Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTENHJ0)

• DTT Name: Interleukin 3 receptor alpha (IL3RA)
• Synonyms: Interleukin-3 receptor subunit alpha; IL3R; IL-3RA; IL-3R-alpha; IL-3R subunit alpha; IL-3 receptor subunit alpha; CD123 antigen; CD123
• Gene Name: IL3RA
• DTT Type: Successful target; [1]
• BioChemical Class: Cytokine receptor
• UniProt ID: IL3RA_HUMAN
• TTD ID: T71377
• Sequence:
  MVLLWLTLLLIALPCLLQTKEDPNPPITNLRMKAKAQQLTWDLNRNVTDIECVKDADYSM
  PAVNNSYCQFGAISLCEVTNYTVRVANPPFSTWILFPENSGKPWAGAENLTCWIHDVDFL
  SCSWAVGPGAPADVQYDLYLNVANRRQQYECLHYKTDAQGTRIGCRFDDISRLSSGSQSS
  HILVRGRSAAFGIPCTDKFVVFSQIEILTPPNMTAKCNKTHSFMHWKMRSHFNRKFRYEL
  QIQKRMQPVITEQVRDRTSFQLLNPGTYTVQIRARERVYEFLSAWSTPQRFECDQEEGAN
  TRAWRTSLLIALGTLLALVCVFVICRRYLVMQRLFPRIPHMKDPIGDSFQNDKLVVWEAG
  KAGLEECLVTEVQVVQKT
• Function: This is a receptor for interleukin-3.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  PI3K-Akt signaling pathway (hsa04151)
  Apoptosis (hsa04210)
  Jak-STAT signaling pathway (hsa04630)
  Hematopoietic cell lineage (hsa04640)
• Reactome Pathway:
  G beta (R-HSA-392451)
  Interleukin-3, 5 and GM-CSF signaling (R-HSA-512988)
  RAF/MAP kinase cascade (R-HSA-5673001)
  Interleukin receptor SHC signaling (R-HSA-912526)
  GPVI-mediated activation cascade (R-HSA-114604)

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tagraxofusp	DM9HQ5U	Acute myeloid leukaemia	2A60	Approved	[1]

21 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CD123/CLL1 CAR-T Cells	DM45Z3P	Acute myeloid leukaemia	2A60	Phase 2/3	[2]
Flotetuzumab	DMVR6OM	Acute biphenotypic leukaemia	2B33.4	Phase 2	[3]
MB-102	DMLPNVS	Acute kidney injury	GB60	Phase 2	[3]
Talacotuzumab	DMARVFG	Acute myeloid leukaemia	2A60	Phase 2	[3]
4SCAR19 and 4SCAR123	DMYPQT4	B-cell lymphoma	2A86	Phase 1/2	[4]
Anti-CD123-CAR-transduced T cells	DMFV6TY	leukaemia	2A60-2B33	Phase 1/2	[5]
CART-123 cells	DM0MCTJ	Acute myeloid leukaemia	2A60	Phase 1/2	[6]
CD123-specific gene-engineered T cells	DMHOWU5	Acute myeloid leukaemia	2A60	Phase 1/2	[7]
SAR440234	DM6M8O4	Acute myeloid leukaemia	2A60	Phase 1/2	[8]
Anti-CD123 CAR-T cells	DMYIZFW	leukaemia	2A60-2B33	Phase 1	[9]
Anti-CD123 CAR-T treatment	DM82OS7	N. A.	N. A.	Phase 1	[10]
APVO436	DMUAMZY	Acute myeloid leukaemia	2A60	Phase 1	[11]
CART123 cells	DMD0XWR	Acute myeloid leukaemia	2A60	Phase 1	[12]
CD123-CD33 Ccar	DMUJF9T	Acute myeloid leukaemia	2A60	Phase 1	[13]
CD123CAR-41BB-CD3zeta-EGFRt-expressing T cells	DMDFY1R	Acute myeloid leukaemia	2A60	Phase 1	[14]
CSL-362-AML	DM7I39W	leukaemia	2A60-2B33	Phase 1	[15]
CSL311	DMC21G0	Asthma	CA23	Phase 1	[16]
IM23	DML5O7T	Acute myeloid leukaemia	2A60	Phase 1	[17]
JNJ-63709178	DM5SZAK	Acute myeloid leukaemia	2A60	Phase 1	[18]
MGD006	DMQB4VN	Acute lymphoblastic leukaemia	2A85	Phase 1	[19]
UCART123	DMG7FLI	Acute myeloid leukaemia	2A60	Phase 1	[20]

2 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Autologous Anti-CD 123 CAR TCR/4-1BB-expressing T-lymphocytes	DMYZ3O9	Acute myeloid leukaemia	2A60	Phase 0	[21]
CAR-T cells targeting CD123	DMSZNQE	Acute myeloid leukaemia	2A60	Preclinical	[22]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Daniplestim	DMHJAD4	Osteoporosis	FB83.0	Terminated	[23]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Osteoporosis	FA20	Bone marrow	2.75E-01	-2.73E-03	-0.02
Acute myelocytic leukaemia	2C82	Bone marrow	8.71E-54	0.98	2.64

References

• [1] 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
• [2] ClinicalTrials.gov (NCT03631576) CD123/CLL1 CAR-T Cells for R/R AML
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [4] ClinicalTrials.gov (NCT03125577) Combination CAR-T Cell Therapy Targeting Hematological Malignancies
• [5] ClinicalTrials.gov (NCT02937103) A Clinical Research of CD123-Targeted CAR-T in Myeloid Malignancies
• [6] ClinicalTrials.gov (NCT03291444) CAR-T Cells Combined With Peptide Specific Dendritic Cell in Relapsed/Refractory Leukemia/MDS
• [7] ClinicalTrials.gov (NCT03222674) Multi-CAR T Cell Therapy for Acute Myeloid Leukemia
• [8] Bispecific antibodies: a mechanistic review of the pipeline. Nat Rev Drug Discov. 2019 Aug;18(8):585-608.
• [9] ClinicalTrials.gov (NCT03121625) CAR-T Therapy in Relapsed or Refractory Haematopoietic and Lymphoid Malignancies
• [10] ClinicalTrials.gov (NCT03672851) Study Evaluating Safety and Efficacy of CAR-T Cells Targeting CD123 in Patients With Acute Leukemia
• [11] Clinical pipeline report, company report or official report of Aptevo.
• [12] ClinicalTrials.gov (NCT03766126) Lentivirally Redirected CD123 Autologous T Cells in AML
• [13] Clinical pipeline report, company report or official report of iCell Gene Therapeutics.
• [14] ClinicalTrials.gov (NCT03114670) Donor-derived Anti-CD123-CART Cells for Recurred AML After Allo-HSCT
• [15] Monoclonal antibody targeting of IL-3 receptor alpha with CSL362 effectively depletes CML progenitor and stem cells. Blood. 2014 Feb 20;123(8):1218-28.
• [16] Anti-beta(c) mAb CSL311 inhibits human nasal polyp pathophysiology in a humanized mouse xenograft model. Allergy. 2020 Feb;75(2):475-478.
• [17] ClinicalTrials.gov (NCT03585517) Safety and Efficacy Evaluation of IM23 CAR-T Cells (IM23CAR-T)
• [18] Immune therapies in acute myeloid leukemia: a focus on monoclonal antibodies and immune checkpoint inhibitors. Curr Opin Hematol. 2018 Mar;25(2):136-145.
• [19] A CD3xCD123 bispecific DART for redirecting host T cells to myelogenous leukemia: preclinical activity and safety in nonhuman primates.Sci Transl Med.2015 May 27;7(289):289ra82.
• [20] ClinicalTrials.gov (NCT03190278) Study Evaluating Safety and Efficacy of UCART123 in Patients With Acute Myeloid Leukemia
• [21] ClinicalTrials.gov (NCT02623582) CD123 Redirected Autologous T Cells for AML
• [22] ClinicalTrials.gov (NCT03473457) CAR-T Cells Therapy in Relapsed/Refractory Acute Myeloid Leukemia
• [23] The combined administration of daniplestim and Mpl ligand augments the hematopoietic reconstitution observed with single cytokine administration in a nonhuman primate model of myelosuppression. Stem Cells. 1998;16 Suppl 2:143-54.