Details of the Drug Therapeutic Target (DTT)

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

• DTT Name: Cyclic ADP-ribose hydrolase 1 (CD38)
• Synonyms: cADPr hydrolase 1; T10; Cyclic ADPribose hydrolase 1; ADPribosyl cyclase 1; ADPRC 1; ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1; ADP-ribosyl cyclase 1; 2'-phospho-cyclic-ADP-ribose transferase; 2'-phospho-ADP-ribosyl cyclase/2'-phospho-cyclic-ADP-ribose transferase; 2'-phospho-ADP-ribosyl cyclase
• Gene Name: CD38
• DTT Type: Successful target; [1]
• BioChemical Class: Glycosylase
• UniProt ID: CD38_HUMAN
• TTD ID: T10877
• EC Number: EC 3.2.2.6
• Sequence:
  MANCEFSPVSGDKPCCRLSRRAQLCLGVSILVLILVVVLAVVVPRWRQQWSGPGTTKRFP
  ETVLARCVKYTEIHPEMRHVDCQSVWDAFKGAFISKHPCNITEEDYQPLMKLGTQTVPCN
  KILLWSRIKDLAHQFTQVQRDMFTLEDTLLGYLADDLTWCGEFNTSKINYQSCPDWRKDC
  SNNPVSVFWKTVSRRFAEAACDVVHVMLNGSRSKIFDKNSTFGSVEVHNLQPEKVQTLEA
  WVIHGGREDSRDLCQDPTIKELESIISKRNIQFSCKNIYRPDKFLQCVKNPEDSSCTSEI
• Function: Has cADPr hydrolase activity. Also moonlights as a receptor in cells of the immune system. Synthesizes the second messagers cyclic ADP-ribose and nicotinate-adenine dinucleotide phosphate, the former a second messenger for glucose-induced insulin secretion.
• KEGG Pathway:
  Nicotinate and nicotinamide metabolism (hsa00760)
  Metabolic pathways (hsa01100)
  Calcium signaling pathway (hsa04020)
  Hematopoietic cell lineage (hsa04640)
  Oxytocin signaling pathway (hsa04921)
  Salivary secretion (hsa04970)
  Pancreatic secretion (hsa04972)
  Epstein-Barr virus infection (hsa05169)
• Reactome Pathway: Nicotinate metabolism (R-HSA-196807)
• BioCyc Pathway: MetaCyc:HS00103-MON

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Daratumumab	DMKCIUZ	Multiple myeloma	2A83	Approved	[1]

21 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Mezagitamab	DMWJXFO	Myasthenia gravis	8C6Y	Phase 2	[2]
4SCAR19 and 4SCAR38	DMZKFU7	B-cell lymphoma	2A86	Phase 1/2	[3]
Anti-CD38 CAR-T cells	DMTVXBY	Multiple myeloma	2A83	Phase 1/2	[4]
CD38 and BCMA CAR-T Cells	DMFZS8A	Multiple myeloma	2A83	Phase 1/2	[5]
CD38 CAR T cells	DMPS3I6	Multiple myeloma	2A83	Phase 1/2	[6]
CD38 CAR-T Cell	DM0USBX	Acute lymphoblastic leukaemia	2A85	Phase 1/2	[7]
CD38-specific gene-engineered T cells	DMCH98G	Acute myeloid leukaemia	2A60	Phase 1/2	[8]
ISB 1342	DMG107N	Multiple myeloma	2A83	Phase 1/2	[9]
MOR-202	DMR8AHJ	Multiple myeloma	2A83	Phase 1/2	[10]
SAR-650984	DMD20YH	Haematological malignancy	2B33.Y	Phase 1/2	[11]
225Ac-labelled aCD38	DM3E2IY	Multiple myeloma	2A83	Phase 1	[12]
AMG 424	DMLAP8F	Multiple myeloma	2A83	Phase 1	[13]
CART-38 cells	DMKN8XD	Acute myeloid leukaemia	2A60	Phase 1	[14]
CD38 CAR-T	DMNX0V7	Multiple myeloma	2A83	Phase 1	[15]
KP1237	DMCGY7Q	Multiple myeloma	2A83	Phase 1	[16]
SAR442085	DM5UXAB	Plasma cell myeloma	2A83.1	Phase 1	[17]
SAR442257	DMXD5QP	Malignant neoplasm	2A00-2F9Z	Phase 1	[17]
SAR444559	DM4OMYQ	Inflammation	1A00-CA43.1	Phase 1	[18]
TAK-169	DMRINBJ	Multiple myeloma	2A83	Phase 1	[19]
TAK-573	DMUXAP1	Multiple myeloma	2A83	Phase 1	[20]
CAR-T cells targeting CD38	DMH5C37	Multiple myeloma	2A83	Clinical trial	[21]

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
HuMax-CD38b	DM4FIZJ	Solid tumour/cancer	2A00-2F9Z	Investigative	[22]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Multiple myeloma	2C82	Bone marrow	8.33E-02	0.22	0.69

The Drug-Metabolizing Enzyme (DME) Role of This DTT

• DTT DME Name: Cyclic ADP-ribose hydrolase 1 (CD38) DME Info
• Gene Name: CD38

1 Approved Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Vitamin B3	DMQVRZH	Chronic renal failure	GB61.Z	Approved	[23]

References

• [1] Targeting CD38 with Daratumumab Monotherapy in Multiple Myeloma. N Engl J Med. 2015 Sep 24;373(13):1207-19.
• [2] Safety, tolerability, pharmacokinetics and pharmacodynamics of the anti-CD38 cytolytic antibody TAK-079 in healthy subjects. Br J Clin Pharmacol. 2020 Jul;86(7):1314-1325.
• [3] ClinicalTrials.gov (NCT03125577) Combination CAR-T Cell Therapy Targeting Hematological Malignancies
• [4] ClinicalTrials.gov (NCT03464916) Study to Evaluate the Safety and Efficacy of Anti-CD38 CAR-T in Relapsed or Refractory Multiple Myeloma Patients
• [5] ClinicalTrials.gov (NCT03767751) A Feasibility and Safety Study of Dual Specificity CD38 and BCMA CAR-T Cell Immunotherapy for Relapsed or Refractory Multiple Myeloma
• [6] ClinicalTrials.gov (NCT03271632) Multi-CAR T Cell Therapy in the Treatment of Multiple Myeloma
• [7] ClinicalTrials.gov (NCT03754764) A Feasibility and Safety Study of CD38 CAR-T Cell Immunotherapy for Relapsed B-cell Acute Lymphoblastic Leukemia After CD19 CAR-T Adoptive Cellular Immunotherapy
• [8] ClinicalTrials.gov (NCT03222674) Multi-CAR T Cell Therapy for Acute Myeloid Leukemia
• [9] Clinical pipeline report, company report or official report of Ichnos Sciences.
• [10] Clinical pipeline report, company report or official report of MorphoSys.
• [11] Clinical pipeline report, company report or official report of Sanofi-Aventis.
• [12] Radiopharmaceutical therapy in cancer: clinical advances and challenges. Nat Rev Drug Discov. 2020 Sep;19(9):589-608.
• [13] Clinical pipeline report, company report or official report of Amgen.
• [14] ClinicalTrials.gov (NCT03291444) CAR-T Cells Combined With Peptide Specific Dendritic Cell in Relapsed/Refractory Leukemia/MDS
• [15] Clinical pipeline report, company report or official report of Sorrento Therapeutics.
• [16] ClinicalTrials.gov (NCT04634435) A Phase 1 Study of Autologous Memory-like Natural Killer (NK) Cell Immunotherapy With BHV-1100 (Formerly KP1237) and IVIG Followed by Low Dose IL-2 as Early Post-Autologous Transplant Consolidation in Minimal Residual Disease Positive, Multiple Myeloma (MM) Patients in First or Second Remission. U.S.National Institutes of Health.
• [17] Clinical pipeline report, company report or official report of Sanofi.
• [18] Clinical pipeline report, company report or official report of Sanofi
• [19] Clinical pipeline report, company report or official report of Molecular Templates.
• [20] Clinical pipeline report, company report or official report of Takeda.
• [21] ClinicalTrials.gov (NCT03473457) CAR-T Cells Therapy in Relapsed/Refractory Acute Myeloid Leukemia
• [22] 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: 2766).
• [23] ADP-ribosyl cyclase and CD38 catalyze the synthesis of a calcium-mobilizing metabolite from NADP. J Biol Chem. 1995 Dec 22;270(51):30327-33.