Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTPW9LJ)

• DTT Name: Co-stimulatory molecule 4-1BB (CD137)
• Synonyms: Tumor necrosis factor receptor superfamily member 9; T-cell antigen ILA; T-cell antigen 4-1BB homolog; ILA; CDw137; 4-1BB ligand receptor
• Gene Name: TNFRSF9
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Cytokine receptor
• UniProt ID: TNR9_HUMAN
• TTD ID: T93923
• Sequence:
  MGNSCYNIVATLLLVLNFERTRSLQDPCSNCPAGTFCDNNRNQICSPCPPNSFSSAGGQR
  TCDICRQCKGVFRTRKECSSTSNAECDCTPGFHCLGAGCSMCEQDCKQGQELTKKGCKDC
  CFGTFNDQKRGICRPWTNCSLDGKSVLVNGTKERDVVCGPSPADLSPGASSVTPPAPARE
  PGHSPQIISFFLALTSTALLFLLFFLTLRFSVVKRGRKKLLYIFKQPFMRPVQTTQEEDG
  CSCRFPEEEEGGCEL
• Function: Possibly active during T cell activation. Receptor for TNFSF9/4-1BBL.
• KEGG Pathway: Cytokine-cytokine receptor interaction (hsa04060)
• Reactome Pathway: TNFs bind their physiological receptors (R-HSA-5669034)

Molecular Interaction Atlas (MIA) of This DTT

20 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Anti-CD137	DMHVZ27	Solid tumour/cancer	2A00-2F9Z	Phase 2	[1]
Urelumab	DM6RTVG	B-cell non-hodgkin lymphoma	2B33.5	Phase 2	[2]
ADG106	DM87H0S	Non-hodgkin lymphoma	2B33.5	Phase 1/2	[3]
CD137 CAR-T Cell	DMHMC19	Acute lymphoblastic leukaemia	2A85	Phase 1/2	[4]
MG7-CART	DME6PB0	Acute myeloid leukaemia	2A60	Phase 1/2	[5]
NM21-1480	DMDNJP5	Advanced solid tumour	2A00-2F9Z	Phase 1/2	[6]
AGEN2373	DMAXVZ1	Solid tumour/cancer	2A00-2F9Z	Phase 1	[7]
AMG 506	DMG64PE	Solid tumour/cancer	2A00-2F9Z	Phase 1	[8]
CD28 and CD137 CAR-T Cells	DMFGQXB	Acute lymphoblastic leukaemia	2A85	Phase 1	[9]
CTX-471	DMMPKN3	Solid tumour/cancer	2A00-2F9Z	Phase 1	[10]
GEN1042	DMNP6T3	Solid tumour/cancer	2A00-2F9Z	Phase 1	[11]
GEN1046	DMEWRNZ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[11]
INBRX-105	DM2FH10	Solid tumour/cancer	2A00-2F9Z	Phase 1	[12]
LVGN6051	DMPQE2S	Solid tumour/cancer	2A00-2F9Z	Phase 1	[13]
MCLA-145	DM8CGUV	Lymphoma	2A80-2A86	Phase 1	[14]
PF-05082566	DMAEK3L	Non-hodgkin lymphoma	2B33.5	Phase 1	[15]
RG6076	DMO9BGI	Hematologic tumour	2B33.Y	Phase 1	[16]
RG6524	DMT22UV	Aggressive cancer	2A00-2F9Z	Phase 1	[17]
RG7827	DMRGHKN	Solid tumour/cancer	2A00-2F9Z	Phase 1	[16]
Utomilumab	DMIKV9W	Solid tumour/cancer	2A00-2F9Z	Phase 1	[18]

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
HG-1051	DMM4JCA	Immune System disease	4A01-4B41	Investigative	[1]

References

• [1] 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: 1878).
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] Clinical pipeline report, company report or official report of Adagene.
• [4] ClinicalTrials.gov (NCT02965092) CD19 Chimeric Antigen Receptor (CAR)-Modified T Cell Therapy in Treating Patients With B-cell Malignancies
• [5] ClinicalTrials.gov (NCT02862704) A Study of MG7 Redirected Autologous T Cells for Advanced MG7 Positive Liver Metastases(MG7-CART)
• [6] Clinical pipeline report, company report or official report of Numab Therapeutics.
• [7] Clinical pipeline report, company report or official report of Agenus.
• [8] Clinical pipeline report, company report or official report of Amgen.
• [9] ClinicalTrials.gov (NCT02186860) Chimeric Antigen Receptor (CAR)-Modified T Cell Therapy in Treating Patients With Acute Lymphoblastic Leukemia
• [10] Clinical pipeline report, company report or official report of Compass Therapeutics.
• [11] Clinical pipeline report, company report or official report of Genmab.
• [12] Clinical pipeline report, company report or official report of Inhibrx.
• [13] Optimization of 4-1BB antibody for cancer immunotherapy by balancing agonistic strength with FcR affinity. Nat Commun. 2019 May 20;10(1):2141.
• [14] Clinical pipeline report, company report or official report of Merus.
• [15] Targeting of 4-1BB by monoclonal antibody PF-05082566 enhances T-cell function and promotes anti-tumor activity. Cancer Immunol Immunother. 2012 Oct;61(10):1721-33.
• [16] Clinical pipeline report, company report or official report of Roche.
• [17] Clinical pipeline report, company report or official report of Roche
• [18] First-in-Human Study of Utomilumab, a 4-1BB/CD137 Agonist, in Combination with Rituximab in Patients with Follicular and Other CD20 + Non-Hodgkin Lymphomas. Clin Cancer Res. 2020 Jun 1;26(11):2524-2534.