Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTLP57V)

• DTT Name: Adenosine deaminase (ADA)
• Synonyms: Adenosine aminohydrolase; ADA1
• Gene Name: ADA
• DTT Type: Successful target; [1]
• BioChemical Class: Carbon-nitrogen hydrolase
• UniProt ID: ADA_HUMAN
• TTD ID: T03661
• EC Number: EC 3.5.4.4
• Sequence:
  MAQTPAFDKPKVELHVHLDGSIKPETILYYGRRRGIALPANTAEGLLNVIGMDKPLTLPD
  FLAKFDYYMPAIAGCREAIKRIAYEFVEMKAKEGVVYVEVRYSPHLLANSKVEPIPWNQA
  EGDLTPDEVVALVGQGLQEGERDFGVKARSILCCMRHQPNWSPKVVELCKKYQQQTVVAI
  DLAGDETIPGSSLLPGHVQAYQEAVKSGIHRTVHAGEVGSAEVVKEAVDILKTERLGHGY
  HTLEDQALYNRLRQENMHFEICPWSSYLTGAWKPDTEHAVIRLKNDQANYSLNTDDPLIF
  KSTLDTDYQMTKRDMGFTEEEFKRLNINAAKSSFLPEDEKRELLDLLYKAYGMPPSASAG
  QNL
• Function: Plays an important role in purine metabolism and in adenosine homeostasis. Modulates signaling by extracellular adenosine, and so contributes indirectly to cellular signaling events. Acts as a positive regulator of T-cell coactivation, by binding DPP4. Its interaction with DPP4 regulates lymphocyte-epithelial cell adhesion. Enhances dendritic cell immunogenicity by affecting dendritic cell costimulatory molecule expression and cytokines and chemokines secretion. Enhances CD4+ T-cell differentiation and proliferation. Acts as a positive modulator of adenosine receptors ADORA1 and ADORA2A, by enhancing their ligand affinity via conformational change. Stimulates plasminogen activation. Plays a role in male fertility. Plays a protective role in early postimplantation embryonic development. Catalyzes the hydrolytic deamination of adenosine and 2-deoxyadenosine.
• KEGG Pathway:
  Purine metabolism (hsa00230)
  Metabolic pathways (hsa01100)
  Primary immunodeficiency (hsa05340)
• Reactome Pathway: Purine salvage (R-HSA-74217)
• BioCyc Pathway: MetaCyc:HS02191-MON

Molecular Interaction Atlas (MIA) of This DTT

4 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cladribine	DM3JDRP	Hairy cell leukaemia	2A82.2	Approved	[1]
Elapegademase	DMS7OU8	Adenosine deaminase defciency	4A01.1	Approved	[2]
Fludarabine	DMVRLT7	Acute myelogenous leukaemia	2A41	Approved	[3]
Pentostatin	DM0HXDS	Acute graft versus host disease	4B24.0	Approved	[3]

3 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
GSK2696273	DMP5O1U	Chronic pain	MG30	Preregistration	[4]
OTL-101	DMLMS6J	Severe combined immunodeficiency	4A01.10	Phase 3	[5]
Ex vivo adenosine deaminase-transduced hematopoietic stem cell therapy	DMIREUZ	Immunodeficiency	4A00-4A85	Phase 1/2	[4]

22 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(2S,3R)-3-(6-amino-9H-purin-9-yl)nonan-2-ol	DM4JQCR	Discovery agent	N.A.	Investigative	[6]
1-Deaza-Adenosine	DMG0VN6	Discovery agent	N.A.	Investigative	[7]
3-(6-Amino-purin-9-yl)-4-butoxy-butan-2-ol	DMISL9R	Discovery agent	N.A.	Investigative	[8]
3-(6-Amino-purin-9-yl)-4-p-tolyl-butan-2-ol	DMU08A4	Discovery agent	N.A.	Investigative	[8]
3-(6-Amino-purin-9-yl)-4-phenethyloxy-butan-2-ol	DMMTU78	Discovery agent	N.A.	Investigative	[8]
3-(6-Amino-purin-9-yl)-5-m-tolyl-pentan-2-ol	DMHXI21	Discovery agent	N.A.	Investigative	[8]
3-(6-Amino-purin-9-yl)-6-o-tolyl-hexan-2-ol	DMYIZBK	Discovery agent	N.A.	Investigative	[8]
3-(6-Amino-purin-9-yl)-6-phenyl-hexan-2-ol	DMZT8QX	Discovery agent	N.A.	Investigative	[8]
3-(6-Amino-purin-9-yl)-7-phenyl-heptan-2-ol	DMUYELJ	Discovery agent	N.A.	Investigative	[8]
3-(6-Amino-purin-9-yl)-8-phenyl-octan-2-ol	DMAIS1D	Discovery agent	N.A.	Investigative	[8]
3-(6-Amino-purin-9-yl)-non-5-en-2-ol	DM6FHWZ	Discovery agent	N.A.	Investigative	[8]
3-(6-Amino-purin-9-yl)-non-5-yn-2-ol	DM0YOZJ	Discovery agent	N.A.	Investigative	[8]
6-Hydroxy-1,6-Dihydro Purine Nucleoside	DMUD1CG	Discovery agent	N.A.	Investigative	[7]
6-Hydroxy-7,8-Dihydro Purine Nucleoside	DMNM1EZ	Discovery agent	N.A.	Investigative	[7]
EHNA	DM014WS	Discovery agent	N.A.	Investigative	[9]
FR117016	DM6UWVB	Discovery agent	N.A.	Investigative	[6]
FR221647	DM70UQR	Discovery agent	N.A.	Investigative	[6]
FR230513	DM3V0HA	Discovery agent	N.A.	Investigative	[6]
FR233623	DMR251H	Discovery agent	N.A.	Investigative	[6]
FR236913	DMLH546	Discovery agent	N.A.	Investigative	[6]
FR239087	DMMJDXT	Discovery agent	N.A.	Investigative	[6]
Purine Riboside	DMHNS0V	Discovery agent	N.A.	Investigative	[7]

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

• DTT DME Name: Adenosine aminohydrolase (ADA) DME Info
• Gene Name: ADA

2 Approved Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Adenosine	DMM2NSK	Paroxysmal supraventricular tachycardia	BC81.Z	Approved	[10]
Nelarabine	DMB6VEG	leukaemia	2A60-2B33	Approved	[11]

References

• [1] Cladribine: from the bench to the bedside--focus on hairy cell leukemia. Expert Rev Anticancer Ther. 2004 Oct;4(5):745-57.
• [2] 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
• [3] Purine nucleoside analogs in indolent non-Hodgkin's lymphoma. Oncology (Williston Park). 2000 Jun;14(6 Suppl 2):13-5.
• [4] Clinical pipeline report, company report or official report of GlaxoSmithKline.
• [5] Clinical pipeline report, company report or official report of Orchard Therapeutics.
• [6] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [7] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [8] Adenosine deaminase inhibitors: synthesis and biological evaluation of unsaturated, aromatic, and oxo derivatives of (+)-erythro-9-(2'S-hydroxy-3'R... J Med Chem. 2000 Nov 30;43(24):4694-700.
• [9] Tight-binding inhibitors--IV. Inhibition of adenosine deaminases by various inhibitors. Biochem Pharmacol. 1977 Mar 1;26(5):359-67.
• [10] A functional genetic variation of adenosine deaminase affects the duration and intensity of deep sleep in humans. Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15676-81.
• [11] Profile of nelarabine: use in the treatment of T-cell acute lymphoblastic leukemia. Onco Targets Ther. 2009 Feb 18;2:219-28.