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

General Information of Drug (ID: DM2LBC3)

• Drug Name: TEW-7197 Drug Info
• Synonyms: Vactosertib

Indication

Disease Entry	ICD 11	Status	REF
Myeloproliferative neoplasm	2A20	Phase 2	[1]
Urothelial carcinoma	2C92.0	Phase 2	[2]
Myelodysplastic syndrome	2A37	Phase 1/2	[3]
Solid tumour/cancer	2A00-2F9Z	Phase 1	[4]

• Cross-matching ID:
  PubChem CID: 54766013
  CAS Number: CAS 1352608-82-2
  TTD Drug ID: DM2LBC3

Molecule-Related Drug Atlas

Drug(s) Targeting Transforming growth factor beta (TGFB)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
M7824	DMJCULI	Solid tumour/cancer	2A00-2F9Z	Phase 2	[3]
Bintrafusp alfa	DMB9LRJ	Non-small-cell lung cancer	2C25	Phase 2	[6]
NIS793	DM8LBYT	Pancreatic ductal carcinoma	2C10.0	Phase 2	[3]
LY2382770	DMH3YKJ	Diabetic kidney disease	GB61.Z	Phase 2	[7]
Fresolimumab	DMFZ084	Brain cancer	2A00	Phase 2	[8]
BCA101	DMM0VBU	Solid tumour/cancer	2A00-2F9Z	Phase 1	[9]
GS-1423	DMS25DL	Solid tumour/cancer	2A00-2F9Z	Phase 1	[10]
ACE-011	DMJ36YH	Anemia	3A00-3A9Z	Phase 1	[11]
AVID200	DMZ39T6	Solid tumour/cancer	2A00-2F9Z	Phase 1	[12]
RG6440	DMVQXFH	Aggressive cancer	2A00-2F9Z	Phase 1	[13]

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	[14]
Metelimumab	DMENFD6	Scleroderma	4A42	Phase 1/2	[15]
TP-0184	DMJVZBC	Solid tumour/cancer	2A00-2F9Z	Phase 1	[16]
P-2745	DMJ3PNS	Chronic myelogenous leukaemia	2A20.0	Phase 1	[17]
LY3200882	DMQP6VB	Solid tumour/cancer	2A00-2F9Z	Phase 1	[3]
PF-06952229	DMDQJEZ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[18]
SB-431542	DM0YOXQ	Pulmonary fibrosis	CB03.4	Preclinical	[19]
SM-16	DMHXJV2	Fibrosis	GA14-GC01	Terminated	[20]
LF-984	DMIYMS2	Fibrosis	GA14-GC01	Terminated	[21]
PMID23639540C13d	DMSTQGH	Discovery agent	N.A.	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	[5]
Transforming growth factor beta (TGFB)	TTO3HT7	NOUNIPROTAC	Antagonist	[3]

References

• [1] ClinicalTrials.gov (NCT04103645) Intra-patient Dose Escalation Study to Investigate Safety and Feasibility of Vactosertib in Treating Anemic MPN Patients. U.S. National Institutes of Health.
• [2] ClinicalTrials.gov (NCT04064190) Vactosertib With Durvalumab in Urothelial Carcinoma Failing Checkpoint Inhibition. U.S. National Institutes of Health.
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [4] ClinicalTrials.gov (NCT02160106) First in Human Dose Escalation Study of TEW-7197 in Subjects With Advanced Stage Solid Tumors. U.S. National Institutes of Health.
• [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] Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGF- and PD-L1, in Second-Line Treatment of Patients With NSCLC: Results From an Expansion Cohort of a Phase 1 Trial. J Thorac Oncol. 2020 Jul;15(7):1210-1222.
• [7] A phase I dose-escalation study to a predefined dose of a transforming growth factor-1 monoclonal antibody (TM1) in patients with metastatic cancer. Int J Oncol. 2014 Dec;45(6):2221-31.
• [8] Focal Irradiation and Systemic TGF Blockade in Metastatic Breast Cancer. Clin Cancer Res. 2018 Jun 1;24(11):2493-2504.
• [9] ClinicalTrials.gov (NCT04429542) Study of Safety and Tolerability of BCA101 Alone and in Combination With Pembrolizumab in Patients With EGFR-driven Advanced Solid Tumors. U.S. National Institutes of Health.
• [10] Clinical pipeline report, company report or official report of Agenus.
• [11] Clinical pipeline report, company report or official report of Acceleron Pharma (2011).
• [12] TGF signaling underlies hematopoietic dysfunction and bone marrow failure in Shwachman-Diamond Syndrome. J Clin Invest. 2019 Jun 18;129(9):3821-3826.
• [13] Clinical pipeline report, company report or official report of Roche
• [14] 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.
• [15] Development of TGF-beta signalling inhibitors for cancer therapy. Nat Rev Drug Discov. 2004 Dec;3(12):1011-22.
• [16] Clinical pipeline report, company report or official report of Sumitomo Dainippon Pharma.
• [17] Novel potent inhibitor of Bcr-Abl mutated imatinib resistant chronic myeloid leukemia cell lines. Cancer Research. 06/2012; 72(8 Supplement):1822-1822.
• [18] Targeting the TGF pathway for cancer therapy. Pharmacol Ther. 2015 Mar;147:22-31.
• [19] Pyrazolone based TGFbetaR1 kinase inhibitors. Bioorg Med Chem Lett. 2010 Jan 1;20(1):326-9.
• [20] 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.
• [21] US patent application no. 2013,0028,978, Compositions and methods for wound treatment.
• [22] 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.