Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTKLQTJ)

• DTT Name: Angiopoietin-2 (ANGPT2)
• Synonyms: ANG-2
• Gene Name: ANGPT2
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Fibrinogen protein
• UniProt ID: ANGP2_HUMAN
• TTD ID: T21960
• Sequence:
  MWQIVFFTLSCDLVLAAAYNNFRKSMDSIGKKQYQVQHGSCSYTFLLPEMDNCRSSSSPY
  VSNAVQRDAPLEYDDSVQRLQVLENIMENNTQWLMKLENYIQDNMKKEMVEIQQNAVQNQ
  TAVMIEIGTNLLNQTAEQTRKLTDVEAQVLNQTTRLELQLLEHSLSTNKLEKQILDQTSE
  INKLQDKNSFLEKKVLAMEDKHIIQLQSIKEEKDQLQVLVSKQNSIIEELEKKIVTATVN
  NSVLQKQQHDLMETVNNLLTMMSTSNSAKDPTVAKEEQISFRDCAEVFKSGHTTNGIYTL
  TFPNSTEEIKAYCDMEAGGGGWTIIQRREDGSVDFQRTWKEYKVGFGNPSGEYWLGNEFV
  SQLTNQQRYVLKIHLKDWEGNEAYSLYEHFYLSSEELNYRIHLKGLTGTAGKISSISQPG
  NDFSTKDGDNDKCICKCSQMLTGGWWFDACGPSNLNGMYYPQRQNTNKFNGIKWYYWKGS
  GYSLKATTMMIRPADF
• Function: Can induce tyrosine phosphorylation of TEK/TIE2 in the absence of ANGPT1. In the absence of angiogenic inducers, such as VEGF, ANGPT2-mediated loosening of cell-matrix contacts may induce endothelial cell apoptosis with consequent vascular regression. In concert with VEGF, it may facilitate endothelial cell migration and proliferation, thus serving as a permissive angiogenic signal. Binds to TEK/TIE2, competing for the ANGPT1 binding site, and modulating ANGPT1 signaling.
• KEGG Pathway:
  Ras signaling pathway (hsa04014)
  Rap1 signaling pathway (hsa04015)
  HIF-1 signaling pathway (hsa04066)
  PI3K-Akt signaling pathway (hsa04151)
• Reactome Pathway: Tie2 Signaling (R-HSA-210993)

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Faricimab	DM83SEB	Diabetic macular edema	9B71.02	Approved	[2]

12 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AMG 386	DMQJXL4	Breast cancer	2C60-2C65	Phase 3	[1]
Trebananib	DMOG2X1	Ovarian cancer	2C73	Phase 3	[3]
REGN910-3	DMTBRPO	Neovascular age-related macular degeneration	9B78.3Z	Phase 2	[5]
RG7221	DM8J9DC	Colorectal cancer	2B91.Z	Phase 2	[6]
RO5520985	DMD3WNP	Colorectal cancer	2B91.Z	Phase 2	[7]
CVX-060	DM03LWZ	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[8]
BI 836880	DMRI6YT	Neoplasm	2A00-2F9Z	Phase 1	[9]
CVX-241	DMV74JC	Solid tumour/cancer	2A00-2F9Z	Phase 1	[10]
MEDI3617	DM0H5JD	Ovarian cancer	2C73	Phase 1	[11]
Nesvacumab	DM59ZDN	Solid tumour/cancer	2A00-2F9Z	Phase 1	[12]
REGN-910	DMHR7D4	Solid tumour/cancer	2A00-2F9Z	Phase 1	[13]
Zifibancimig	DMIJ2MZ	Neovascular age-related macular degeneration	9B78.3Z	Phase 1	[14]

1 Drugs in Phase 2 Trial Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
LY3127804	DMAC457	Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 2 Trial	[4]

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ABTAA	DM79DSN	Sepsis	1G40-1G41	Investigative	[15]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Breast cancer	2C82	Breast tissue	3.47E-04	-0.31	-0.4
Rectal cancer	2C82	Rectal colon tissue	1.74E-02	1.13	1.66

References

• [1] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [2] Faricimab: an investigational agent targeting the Tie-2/angiopoietin pathway and VEGF-A for the treatment of retinal diseases. Expert Opin Investig Drugs. 2021 Mar;30(3):193-200.
• [3] Pediatric Phase I Trial and Pharmacokinetic Study of Trebananib in Relapsed Solid Tumors, Including Primary Tumors of the Central Nervous System ADVL1115: A Children's Oncology Group Phase I Consortium Report. Clin Cancer Res. 2017 Oct 15;23(20):6062-6069.
• [4] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [5] ClinicalTrials.gov (NCT02713204) Anti-angiOpoeitin 2 Plus Anti-vascular eNdothelial Growth Factor as a therapY for Neovascular Age Related Macular Degeneration: Evaluation of a fiXed Combination Intravitreal Injection (ONYX). U.S. National Institutes of Health.
• [6] Company report (Roche pipeline: July 27, 2017)
• [7] Bispecific antibodies rise again. Nat Rev Drug Discov. 2014 Nov;13(11):799-801.
• [8] Clinical pipeline report, company report or official report of CovX (2011).
• [9] Clinical pipeline report, company report or official report of Boehringer Ingelheim.
• [10] Chemical generation of bispecific antibodies. Proc Natl Acad Sci U S A. 2010 December 28; 107(52): 22611-22616.
• [11] Phase I Study of MEDI3617, a Selective Angiopoietin-2 Inhibitor Alone and Combined with Carboplatin/Paclitaxel, Paclitaxel, or Bevacizumab for Advanced Solid Tumors. Clin Cancer Res. 2018 Jun 15;24(12):2749-2757.
• [12] Tie-2/Angiopoietin pathway modulation as a therapeutic strategy for retinal disease. Expert Opin Investig Drugs. 2019 Oct;28(10):861-869.
• [13] Angiopoietin-2 functions as a Tie2 agonist in tumor models, where it limits the effects of VEGF inhibition. Cancer Res. 2013 Jan 1;73(1):108-18.
• [14] Clinical pipeline report, company report or official report of Roche
• [15] Amelioration of sepsis by TIE2 activation-induced vascular protection. Sci Transl Med. 2016 Apr 20;8(335):335ra55.