Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTUI5H7)

• DTT Name: Angiotensin-converting enzyme 2 (ACE2)
• Synonyms: Processed angiotensinconverting enzyme 2; Metalloprotease MPROT15; Angiotensinconverting enzyme homolog; Angiotensinconverting enzyme 2; ACErelated carboxypeptidase; ACEH; ACE2
• Gene Name: ACE2
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Peptidase
• UniProt ID: ACE2_HUMAN
• TTD ID: T27889
• EC Number: EC 3.4.17.23
• Sequence:
  MSSSSWLLLSLVAVTAAQSTIEEQAKTFLDKFNHEAEDLFYQSSLASWNYNTNITEENVQ
  NMNNAGDKWSAFLKEQSTLAQMYPLQEIQNLTVKLQLQALQQNGSSVLSEDKSKRLNTIL
  NTMSTIYSTGKVCNPDNPQECLLLEPGLNEIMANSLDYNERLWAWESWRSEVGKQLRPLY
  EEYVVLKNEMARANHYEDYGDYWRGDYEVNGVDGYDYSRGQLIEDVEHTFEEIKPLYEHL
  HAYVRAKLMNAYPSYISPIGCLPAHLLGDMWGRFWTNLYSLTVPFGQKPNIDVTDAMVDQ
  AWDAQRIFKEAEKFFVSVGLPNMTQGFWENSMLTDPGNVQKAVCHPTAWDLGKGDFRILM
  CTKVTMDDFLTAHHEMGHIQYDMAYAAQPFLLRNGANEGFHEAVGEIMSLSAATPKHLKS
  IGLLSPDFQEDNETEINFLLKQALTIVGTLPFTYMLEKWRWMVFKGEIPKDQWMKKWWEM
  KREIVGVVEPVPHDETYCDPASLFHVSNDYSFIRYYTRTLYQFQFQEALCQAAKHEGPLH
  KCDISNSTEAGQKLFNMLRLGKSEPWTLALENVVGAKNMNVRPLLNYFEPLFTWLKDQNK
  NSFVGWSTDWSPYADQSIKVRISLKSALGDKAYEWNDNEMYLFRSSVAYAMRQYFLKVKN
  QMILFGEEDVRVANLKPRISFNFFVTAPKNVSDIIPRTEVEKAIRMSRSRINDAFRLNDN
  SLEFLGIQPTLGPPNQPPVSIWLIVFGVVMGVIVVGIVILIFTGIRDRKKKNKARSGENP
  YASIDISKGENNPGFQNTDDVQTSF
• Function: Carboxypeptidase which converts angiotensin I to angiotensin 1-9, a peptide of unknown function, and angiotensin II to angiotensin 1-7, a vasodilator. Also able to hydrolyze apelin- 13 and dynorphin-13 with high efficiency. May be an important regulator of heart function. In case of human coronaviruses SARS and HCoV-NL63 infections, serve as functional receptor for the spike glycoprotein of both coronaviruses.
• KEGG Pathway:
  Renin-angiotensin system (hsa04614)
  Protein digestion and absorption (hsa04974)
• Reactome Pathway: Metabolism of Angiotensinogen to Angiotensins (R-HSA-2022377)

Molecular Interaction Atlas (MIA) of This DTT

2 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
GSK2586881	DMU5EVR	Acute lung injury	NB32.3	Phase 2	[1]
ORE-1001	DM471ZH	Diabetic complication	5A2Y	Phase 1/2	[2]

2 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PMID18324760C28	DMCTFWE	Discovery agent	N.A.	Investigative	[3]
XNT	DMPOGXU	Discovery agent	N.A.	Investigative	[4]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Type 2 diabetes	5A11	Liver tissue	3.93E-02	0.4	1.1

The Drug-Metabolizing Enzyme (DME) Role of This DTT

• DTT DME Name: Angiotensin-converting enzyme 2 (ACE2) DME Info
• Gene Name: ACE2

2 Clinical Trial Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Angiotensin-(1-7)	DM76GZ0	Sarcoma	2A60-2C35	Phase 3	[5]
BRADYKININ	DM4R6UV	N. A.	N. A.	Phase 1	[6]

References

• [1] New Developments in the Pharmacological Treatment of Hypertension: Dead-End or a Glimmer at the Horizon . Curr Hypertens Rep. 2015; 17(6): 42.
• [2] Effects of the ACE2 inhibitor GL1001 on acute dextran sodium sulfate-induced colitis in mice. Inflamm Res. 2009 Nov;58(11):819-27.
• [3] Development of potent and selective phosphinic peptide inhibitors of angiotensin-converting enzyme 2. J Med Chem. 2008 Apr 10;51(7):2216-26.
• [4] Structure-based identification of small-molecule angiotensin-converting enzyme 2 activators as novel antihypertensive agents. Hypertension. 2008 May;51(5):1312-7.
• [5] Metabolism of angiotensin-(1-7) by angiotensin-converting enzyme. Hypertension. 1998 Jan;31(1 Pt 2):362-7.
• [6] Nunn's Applied Respiratory Physiology (Eighth Edition). Chapter 11 - Nonrespiratory Functions of the Lung.2017, Pages 203-214.e2