Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTG0TTX7)

• DOT Name: ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 (CD38)
• Synonyms: EC 3.2.2.-; EC 3.2.2.6; 2'-phospho-ADP-ribosyl cyclase; 2'-phospho-ADP-ribosyl cyclase/2'-phospho-cyclic-ADP-ribose transferase; EC 2.4.99.20; 2'-phospho-cyclic-ADP-ribose transferase; ADP-ribosyl cyclase 1; ADPRC 1; Cyclic ADP-ribose hydrolase 1; cADPR hydrolase 1; T10; CD antigen CD38
• Gene Name: CD38
• UniProt ID: CD38_HUMAN
• PDB ID: 1YH3 ; 1ZVM ; 2EF1 ; 2HCT ; 2I65 ; 2I66 ; 2I67 ; 2O3Q ; 2O3R ; 2O3S ; 2O3T ; 2O3U ; 2PGJ ; 2PGL ; 3DZF ; 3DZG ; 3DZH ; 3DZI ; 3DZJ ; 3DZK ; 3F6Y ; 3I9M ; 3I9N ; 3OFS ; 3RAJ ; 3ROK ; 3ROM ; 3ROP ; 3ROQ ; 3U4H ; 3U4I ; 4CMH ; 4F45 ; 4F46 ; 4OGW ; 4TMF ; 4XJS ; 4XJT ; 5F1K ; 5F1O ; 5F21 ; 6EDR ; 6VUA ; 7DHA ; 7DUO ; 7VKE ; 8BYU ; 8D0M ; 8IL3 ; 8P8C
• EC Number: 2.4.99.20; 3.2.2.-; 3.2.2.6
• Pfam ID: PF02267
• Sequence:
  MANCEFSPVSGDKPCCRLSRRAQLCLGVSILVLILVVVLAVVVPRWRQQWSGPGTTKRFP
  ETVLARCVKYTEIHPEMRHVDCQSVWDAFKGAFISKHPCNITEEDYQPLMKLGTQTVPCN
  KILLWSRIKDLAHQFTQVQRDMFTLEDTLLGYLADDLTWCGEFNTSKINYQSCPDWRKDC
  SNNPVSVFWKTVSRRFAEAACDVVHVMLNGSRSKIFDKNSTFGSVEVHNLQPEKVQTLEA
  WVIHGGREDSRDLCQDPTIKELESIISKRNIQFSCKNIYRPDKFLQCVKNPEDSSCTSEI
• Function: Synthesizes cyclic ADP-ribose (cADPR), a second messenger for glucose-induced insulin secretion. Synthesizes the Ca(2+) mobilizer nicotinate-adenine dinucleotide phosphate, NAADP(+), from 2'-phospho-cADPR and nicotinic acid, as well as from NADP(+) and nicotinic acid. At both pH 5.0 and pH 7.4 preferentially transforms 2'-phospho-cADPR into NAADP(+), while preferentially cleaving NADP(+) to cADPR and ADPRP rather than into NADDP(+). Has cADPR hydrolase activity.
• Tissue Specificity: Expressed at high levels in pancreas, liver, kidney, brain, testis, ovary, placenta, malignant lymphoma and neuroblastoma.
• KEGG Pathway:
  Nicoti.te and nicoti.mide metabolism (hsa00760)
  Metabolic pathways (hsa01100)
  Calcium sig.ling pathway (hsa04020)
  Hematopoietic cell lineage (hsa04640)
  Oxytocin sig.ling pathway (hsa04921)
  Salivary secretion (hsa04970)
  Pancreatic secretion (hsa04972)
• Reactome Pathway: Nicotinate metabolism (R-HSA-196807)
• BioCyc Pathway: MetaCyc:HS00103-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

18 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 (CD38).	[1]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 (CD38).	[2]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 (CD38).	[3]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 (CD38).	[4]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 (CD38).	[5]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil affects the expression of ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 (CD38).	[6]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 (CD38).	[7]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 (CD38).	[8]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 (CD38).	[9]
Alitretinoin	DMME8LH	Approved	Alitretinoin increases the expression of ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 (CD38).	[10]
Omacetaxine mepesuccinate	DMPU2WX	Approved	Omacetaxine mepesuccinate increases the expression of ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 (CD38).	[3]
Novobiocin	DMRFWGK	Approved	Novobiocin increases the expression of ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 (CD38).	[11]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 (CD38).	[12]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 (CD38).	[1]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 (CD38).	[14]
PMID27336223-Compound-5	DM6E50A	Patented	PMID27336223-Compound-5 increases the expression of ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 (CD38).	[4]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN decreases the expression of ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 (CD38).	[15]
ISONICOTINIC ACID	DMUVAIF	Investigative	ISONICOTINIC ACID increases the expression of ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 (CD38).	[17]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 (CD38).	[13]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Fmet-leu-phe	DMQ391A	Investigative	Fmet-leu-phe increases the cleavage of ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 (CD38).	[16]

References

• [1] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [2] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [3] Synergistic killing effects of homoharringtonine and arsenic trioxide on acute myeloid leukemia stem cells and the underlying mechanisms. J Exp Clin Cancer Res. 2019 Jul 15;38(1):308. doi: 10.1186/s13046-019-1295-8.
• [4] Retinoic acid-induced CD38 expression in HL-60 myeloblastic leukemia cells regulates cell differentiation or viability depending on expression levels. J Cell Biochem. 2006 Apr 15;97(6):1328-38. doi: 10.1002/jcb.20745.
• [5] Progesterone promotes differentiation of human cord blood fetal T cells into T regulatory cells but suppresses their differentiation into Th17 cells. J Immunol. 2011 Aug 15;187(4):1778-87. doi: 10.4049/jimmunol.1003919. Epub 2011 Jul 18.
• [6] Multi-level gene expression profiles affected by thymidylate synthase and 5-fluorouracil in colon cancer. BMC Genomics. 2006 Apr 3;7:68. doi: 10.1186/1471-2164-7-68.
• [7] All-trans-retinoic acid accelerates the differentiation of human B lymphocytes maturing into plasma cells. Int Immunopharmacol. 2005 Dec;5(13-14):1830-8. doi: 10.1016/j.intimp.2005.06.002. Epub 2005 Jun 21.
• [8] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [9] Dasatinib, a small-molecule protein tyrosine kinase inhibitor, inhibits T-cell activation and proliferation. Blood. 2008 Feb 1;111(3):1366-77. doi: 10.1182/blood-2007-04-084814. Epub 2007 Oct 25.
• [10] Arginine methylation provides epigenetic transcription memory for retinoid-induced differentiation in myeloid cells. Mol Cell Biol. 2005 Jul;25(13):5648-63.
• [11] Novobiocin is a novel inducer of CD38 on cells of the myelomonocytic lineage. Biochim Biophys Acta. 2002 Jan 30;1542(1-3):32-40. doi: 10.1016/s0167-4889(01)00163-x.
• [12] Molecular mechanisms of resveratrol action in lung cancer cells using dual protein and microarray analyses. Cancer Res. 2007 Dec 15;67(24):12007-17. doi: 10.1158/0008-5472.CAN-07-2464.
• [13] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [14] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [15] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.
• [16] CD38 cleavage in fMLP- and IL-8-induced chemotaxis is dependent on p38 MAP kinase but independent of p44/42 MAP kinase. Cell Signal. 2005 Feb;17(2):167-75. doi: 10.1016/j.cellsig.2004.06.008.
• [17] Expression of CD38 in human promyelocytic leukemia HL-60 cell line during differentiation by niacin-related compounds. Biosci Biotechnol Biochem. 2003 Aug;67(8):1836-9. doi: 10.1271/bbb.67.1836.