Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXYX5JH)

• DOT Name: Chromogranin-A (CHGA)
• Synonyms: CgA; Pituitary secretory protein I; SP-I
• Gene Name: CHGA
• Related Disease:
  Chronic renal failure
  Colitis
  End-stage renal disease
  Non-insulin dependent diabetes
  Pancreatic neuroendocrine tumor
  Advanced cancer
  Alzheimer disease
  Amyotrophic lateral sclerosis
  Arteriosclerosis
  Atherosclerosis
  Castration-resistant prostate carcinoma
  Colorectal carcinoma
  Essential hypertension
  Gastrin-producing neuroendocrine tumor
  High blood pressure
  Lung neoplasm
  Metabolic disorder
  Non-small-cell lung cancer
  Obesity
  Obstructive sleep apnea
  Paraganglioma
  Pheochromocytoma
  Primitive neuroectodermal tumor
  Prostate neoplasm
  Small-cell lung cancer
  Squamous cell carcinoma
  Type-1 diabetes
  Type-1/2 diabetes
  Ulcerative colitis
  Neuralgia
  Schizophrenia
  Acute coronary syndrome
  Acute myelogenous leukaemia
  Adenocarcinoma
  Atopic dermatitis
  Breast carcinoma
  Carcinoma
  Cardiac failure
  Chronic kidney disease
  Congestive heart failure
  Coronary heart disease
  Inflammatory bowel disease
  Medullary thyroid gland carcinoma
  Neuroblastoma
  Neuroendocrine cancer
  Von hippel-lindau disease
• UniProt ID: CMGA_HUMAN
• PDB ID: 1LV4; 6R2X
• Pfam ID: PF01271
• Sequence:
  MRSAAVLALLLCAGQVTALPVNSPMNKGDTEVMKCIVEVISDTLSKPSPMPVSQECFETL
  RGDERILSILRHQNLLKELQDLALQGAKERAHQQKKHSGFEDELSEVLENQSSQAELKEA
  VEEPSSKDVMEKREDSKEAEKSGEATDGARPQALPEPMQESKAEGNNQAPGEEEEEEEEA
  TNTHPPASLPSQKYPGPQAEGDSEGLSQGLVDREKGLSAEPGWQAKREEEEEEEEEAEAG
  EEAVPEEEGPTVVLNPHPSLGYKEIRKGESRSEALAVDGAGKPGAEEAQDPEGKGEQEHS
  QQKEEEEEMAVVPQGLFRGGKSGELEQEEERLSKEWEDSKRWSKMDQLAKELTAEKRLEG
  QEEEEDNRDSSMKLSFRARAYGFRGPGPQLRRGWRPSSREDSLEAGLPLQVRGYPEEKKE
  EEGSANRRPEDQELESLSAIEAELEKVAHQLQALRRG
• Function: [Pancreastatin]: Strongly inhibits glucose induced insulin release from the pancreas.; [Catestatin]: Inhibits catecholamine release from chromaffin cells and noradrenergic neurons by acting as a non-competitive nicotinic cholinergic antagonist. Displays antibacterial activity against Gram-positive bacteria S.aureus and M.luteus, and Gram-negative bacteria E.coli and P.aeruginosa. Can induce mast cell migration, degranulation and production of cytokines and chemokines. Acts as a potent scavenger of free radicals in vitro. May play a role in the regulation of cardiac function and blood pressure ; [Serpinin]: Regulates granule biogenesis in endocrine cells by up-regulating the transcription of protease nexin 1 (SERPINE2) via a cAMP-PKA-SP1 pathway. This leads to inhibition of granule protein degradation in the Golgi complex which in turn promotes granule formation.
• Tissue Specificity: Detected in cerebrospinal fluid (at protein level) . Detected in urine (at protein level) .; [GE-25]: Found in the brain.
• Reactome Pathway: Antimicrobial peptides (R-HSA-6803157)

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chronic renal failure	DISGG7K6	Definitive	Biomarker	[1]
Colitis	DISAF7DD	Definitive	Biomarker	[2]
End-stage renal disease	DISXA7GG	Definitive	Biomarker	[1]
Non-insulin dependent diabetes	DISK1O5Z	Definitive	Biomarker	[3]
Pancreatic neuroendocrine tumor	DISDMPU0	Definitive	Biomarker	[4]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[5]
Alzheimer disease	DISF8S70	Strong	Biomarker	[6]
Amyotrophic lateral sclerosis	DISF7HVM	Strong	Biomarker	[7]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[8]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[8]
Castration-resistant prostate carcinoma	DISVGAE6	Strong	Biomarker	[9]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[10]
Essential hypertension	DIS7WI98	Strong	Biomarker	[11]
Gastrin-producing neuroendocrine tumor	DIS8TYKO	Strong	Biomarker	[12]
High blood pressure	DISY2OHH	Strong	Biomarker	[13]
Lung neoplasm	DISVARNB	Strong	Altered Expression	[14]
Metabolic disorder	DIS71G5H	Strong	Genetic Variation	[15]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[16]
Obesity	DIS47Y1K	Strong	Biomarker	[17]
Obstructive sleep apnea	DIS0SVD1	Strong	Biomarker	[18]
Paraganglioma	DIS2XXH5	Strong	Biomarker	[19]
Pheochromocytoma	DIS56IFV	Strong	Biomarker	[20]
Primitive neuroectodermal tumor	DISFHXHA	Strong	Biomarker	[21]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[22]
Small-cell lung cancer	DISK3LZD	Strong	Biomarker	[23]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[24]
Type-1 diabetes	DIS7HLUB	Strong	Biomarker	[25]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[3]
Ulcerative colitis	DIS8K27O	Strong	Biomarker	[26]
Neuralgia	DISWO58J	moderate	Biomarker	[27]
Schizophrenia	DISSRV2N	moderate	Genetic Variation	[28]
Acute coronary syndrome	DIS7DYEW	Limited	Biomarker	[29]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[30]
Adenocarcinoma	DIS3IHTY	Limited	Altered Expression	[24]
Atopic dermatitis	DISTCP41	Limited	Altered Expression	[31]
Breast carcinoma	DIS2UE88	Limited	Genetic Variation	[32]
Carcinoma	DISH9F1N	Limited	Biomarker	[33]
Cardiac failure	DISDC067	Limited	Biomarker	[11]
Chronic kidney disease	DISW82R7	Limited	Biomarker	[34]
Congestive heart failure	DIS32MEA	Limited	Biomarker	[11]
Coronary heart disease	DIS5OIP1	Limited	Altered Expression	[29]
Inflammatory bowel disease	DISGN23E	Limited	Biomarker	[35]
Medullary thyroid gland carcinoma	DISHBL3K	Limited	Altered Expression	[36]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[37]
Neuroendocrine cancer	DISVGJET	Limited	Biomarker	[38]
Von hippel-lindau disease	DIS6ZFQQ	Limited	Biomarker	[39]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Chromogranin-A (CHGA).	[40]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Chromogranin-A (CHGA).	[41]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Chromogranin-A (CHGA).	[42]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Chromogranin-A (CHGA).	[43]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Chromogranin-A (CHGA).	[44]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Chromogranin-A (CHGA).	[45]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol affects the expression of Chromogranin-A (CHGA).	[46]
Azacitidine	DMTA5OE	Approved	Azacitidine decreases the expression of Chromogranin-A (CHGA).	[47]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Chromogranin-A (CHGA).	[45]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Chromogranin-A (CHGA).	[48]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Chromogranin-A (CHGA).	[49]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Chromogranin-A (CHGA).	[45]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Chromogranin-A (CHGA).	[51]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Chromogranin-A (CHGA).	[46]

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 Chromogranin-A (CHGA).	[50]

References

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