Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJIJ5AL)

• DOT Name: cAMP-responsive element modulator (CREM)
• Synonyms: Inducible cAMP early repressor; ICER
• Gene Name: CREM
• Related Disease:
  Allergic contact dermatitis
  Atrial fibrillation
  Inflammatory bowel disease
  Autoimmune disease
  Carcinoma
  Cardiac failure
  Cervical cancer
  Cervical carcinoma
  Colon cancer
  Colon carcinoma
  Congestive heart failure
  Diabetic kidney disease
  Esophageal squamous cell carcinoma
  Hyperglycemia
  Influenza
  Juvenile idiopathic arthritis
  Lupus
  Male infertility
  Mental disorder
  Metastatic malignant neoplasm
  Obesity
  Prostate cancer
  Prostate carcinoma
  Prostate neoplasm
  Melanoma
  Neuroblastoma
  Panic disorder
  Breast cancer
  Breast carcinoma
  Pancreatic cancer
  Adenocarcinoma
  Ankylosing spondylitis
  Anxiety disorder
  Cardiomyopathy
  Cardiovascular disease
  Clear cell sarcoma
  Crohn disease
  Hepatitis C virus infection
  Myocardial infarction
  Non-insulin dependent diabetes
  Psoriasis
  Sclerosing cholangitis
  Systemic lupus erythematosus
  Type-1/2 diabetes
  Ulcerative colitis
• UniProt ID: CREM_HUMAN
• Pfam ID: PF00170 ; PF02173
• Sequence:
  MTMETVESQHDGSITASLTESKSAHVQTQTGQNSIPALAQVSVAGSGTRRGSPAVTLVQL
  PSGQTIHVQGVIQTPQPWVIQSSEIHTVQVAAIAETDESAESEGVIDSHKRREILSRRPS
  YRKILNELSSDVPGVPKIEEERSEEEGTPPSIATMAVPTSIYQTSTGQYIAIAQGGTIQI
  SNPGSDGVQGLQALTMTNSGAPPPGATIVQYAAQSADGTQQFFVPGSQVVVQDEETELAP
  SHMAAATGDMPTYQIRAPTAALPQGVVMAASPGSLHSPQQLAEEATRKRELRLMKNREAA
  KECRRRKKEYVKCLESRVAVLEVQNKKLIEELETLKDICSPKTDY
• Function: Transcriptional regulator that binds the cAMP response element (CRE), a sequence present in many viral and cellular promoters. Isoforms are either transcriptional activators or repressors. Plays a role in spermatogenesis and is involved in spermatid maturation ; [Isoform 6]: May play a role in the regulation of the circadian clock: acts as a transcriptional repressor of the core circadian component PER1 by directly binding to cAMP response elements in its promoter.
• Tissue Specificity: Expressed in testes (round spermatids) (at protein level). Isoform 14 is the major activator form in testes.
• KEGG Pathway: Adrenergic sig.ling in cardiomyocytes (hsa04261)

Molecular Interaction Atlas (MIA) of This DOT

45 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Allergic contact dermatitis	DISFFVF9	Definitive	Biomarker	[1]
Atrial fibrillation	DIS15W6U	Definitive	Altered Expression	[2]
Inflammatory bowel disease	DISGN23E	Definitive	Biomarker	[3]
Autoimmune disease	DISORMTM	Strong	Biomarker	[4]
Carcinoma	DISH9F1N	Strong	Biomarker	[5]
Cardiac failure	DISDC067	Strong	Biomarker	[6]
Cervical cancer	DISFSHPF	Strong	Genetic Variation	[7]
Cervical carcinoma	DIST4S00	Strong	Genetic Variation	[7]
Colon cancer	DISVC52G	Strong	Biomarker	[8]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[8]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[6]
Diabetic kidney disease	DISJMWEY	Strong	Altered Expression	[9]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[10]
Hyperglycemia	DIS0BZB5	Strong	Altered Expression	[11]
Influenza	DIS3PNU3	Strong	Biomarker	[12]
Juvenile idiopathic arthritis	DISQZGBV	Strong	Biomarker	[13]
Lupus	DISOKJWA	Strong	Biomarker	[14]
Male infertility	DISY3YZZ	Strong	Genetic Variation	[15]
Mental disorder	DIS3J5R8	Strong	Biomarker	[16]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[10]
Obesity	DIS47Y1K	Strong	Altered Expression	[17]
Prostate cancer	DISF190Y	Strong	Altered Expression	[18]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[18]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[18]
Melanoma	DIS1RRCY	moderate	Altered Expression	[19]
Neuroblastoma	DISVZBI4	moderate	Biomarker	[20]
Panic disorder	DISD3VNY	moderate	Genetic Variation	[21]
Breast cancer	DIS7DPX1	Disputed	Biomarker	[22]
Breast carcinoma	DIS2UE88	Disputed	Biomarker	[22]
Pancreatic cancer	DISJC981	Disputed	Biomarker	[22]
Adenocarcinoma	DIS3IHTY	Limited	Altered Expression	[23]
Ankylosing spondylitis	DISRC6IR	Limited	Genetic Variation	[24]
Anxiety disorder	DISBI2BT	Limited	Biomarker	[25]
Cardiomyopathy	DISUPZRG	Limited	Biomarker	[26]
Cardiovascular disease	DIS2IQDX	Limited	Biomarker	[27]
Clear cell sarcoma	DIS1MTE6	Limited	Biomarker	[5]
Crohn disease	DIS2C5Q8	Limited	Genetic Variation	[28]
Hepatitis C virus infection	DISQ0M8R	Limited	Biomarker	[29]
Myocardial infarction	DIS655KI	Limited	Biomarker	[30]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Altered Expression	[31]
Psoriasis	DIS59VMN	Limited	Genetic Variation	[24]
Sclerosing cholangitis	DIS7GZNB	Limited	Genetic Variation	[24]
Systemic lupus erythematosus	DISI1SZ7	Limited	Altered Expression	[14]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[32]
Ulcerative colitis	DIS8K27O	Limited	Genetic Variation	[24]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Etoposide	DMNH3PG	Approved	cAMP-responsive element modulator (CREM) affects the response to substance of Etoposide.	[56]

4 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 cAMP-responsive element modulator (CREM).	[33]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of cAMP-responsive element modulator (CREM).	[47]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of cAMP-responsive element modulator (CREM).	[49]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of cAMP-responsive element modulator (CREM).	[51]

20 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 cAMP-responsive element modulator (CREM).	[34]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of cAMP-responsive element modulator (CREM).	[35]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of cAMP-responsive element modulator (CREM).	[36]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of cAMP-responsive element modulator (CREM).	[37]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of cAMP-responsive element modulator (CREM).	[38]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of cAMP-responsive element modulator (CREM).	[39]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of cAMP-responsive element modulator (CREM).	[40]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of cAMP-responsive element modulator (CREM).	[41]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of cAMP-responsive element modulator (CREM).	[42]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of cAMP-responsive element modulator (CREM).	[43]
Azacitidine	DMTA5OE	Approved	Azacitidine decreases the expression of cAMP-responsive element modulator (CREM).	[44]
Rigosertib	DMOSTXF	Phase 3	Rigosertib increases the expression of cAMP-responsive element modulator (CREM).	[45]
DNCB	DMDTVYC	Phase 2	DNCB increases the expression of cAMP-responsive element modulator (CREM).	[1]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of cAMP-responsive element modulator (CREM).	[48]
Eugenol	DM7US1H	Patented	Eugenol increases the expression of cAMP-responsive element modulator (CREM).	[1]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of cAMP-responsive element modulator (CREM).	[50]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of cAMP-responsive element modulator (CREM).	[52]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of cAMP-responsive element modulator (CREM).	[53]
cinnamaldehyde	DMZDUXG	Investigative	cinnamaldehyde increases the expression of cAMP-responsive element modulator (CREM).	[54]
NSC-1771	DMNXDGQ	Investigative	NSC-1771 increases the expression of cAMP-responsive element modulator (CREM).	[55]

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