Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCAOZP1)

• DOT Name: CDAN1-interacting nuclease 1 (CDIN1)
• Synonyms: Protein HH114
• Gene Name: CDIN1
• Related Disease:
  Congenital dyserythropoietic anemia type type 1B
  Congenital dyserythropoietic anemia type 1
• UniProt ID: CDIN1_HUMAN
• Pfam ID: PF14811
• Sequence:
  MILTKAQYDEIAQCLVSVPPTRQSLRKLKQRFPSQSQATLLSIFSQEYQKHIKRTHAKHH
  TSEAIESYYQRYLNGVVKNGAAPVLLDLANEVDYAPSLMARLILERFLQEHEETPPSKSI
  INSMLRDPSQIPDGVLANQVYQCIVNDCCYGPLVDCIKHAIGHEHEVLLRDLLLEKNLSF
  LDEDQLRAKGYDKTPDFILQVPVAVEGHIIHWIESKASFGDECSHHAYLHDQFWSYWNRF
  GPGLVIYWYGFIQELDCNRERGILLKACFPTNIVTLCHSIA
• Function: Plays a role in erythroid cell differentiation.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Congenital dyserythropoietic anemia type type 1B	DIS1XL7V	Strong	Autosomal recessive	[1]
Congenital dyserythropoietic anemia type 1	DISCBVO6	Supportive	Autosomal recessive	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of CDAN1-interacting nuclease 1 (CDIN1).	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of CDAN1-interacting nuclease 1 (CDIN1).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of CDAN1-interacting nuclease 1 (CDIN1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of CDAN1-interacting nuclease 1 (CDIN1).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of CDAN1-interacting nuclease 1 (CDIN1).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of CDAN1-interacting nuclease 1 (CDIN1).	[7]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of CDAN1-interacting nuclease 1 (CDIN1).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of CDAN1-interacting nuclease 1 (CDIN1).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of CDAN1-interacting nuclease 1 (CDIN1).	[10]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID increases the expression of CDAN1-interacting nuclease 1 (CDIN1).	[11]

References

• [1] Homozygous mutations in a predicted endonuclease are a novel cause of congenital dyserythropoietic anemia type I. Haematologica. 2013 Sep;98(9):1383-7. doi: 10.3324/haematol.2013.089490. Epub 2013 May 28.
• [2] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [5] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [8] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [9] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [10] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [11] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.