2157299; LY-2157299; UNII-3OKH1W5LZE; 4-(2-(6-methylpyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)quinoline-6-carboxamide; 3OKH1W5LZE; Galunisertib (LY2157299); AK-79916; 4-[5,6-Dihydro-2-(6-methyl-2-pyridinyl)-4H-pyrrolo[1,2-b]pyrazol-3-yl]-6-quinolinecarboxamide; 4-(2-(6-Methylpyridin-2-yl)-5,6-dihydro-4H-pyrrolo-[1,2-b]pyrazol-3-yl)quinoline-6-carboxamide; 4-[2-(6-methylpyridin-2-yl)-4H,5H,6H-pyrrolo[1,2-b]pyrazol-3-yl]quinoline-6-carboxamide

Indication

Disease Entry	ICD 11	Status	REF
Arteriosclerosis	BD40	Phase 2/3	[1]
Non-small-cell lung cancer	2C25.Y	Phase 2/3	[2]
Hepatocellular carcinoma	2C12.02	Phase 2	[2]
Glioma	2A00.0	Phase 1/2	[3]
Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[2]
Pancreatic cancer	2C10	Phase 1	[2]

• Cross-matching ID:
  PubChem CID: 10090485
  ChEBI ID: CHEBI:137064
  CAS Number: CAS 700874-72-2
  TTD Drug ID: DMP8HW1

Molecule-Related Drug Atlas

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
TEW-7197	DM2LBC3	Myeloproliferative neoplasm	2A20	Phase 2	[5]
Metelimumab	DMENFD6	Scleroderma	4A42	Phase 1/2	[6]
TP-0184	DMJVZBC	Solid tumour/cancer	2A00-2F9Z	Phase 1	[7]
P-2745	DMJ3PNS	Chronic myelogenous leukaemia	2A20.0	Phase 1	[8]
LY3200882	DMQP6VB	Solid tumour/cancer	2A00-2F9Z	Phase 1	[2]
PF-06952229	DMDQJEZ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[9]
SB-431542	DM0YOXQ	Pulmonary fibrosis	CB03.4	Preclinical	[10]
SM-16	DMHXJV2	Fibrosis	GA14-GC01	Terminated	[11]
LF-984	DMIYMS2	Fibrosis	GA14-GC01	Terminated	[12]
PMID23639540C13d	DMSTQGH	Discovery agent	N.A.	Investigative	[13]

Drug(s) Targeting Transforming growth factor beta 1 (TGFB1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Pirfenidone	DM6VZFQ	Idiopathic pulmonary fibrosis	CB03.4	Approved	[14]
A435	DMJCL7X	Aggressive cancer	2A00-2F9Z	IND submitted	[15]
TG-C	DMLCXPD	Arthritis	FA20	Phase 3	[16]
Disitertide	DM2QBDS	Macular degeneration	9B78.3	Phase 2	[17]
SRK-181	DM0EWMT	Solid tumour/cancer	2A00-2F9Z	Phase 1	[18]
ABBV-151	DMIQXDJ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[19]
ACE-1334	DMF1OUP	Systemic sclerosis	4A42	Phase 1	[20]
Mannose phosphate	DM1LM7D	Lesion	8A00-8C12	Discontinued in Phase 2	[21]
ART-144	DMEVT4I	Osteoarthritis	FA00-FA05	Investigative	[22]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
TGF-beta receptor type I (TGFBR1)	TTP4520	TGFR1_HUMAN	Modulator	[4]
Transforming growth factor beta 1 (TGFB1)	TTR9XHZ	TGFB1_HUMAN	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: 7797).
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [4] 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.
• [5] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [6] Development of TGF-beta signalling inhibitors for cancer therapy. Nat Rev Drug Discov. 2004 Dec;3(12):1011-22.
• [7] Clinical pipeline report, company report or official report of Sumitomo Dainippon Pharma.
• [8] Novel potent inhibitor of Bcr-Abl mutated imatinib resistant chronic myeloid leukemia cell lines. Cancer Research. 06/2012; 72(8 Supplement):1822-1822.
• [9] Targeting the TGF pathway for cancer therapy. Pharmacol Ther. 2015 Mar;147:22-31.
• [10] Pyrazolone based TGFbetaR1 kinase inhibitors. Bioorg Med Chem Lett. 2010 Jan 1;20(1):326-9.
• [11] 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.
• [12] US patent application no. 2013,0028,978, Compositions and methods for wound treatment.
• [13] 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.
• [14] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [15] Clinical pipeline report, company report or official report of Klus Pharma
• [16] Clinical pipeline report, company report or official report of Tissue Gene, Inc.
• [17] Perspectives of TGF-beta inhibition in pancreatic and hepatocellular carcinomas. Oncotarget. 2014 January; 5(1): 78-94.
• [18] Clinical pipeline report, company report or official report of Scholar Rock.
• [19] Clinical pipeline report, company report or official report of AbbVie.
• [20] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2023. Adis Insight
• [21] The mannose-6-phosphate analogue, PXS64, inhibits fibrosis via TGF-beta1 pathway in human lung fibroblasts. Immunol Lett. 2015 Jun;165(2):90-101.
• [22] Pharmaceutical products of TORREYA partners. December 2011.