Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTK1YLWQ)

• DOT Name: Osteocalcin (BGLAP)
• Synonyms: Bone Gla protein; BGP; Gamma-carboxyglutamic acid-containing protein
• Gene Name: BGLAP
• Related Disease:
  Osteogenesis imperfecta
  Arteriosclerosis
  Asthma
  Atherosclerosis
  Bone disease
  Breast cancer
  Breast carcinoma
  Chronic renal failure
  Congenital hypothyroidism
  Congestive heart failure
  Coronary heart disease
  Crohn disease
  Cushing disease
  Dilated cardiomyopathy 1A
  End-stage renal disease
  High blood pressure
  Hypercalcaemia
  Hyperglycemia
  Hyperinsulinemia
  Hyperthyroidism
  Hypocalcemia
  Knee osteoarthritis
  Male infertility
  Metabolic disorder
  Non-alcoholic fatty liver disease
  Obstructive sleep apnea
  Osteoarthritis
  Polycystic kidney disease
  Polycystic ovarian syndrome
  Prediabetes syndrome
  Prostate carcinoma
  Prostate neoplasm
  Rheumatoid arthritis
  Rickets
  Vascular disease
  Vitamin D deficiency
  X-linked dominant hypophosphatemic rickets
  Calcinosis
  Familial tumoral calcinosis
  Heart valve disorder
  Bone osteosarcoma
  Osteosarcoma
  Advanced cancer
  Chronic kidney disease
  Coronary atherosclerosis
  Prostate cancer
• UniProt ID: OSTCN_HUMAN
• Sequence:
  MRALTLLALLALAALCIAGQAGAKPSGAESSKGAAFVSKQEGSEVVKRPRRYLYQWLGAP
  VPYPDPLEPRREVCELNPDCDELADHIGFQEAYRRFYGPV
• Function: Bone protein that constitutes 1-2% of the total bone protein, and which acts as a negative regulator of bone formation. Functions to limit bone formation without impairing bone resorption or mineralization. It binds strongly to apatite and calcium ; The uncarboxylated form acts as a hormone secreted by osteoblasts, which regulates different cellular processes, such as energy metabolism, male fertility and brain development. Regulates of energy metabolism by acting as a hormone favoring pancreatic beta-cell proliferation, insulin secretion and sensitivity and energy expenditure. Uncarboxylated osteocalcin hormone also promotes testosterone production in the testes: acts as a ligand for G protein-coupled receptor GPRC6A at the surface of Leydig cells, initiating a signaling response that promotes the expression of enzymes required for testosterone synthesis in a CREB-dependent manner. Also acts as a regulator of brain development: osteocalcin hormone crosses the blood-brain barrier and acts as a ligand for GPR158 on neurons, initiating a signaling response that prevents neuronal apoptosis in the hippocampus, favors the synthesis of all monoamine neurotransmitters and inhibits that of gamma-aminobutyric acid (GABA). Osteocalcin also crosses the placenta during pregnancy and maternal osteocalcin is required for fetal brain development.
• KEGG Pathway: Parathyroid hormone synthesis, secretion and action (hsa04928)
• Reactome Pathway:
  Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus (R-HSA-159763)
  Removal of aminoterminal propeptides from gamma-carboxylated proteins (R-HSA-159782)
  RUNX2 regulates osteoblast differentiation (R-HSA-8940973)
  Gamma-carboxylation of protein precursors (R-HSA-159740)

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Osteogenesis imperfecta	DIS7XQSD	Definitive	Genetic Variation	[1]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[2]
Asthma	DISW9QNS	Strong	Biomarker	[3]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[2]
Bone disease	DISE1F82	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[5]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[5]
Chronic renal failure	DISGG7K6	Strong	Altered Expression	[6]
Congenital hypothyroidism	DISL5XVU	Strong	Biomarker	[7]
Congestive heart failure	DIS32MEA	Strong	Altered Expression	[8]
Coronary heart disease	DIS5OIP1	Strong	Biomarker	[2]
Crohn disease	DIS2C5Q8	Strong	Biomarker	[9]
Cushing disease	DISOG6P2	Strong	Altered Expression	[10]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Biomarker	[11]
End-stage renal disease	DISXA7GG	Strong	Altered Expression	[6]
High blood pressure	DISY2OHH	Strong	Genetic Variation	[12]
Hypercalcaemia	DISKQ2K7	Strong	Biomarker	[13]
Hyperglycemia	DIS0BZB5	Strong	Altered Expression	[14]
Hyperinsulinemia	DISIDWT6	Strong	Biomarker	[15]
Hyperthyroidism	DISX87ZH	Strong	Altered Expression	[16]
Hypocalcemia	DISTCK2W	Strong	Biomarker	[17]
Knee osteoarthritis	DISLSNBJ	Strong	Biomarker	[18]
Male infertility	DISY3YZZ	Strong	Biomarker	[19]
Metabolic disorder	DIS71G5H	Strong	Biomarker	[20]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Altered Expression	[21]
Obstructive sleep apnea	DIS0SVD1	Strong	Altered Expression	[22]
Osteoarthritis	DIS05URM	Strong	Altered Expression	[23]
Polycystic kidney disease	DISWS3UY	Strong	Biomarker	[24]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Altered Expression	[25]
Prediabetes syndrome	DISH2I53	Strong	Biomarker	[26]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[27]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[28]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[29]
Rickets	DISH89YF	Strong	Altered Expression	[30]
Vascular disease	DISVS67S	Strong	Biomarker	[31]
Vitamin D deficiency	DISAWKYI	Strong	Altered Expression	[30]
X-linked dominant hypophosphatemic rickets	DISU3OP6	Strong	Genetic Variation	[32]
Calcinosis	DISQP4OR	moderate	Biomarker	[33]
Familial tumoral calcinosis	DISYJZKG	moderate	Biomarker	[33]
Heart valve disorder	DIS84O7T	moderate	Biomarker	[33]
Bone osteosarcoma	DIST1004	Disputed	Altered Expression	[34]
Osteosarcoma	DISLQ7E2	Disputed	Altered Expression	[34]
Advanced cancer	DISAT1Z9	Limited	Genetic Variation	[35]
Chronic kidney disease	DISW82R7	Limited	Biomarker	[36]
Coronary atherosclerosis	DISKNDYU	Limited	Biomarker	[2]
Prostate cancer	DISF190Y	Limited	Biomarker	[27]

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Osteocalcin (BGLAP) increases the Bone density decreased ADR of Ciclosporin.	[77]
Doxorubicin	DMVP5YE	Approved	Osteocalcin (BGLAP) increases the Electrolyte imbalance ADR of Doxorubicin.	[77]
Cisplatin	DMRHGI9	Approved	Osteocalcin (BGLAP) increases the Electrolyte imbalance ADR of Cisplatin.	[77]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Osteocalcin (BGLAP).	[37]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Osteocalcin (BGLAP).	[38]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Osteocalcin (BGLAP).	[39]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Osteocalcin (BGLAP).	[40]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Osteocalcin (BGLAP).	[41]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Osteocalcin (BGLAP).	[42]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Osteocalcin (BGLAP).	[43]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Osteocalcin (BGLAP).	[44]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Osteocalcin (BGLAP).	[45]
Menadione	DMSJDTY	Approved	Menadione decreases the expression of Osteocalcin (BGLAP).	[46]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Osteocalcin (BGLAP).	[47]
Nicotine	DMWX5CO	Approved	Nicotine decreases the expression of Osteocalcin (BGLAP).	[48]
Simvastatin	DM30SGU	Approved	Simvastatin increases the expression of Osteocalcin (BGLAP).	[49]
Ifosfamide	DMCT3I8	Approved	Ifosfamide decreases the expression of Osteocalcin (BGLAP).	[50]
Alitretinoin	DMME8LH	Approved	Alitretinoin decreases the expression of Osteocalcin (BGLAP).	[51]
Cholecalciferol	DMGU74E	Approved	Cholecalciferol increases the expression of Osteocalcin (BGLAP).	[52]
Melatonin	DMKWFBT	Approved	Melatonin increases the expression of Osteocalcin (BGLAP).	[53]
Glucosamine	DM4ZLFD	Approved	Glucosamine increases the expression of Osteocalcin (BGLAP).	[54]
Budesonide	DMJIBAW	Approved	Budesonide decreases the expression of Osteocalcin (BGLAP).	[55]
Pamidronate	DMB4AVP	Approved	Pamidronate increases the expression of Osteocalcin (BGLAP).	[56]
Fluticasone propionate	DMRWLB2	Approved	Fluticasone propionate increases the expression of Osteocalcin (BGLAP).	[57]
Magnesium	DMU4ORS	Approved	Magnesium increases the expression of Osteocalcin (BGLAP).	[58]
Alendronate	DMY2KX9	Approved	Alendronate decreases the expression of Osteocalcin (BGLAP).	[60]
Falecalcitrol	DMBI9ZJ	Approved	Falecalcitrol increases the expression of Osteocalcin (BGLAP).	[61]
Berberine	DMC5Q8X	Phase 4	Berberine increases the expression of Osteocalcin (BGLAP).	[62]
Beclomethasone dipropionate	DM5NW1E	Phase 4	Beclomethasone dipropionate decreases the expression of Osteocalcin (BGLAP).	[63]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Osteocalcin (BGLAP).	[64]
Atorvastatin	DMF28YC	Phase 3 Trial	Atorvastatin increases the expression of Osteocalcin (BGLAP).	[65]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Osteocalcin (BGLAP).	[66]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Osteocalcin (BGLAP).	[68]
Lexacalcitol	DMJ3ZT8	Discontinued in Phase 2	Lexacalcitol increases the expression of Osteocalcin (BGLAP).	[51]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Osteocalcin (BGLAP).	[69]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride affects the expression of Osteocalcin (BGLAP).	[70]
U0126	DM31OGF	Investigative	U0126 decreases the expression of Osteocalcin (BGLAP).	[71]
	DM9CEI5		increases the expression of Osteocalcin (BGLAP).	[52]
PD98059	DMZC90M	Investigative	PD98059 decreases the expression of Osteocalcin (BGLAP).	[40]
Naringin	DM4DG1Y	Investigative	Naringin increases the expression of Osteocalcin (BGLAP).	[72]
3-aminobenzamide	DM7P3IZ	Investigative	3-aminobenzamide increases the expression of Osteocalcin (BGLAP).	[73]
Alpha-ketoglutaric acid	DM5LFYN	Investigative	Alpha-ketoglutaric acid increases the expression of Osteocalcin (BGLAP).	[74]
ODQ	DMSAJO8	Investigative	ODQ decreases the expression of Osteocalcin (BGLAP).	[75]
phenamil	DMJLUFM	Investigative	phenamil increases the expression of Osteocalcin (BGLAP).	[76]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Norethindrone	DMTY169	Approved	Norethindrone increases the secretion of Osteocalcin (BGLAP).	[59]

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 decreases the methylation of Osteocalcin (BGLAP).	[67]

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