Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTAUX24)

• DTT Name: Erythropoietin Receptor (EPOR)
• Synonyms: Full-length form; EPO-R
• Gene Name: EPOR
• DTT Type: Successful target; [1]
• BioChemical Class: Cytokine receptor
• UniProt ID: EPOR_HUMAN
• TTD ID: T65197
• Sequence:
  MDHLGASLWPQVGSLCLLLAGAAWAPPPNLPDPKFESKAALLAARGPEELLCFTERLEDL
  VCFWEEAASAGVGPGNYSFSYQLEDEPWKLCRLHQAPTARGAVRFWCSLPTADTSSFVPL
  ELRVTAASGAPRYHRVIHINEVVLLDAPVGLVARLADESGHVVLRWLPPPETPMTSHIRY
  EVDVSAGNGAGSVQRVEILEGRTECVLSNLRGRTRYTFAVRARMAEPSFGGFWSAWSEPV
  SLLTPSDLDPLILTLSLILVVILVLLTVLALLSHRRALKQKIWPGIPSPESEFEGLFTTH
  KGNFQLWLYQNDGCLWWSPCTPFTEDPPASLEVLSERCWGTMQAVEPGTDDEGPLLEPVG
  SEHAQDTYLVLDKWLLPRNPPSEDLPGPGGSVDIVAMDEGSEASSCSSALASKPSPEGAS
  AASFEYTILDPSSQLLRPWTLCPELPPTPPHLKYLYLVVSDSGISTDYSSGDSQGAQGGL
  SDGPYSNPYENSLIPAAEPLPPSYVACS
• Function: Mediates erythropoietin-induced erythroblast proliferation and differentiation. Upon EPO stimulation, EPOR dimerizes triggering the JAK2/STAT5 signaling cascade. In some cell types, can also activate STAT1 and STAT3. May also activate the LYN tyrosine kinase. Receptor for erythropoietin.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  PI3K-Akt signaling pathway (hsa04151)
  Jak-STAT signaling pathway (hsa04630)
  Hematopoietic cell lineage (hsa04640)
• Reactome Pathway:
  Erythropoietin activates Phosphoinositide-3-kinase (PI3K) (R-HSA-9027276)
  Erythropoietin activates Phospholipase C gamma (PLCG) (R-HSA-9027277)
  Erythropoietin activates STAT5 (R-HSA-9027283)
  Erythropoietin activates RAS (R-HSA-9027284)
  Signaling by Erythropoietin (R-HSA-9006335)

Molecular Interaction Atlas (MIA) of This DTT

4 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Darbepoetin alfa	DMMJTYW	Anemia	3A00-3A9Z	Approved	[2]
Epoetin alfa	DMKWB73	Anemia	3A00-3A9Z	Approved	[1]
Methoxy polyethylene glycol-epoetin beta	DMK1LZD	Kidney transplant rejection	NE84	Approved	[3]
RHuEPO	DMALNG0	Solid tumour/cancer	2A00-2F9Z	Approved	[4]

4 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Epoetin zeta	DM9QPOU	Anemia	3A00-3A9Z	Phase 3	[5]
ErepoXen	DM9YI2C	Anemia	3A00-3A9Z	Phase 3	[6]
Hematide	DMUE843	Anemia	3A00-3A9Z	Phase 3	[7]
Cibinetide	DMCFLRH	Depression	6A70-6A7Z	Phase 2	[8]

2 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
GlycoPEGylated erythropoietin	DM5JKCL	Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 2	[9]
Albupoietin	DMXK4CI	Anemia	3A00-3A9Z	Terminated	[10]

10 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
3,5 DIBROMOTYROSINE	DMLIG3X	Discovery agent	N.A.	Investigative	[11]
BBT-009	DM2YTXL	Anemia	3A00-3A9Z	Investigative	[4]
BBT-021	DMLIT84	Anemia	3A00-3A9Z	Investigative	[4]
EPO peptide mimetics	DMP2QF0	Anemia	3A00-3A9Z	Investigative	[4]
EPO-derived peptide	DMHQDLX	Diabetic retinopathy	9B71.0	Investigative	[4]
Erythropoietin	DM3R8YL	Periventricular leukomalacia		Investigative	[4]
Nova-EPO	DM82DNL	Anemia	3A00-3A9Z	Investigative	[4]
P-1116	DMQ6TZE	Anemia	3A00-3A9Z	Investigative	[4]
PEG-EPO	DM5GVZJ	Anemia	3A00-3A9Z	Investigative	[4]
PT-401	DM736T8	Anemia	3A00-3A9Z	Investigative	[4]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Shwachman-Diamond syndrome	3B64	Bone marrow	7.04E-01	0.11	0.27

References

• [1] 2007 Standards, Options, and Recommendations: use of erythropoiesis-stimulating agents (ESA: epoetin alfa, epoetin beta, and darbepoetin) for the management of anemia in children with cancer. PediatrBlood Cancer. 2009 Jul;53(1):7-12.
• [2] A cytosolic domain of the erythropoietin receptor contributes to endoplasmic reticulum-associated degradation. Eur J Biochem. 1999 Jul;263(2):410-9.
• [3] 2007 FDA drug approvals: a year of flux. Nat Rev Drug Discov. 2008 Feb;7(2):107-9.
• [4] 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: 1718).
• [5] Long-term safety and tolerability of epoetin zeta, administered intravenously, for maintenance treatment of renal anemia. Adv Ther. 2008 Nov;25(11):1215-28.
• [6] Combination erythropoietin-hydroxyurea therapy in sickle cell disease: experience from the National Institutes of Health and a literature review. Haematologica. 2006 Aug;91(8):1076-83.
• [7] Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
• [8] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [9] Design of Homogeneous, MonoPEGylated Erythropoietin Analogs With Preserved In Vitro Bioactivity. Exp Hematol. 2006 June; 34(6): 697-704.
• [10] Clinical pipeline report, company report or official report of cogenesys.
• [11] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.