Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTIHYA4)

• DTT Name: Thrombopoietin receptor (MPL)
• Synonyms: TPOR; TPO-R; Proto-oncogene c-Mpl; Myeloproliferative leukemia protein; CD110 antigen; CD110; C-mpl
• Gene Name: MPL
• DTT Type: Successful target; [1]
• BioChemical Class: Cytokine receptor
• UniProt ID: TPOR_HUMAN
• TTD ID: T16156
• Sequence:
  MPSWALFMVTSCLLLAPQNLAQVSSQDVSLLASDSEPLKCFSRTFEDLTCFWDEEEAAPS
  GTYQLLYAYPREKPRACPLSSQSMPHFGTRYVCQFPDQEEVRLFFPLHLWVKNVFLNQTR
  TQRVLFVDSVGLPAPPSIIKAMGGSQPGELQISWEEPAPEISDFLRYELRYGPRDPKNST
  GPTVIQLIATETCCPALQRPHSASALDQSPCAQPTMPWQDGPKQTSPSREASALTAEGGS
  CLISGLQPGNSYWLQLRSEPDGISLGGSWGSWSLPVTVDLPGDAVALGLQCFTLDLKNVT
  CQWQQQDHASSQGFFYHSRARCCPRDRYPIWENCEEEEKTNPGLQTPQFSRCHFKSRNDS
  IIHILVEVTTAPGTVHSYLGSPFWIHQAVRLPTPNLHWREISSGHLELEWQHPSSWAAQE
  TCYQLRYTGEGHQDWKVLEPPLGARGGTLELRPRSRYRLQLRARLNGPTYQGPWSSWSDP
  TRVETATETAWISLVTALHLVLGLSAVLGLLLLRWQFPAHYRRLRHALWPSLPDLHRVLG
  QYLRDTAALSPPKATVSDTCEEVEPSLLEILPKSSERTPLPLCSSQAQMDYRRLQPSCLG
  TMPLSVCPPMAESGSCCTTHIANHSYLPLSYWQQP
• Function: May represent a regulatory molecule specific for TPO-R-dependent immune responses. Receptor for thrombopoietin that acts as a primary regulator of megakaryopoiesis and platelet production.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  Jak-STAT signaling pathway (hsa04630)
• Reactome Pathway: Platelet Aggregation (Plug Formation) (R-HSA-76009)

Molecular Interaction Atlas (MIA) of This DTT

4 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AS-1670542	DMV05SW	Thrombocytopenia	3B64	Approved	[2]
Eltrombopag	DMOGFIX	Thrombocytopenia	3B64	Approved	[1]
Lusutrombopag	DMH6IKO	Thrombocytopenia	3B64	Approved	[3]
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[4]

3 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
LGD-4665	DM9T8A2	Immune thrombocytopenic purpura	3B64.13	Phase 2	[1]
BVI-007	DM43GPX	Myocardial infarction	BA41-BA43	Phase 1	[2]
NIP-004	DM0PYEQ	Thrombocytopenia	3B64	Phase 1	[5]

3 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
RhTPO	DMCV0BZ	Idiopathic thrombocytopenic purpura	3B64.10	Discontinued in Phase 3	[1]
Totrombopag	DM6SUDC	Thrombocytopenia	3B64	Discontinued in Phase 1	[6]
Promegapoietin	DMS4FG0	Bone marrow transplantation	QB63.6	Terminated	[7]

7 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
HL-034	DMMW0OF	Discovery agent	N.A.	Investigative	[2]
Non-peptide TPO mimics	DMZ2DSK	Thrombocytopenia	3B64	Investigative	[2]
RI-TPO	DMJD3WY	Discovery agent	N.A.	Investigative	[8]
SB-559457	DM0OLYF	Acute myeloid leukaemia	2A60	Investigative	[2]
SE-ET-TP020d	DMCQNT9	Thrombocytopenia	3B64	Investigative	[8]
STS-T4	DM5BATX	Thrombocytopenia	3B64	Investigative	[2]
ThromboMer	DMRVXH7	Thrombocytopenia	3B64	Investigative	[2]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Sarcoma	2C82	Muscle tissue	1.03E-38	-0.17	-0.79
Thrombocytopenia	3B64	Whole blood	8.96E-01	0.07	0.28
Acute myelocytic leukaemia	2C82	Bone marrow	2.61E-06	0.1	0.45

References

• [1] Emerging drugs for idiopathic thrombocytopenic purpura in adults. Expert Opin Emerg Drugs. 2008 Jun;13(2):237-54.
• [2] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1722).
• [3] 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
• [4] 2008 FDA drug approvals. Nat Rev Drug Discov. 2009 Feb;8(2):93-6.
• [5] A novel nonpeptidyl human c-Mpl activator stimulates human megakaryopoiesis and thrombopoiesis. Blood. 2006 Jun 1;107(11):4300-7.
• [6] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [7] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [8] The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.