Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTUS45N)

• DTT Name: Leukocyte common antigen (PTPRC)
• Synonyms: T200; Receptor-type tyrosine-protein phosphatase C; L-CA; CD45 antigen; CD45
• Gene Name: PTPRC
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Phosphoric monoester hydrolase
• UniProt ID: PTPRC_HUMAN
• TTD ID: T43115
• EC Number: EC 3.1.3.48
• Sequence:
  MTMYLWLKLLAFGFAFLDTEVFVTGQSPTPSPTGLTTAKMPSVPLSSDPLPTHTTAFSPA
  STFERENDFSETTTSLSPDNTSTQVSPDSLDNASAFNTTGVSSVQTPHLPTHADSQTPSA
  GTDTQTFSGSAANAKLNPTPGSNAISDVPGERSTASTFPTDPVSPLTTTLSLAHHSSAAL
  PARTSNTTITANTSDAYLNASETTTLSPSGSAVISTTTIATTPSKPTCDEKYANITVDYL
  YNKETKLFTAKLNVNENVECGNNTCTNNEVHNLTECKNASVSISHNSCTAPDKTLILDVP
  PGVEKFQLHDCTQVEKADTTICLKWKNIETFTCDTQNITYRFQCGNMIFDNKEIKLENLE
  PEHEYKCDSEILYNNHKFTNASKIIKTDFGSPGEPQIIFCRSEAAHQGVITWNPPQRSFH
  NFTLCYIKETEKDCLNLDKNLIKYDLQNLKPYTKYVLSLHAYIIAKVQRNGSAAMCHFTT
  KSAPPSQVWNMTVSMTSDNSMHVKCRPPRDRNGPHERYHLEVEAGNTLVRNESHKNCDFR
  VKDLQYSTDYTFKAYFHNGDYPGEPFILHHSTSYNSKALIAFLAFLIIVTSIALLVVLYK
  IYDLHKKRSCNLDEQQELVERDDEKQLMNVEPIHADILLETYKRKIADEGRLFLAEFQSI
  PRVFSKFPIKEARKPFNQNKNRYVDILPYDYNRVELSEINGDAGSNYINASYIDGFKEPR
  KYIAAQGPRDETVDDFWRMIWEQKATVIVMVTRCEEGNRNKCAEYWPSMEEGTRAFGDVV
  VKINQHKRCPDYIIQKLNIVNKKEKATGREVTHIQFTSWPDHGVPEDPHLLLKLRRRVNA
  FSNFFSGPIVVHCSAGVGRTGTYIGIDAMLEGLEAENKVDVYGYVVKLRRQRCLMVQVEA
  QYILIHQALVEYNQFGETEVNLSELHPYLHNMKKRDPPSEPSPLEAEFQRLPSYRSWRTQ
  HIGNQEENKSKNRNSNVIPYDYNRVPLKHELEMSKESEHDSDESSDDDSDSEEPSKYINA
  SFIMSYWKPEVMIAAQGPLKETIGDFWQMIFQRKVKVIVMLTELKHGDQEICAQYWGEGK
  QTYGDIEVDLKDTDKSSTYTLRVFELRHSKRKDSRTVYQYQYTNWSVEQLPAEPKELISM
  IQVVKQKLPQKNSSEGNKHHKSTPLLIHCRDGSQQTGIFCALLNLLESAETEEVVDIFQV
  VKALRKARPGMVSTFEQYQFLYDVIASTYPAQNGQVKKNNHQEDKIEFDNEVDKVKQDAN
  CVNPLGAPEKLPEAKEQAEGSEPTSGTEGPEHSVNGPASPALNQGS
• Function: Acts as a positive regulator of T-cell coactivation upon binding to DPP4. The first PTPase domain has enzymatic activity, while the second one seems to affect the substrate specificity of the first one. Upon T-cell activation, recruits and dephosphorylates SKAP1 and FYN. Dephosphorylates LYN, and thereby modulates LYN activity. Protein tyrosine-protein phosphatase required for T-cell activation through the antigen receptor.
• KEGG Pathway:
  Cell adhesion molecules (CAMs) (hsa04514)
  T cell receptor signaling pathway (hsa04660)
  Fc gamma R-mediated phagocytosis (hsa04666)
  Primary immunodeficiency (hsa05340)
• Reactome Pathway:
  Other semaphorin interactions (R-HSA-416700)
  Phosphorylation of CD3 and TCR zeta chains (R-HSA-202427)

Molecular Interaction Atlas (MIA) of This DTT

6 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
131I-labelled aCD45	DM3YEV0	Acute myeloid leukaemia	2A60	Phase 3	[2]
Iomab-B	DMZA47Y	Acute myeloid leukaemia	2A60	Phase 3	[1]
[131I]-BC8	DMV86DY	leukaemia	2A60-2B33	Phase 2	[3]
Anti-CD45 mabs	DMZ2D0G	Lymphoma	2A80-2A86	Phase 1	[4]
Iomab-ACT	DMY0QL7	B-cell acute lymphoblastic leukaemia	2B33.3	Phase 1	[5]
LM-CD45	DMR7LKC	Transplant rejection	NE84	Phase 1	[6]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
OX-30	DMVPG1N	Pain	MG30-MG3Z	Terminated	[7]

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Asp-BrPmp-Leu	DMJEZ62	Discovery agent	N.A.	Investigative	[8]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Acute myelocytic leukaemia	2C82	Bone marrow	5.86E-05	-0.26	-0.36

References

• [1] Clinical pipeline report, company report or official report of Actinium Pharmaceuticals.
• [2] 131I-anti-CD45 antibody plus busulfan and cyclophosphamide before allogeneic hematopoietic cell transplantation for treatment of acute myeloid leukemia in first remission. Blood. 2006 Mar 1;107(5):2184-91.
• [3] Development of a marrow transplant regimen for acute leukemia using targeted hematopoietic irradiation delivered by 131I-labeled anti-CD45 antibody, combined with cyclophosphamide and total body irradiation. Blood. 1995 Feb 15;85(4):1122-31.
• [4] CD45 monoclonal antibody-mediated cytolysis of human NK and T lymphoma cells. Haematologica. 2006 Jul;91(7):886-94.
• [5] Clinical pipeline report, company report or official report of Actinium Pharmaceuticals.
• [6] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002932)
• [7] CD45 / PTPRC Antibody, Biotin conjugate (OX-30).
• [8] A protected l-bromophosphonomethylphenylalanine amino acid derivative (BrPmp) for synthesis of irreversible protein tyrosine phosphatase inhibitors. Bioorg Med Chem. 2010 Dec 15;18(24):8679-86.