Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTY7G382)

• DOT Name: Collagen alpha-2(I) chain (COL1A2)
• Synonyms: Alpha-2 type I collagen
• Gene Name: COL1A2
• Related Disease:
  Ehlers-Danlos syndrome, arthrochalasia type
  Ehlers-danlos syndrome, arthrochalasia type, 2
  Ehlers-Danlos syndrome, cardiac valvular type
  Osteogenesis imperfecta type 1
  Osteogenesis imperfecta type 2
  Osteogenesis imperfecta type 3
  Osteogenesis imperfecta type 4
  Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2
  Ehlers-Danlos/osteogenesis imperfecta syndrome
  High bone mass osteogenesis imperfecta
• UniProt ID: CO1A2_HUMAN
• PDB ID: 5CTD; 5CTI; 5CVA; 6JEC
• Pfam ID: PF01410 ; PF01391
• Sequence:
  MLSFVDTRTLLLLAVTLCLATCQSLQEETVRKGPAGDRGPRGERGPPGPPGRDGEDGPTG
  PPGPPGPPGPPGLGGNFAAQYDGKGVGLGPGPMGLMGPRGPPGAAGAPGPQGFQGPAGEP
  GEPGQTGPAGARGPAGPPGKAGEDGHPGKPGRPGERGVVGPQGARGFPGTPGLPGFKGIR
  GHNGLDGLKGQPGAPGVKGEPGAPGENGTPGQTGARGLPGERGRVGAPGPAGARGSDGSV
  GPVGPAGPIGSAGPPGFPGAPGPKGEIGAVGNAGPAGPAGPRGEVGLPGLSGPVGPPGNP
  GANGLTGAKGAAGLPGVAGAPGLPGPRGIPGPVGAAGATGARGLVGEPGPAGSKGESGNK
  GEPGSAGPQGPPGPSGEEGKRGPNGEAGSAGPPGPPGLRGSPGSRGLPGADGRAGVMGPP
  GSRGASGPAGVRGPNGDAGRPGEPGLMGPRGLPGSPGNIGPAGKEGPVGLPGIDGRPGPI
  GPAGARGEPGNIGFPGPKGPTGDPGKNGDKGHAGLAGARGAPGPDGNNGAQGPPGPQGVQ
  GGKGEQGPPGPPGFQGLPGPSGPAGEVGKPGERGLHGEFGLPGPAGPRGERGPPGESGAA
  GPTGPIGSRGPSGPPGPDGNKGEPGVVGAVGTAGPSGPSGLPGERGAAGIPGGKGEKGEP
  GLRGEIGNPGRDGARGAPGAVGAPGPAGATGDRGEAGAAGPAGPAGPRGSPGERGEVGPA
  GPNGFAGPAGAAGQPGAKGERGAKGPKGENGVVGPTGPVGAAGPAGPNGPPGPAGSRGDG
  GPPGMTGFPGAAGRTGPPGPSGISGPPGPPGPAGKEGLRGPRGDQGPVGRTGEVGAVGPP
  GFAGEKGPSGEAGTAGPPGTPGPQGLLGAPGILGLPGSRGERGLPGVAGAVGEPGPLGIA
  GPPGARGPPGAVGSPGVNGAPGEAGRDGNPGNDGPPGRDGQPGHKGERGYPGNIGPVGAA
  GAPGPHGPVGPAGKHGNRGETGPSGPVGPAGAVGPRGPSGPQGIRGDKGEPGEKGPRGLP
  GLKGHNGLQGLPGIAGHHGDQGAPGSVGPAGPRGPAGPSGPAGKDGRTGHPGTVGPAGIR
  GPQGHQGPAGPPGPPGPPGPPGVSGGGYDFGYDGDFYRADQPRSAPSLRPKDYEVDATLK
  SLNNQIETLLTPEGSRKNPARTCRDLRLSHPEWSSGYYWIDPNQGCTMDAIKVYCDFSTG
  ETCIRAQPENIPAKNWYRSSKDKKHVWLGETINAGSQFEYNVEGVTSKEMATQLAFMRLL
  ANYASQNITYHCKNSIAYMDEETGNLKKAVILQGSNDVELVAEGNSRFTYTVLVDGCSKK
  TNEWGKTIIEYKTNKPSRLPFLDIAPLDIGGADQEFFVDIGPVCFK
• Function: Type I collagen is a member of group I collagen (fibrillar forming collagen).
• Tissue Specificity: Forms the fibrils of tendon, ligaments and bones. In bones the fibrils are mineralized with calcium hydroxyapatite.
• KEGG Pathway:
  PI3K-Akt sig.ling pathway (hsa04151)
  Focal adhesion (hsa04510)
  ECM-receptor interaction (hsa04512)
  Platelet activation (hsa04611)
  Cytoskeleton in muscle cells (hsa04820)
  Relaxin sig.ling pathway (hsa04926)
  AGE-RAGE sig.ling pathway in diabetic complications (hsa04933)
  Protein digestion and absorption (hsa04974)
  Amoebiasis (hsa05146)
  Human papillomavirus infection (hsa05165)
  Proteoglycans in cancer (hsa05205)
  Diabetic cardiomyopathy (hsa05415)
• Reactome Pathway:
  Collagen degradation (R-HSA-1442490)
  Extracellular matrix organization (R-HSA-1474244)
  Collagen biosynthesis and modifying enzymes (R-HSA-1650814)
  Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933)
  Assembly of collagen fibrils and other multimeric structures (R-HSA-2022090)
  Cell surface interactions at the vascular wall (R-HSA-202733)
  Integrin cell surface interactions (R-HSA-216083)
  SMAD2/SMAD3 (R-HSA-2173796)
  Anchoring fibril formation (R-HSA-2214320)
  Crosslinking of collagen fibrils (R-HSA-2243919)
  Syndecan interactions (R-HSA-3000170)
  Non-integrin membrane-ECM interactions (R-HSA-3000171)
  ECM proteoglycans (R-HSA-3000178)
  Scavenging by Class A Receptors (R-HSA-3000480)
  GP1b-IX-V activation signalling (R-HSA-430116)
  Interleukin-4 and Interleukin-13 signaling (R-HSA-6785807)
  Platelet Adhesion to exposed collagen (R-HSA-75892)
  Platelet Aggregation (Plug Formation) (R-HSA-76009)
  MET activates PTK2 signaling (R-HSA-8874081)
  Collagen chain trimerization (R-HSA-8948216)
  GPVI-mediated activation cascade (R-HSA-114604)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Ehlers-Danlos syndrome, arthrochalasia type	DISSQ1CQ	Definitive	Autosomal dominant	[1]
Ehlers-danlos syndrome, arthrochalasia type, 2	DIS6WZCC	Definitive	Autosomal dominant	[2]
Ehlers-Danlos syndrome, cardiac valvular type	DISTP32F	Definitive	Autosomal recessive	[1]
Osteogenesis imperfecta type 1	DISPEDS3	Definitive	Autosomal dominant	[1]
Osteogenesis imperfecta type 2	DISMGSS3	Definitive	Autosomal dominant	[1]
Osteogenesis imperfecta type 3	DISFJVSJ	Definitive	Autosomal dominant	[1]
Osteogenesis imperfecta type 4	DIS8S46L	Definitive	Autosomal dominant	[1]
Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2	DISMVYJG	Moderate	Autosomal dominant	[1]
Ehlers-Danlos/osteogenesis imperfecta syndrome	DISK4W8M	Supportive	Autosomal dominant	[3]
High bone mass osteogenesis imperfecta	DIS9U2CU	Supportive	Autosomal dominant	[4]

This DOT Affected the Drug Response of 5 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Collagen alpha-2(I) chain (COL1A2) increases the response to substance of Doxorubicin.	[37]
Cisplatin	DMRHGI9	Approved	Collagen alpha-2(I) chain (COL1A2) increases the response to substance of Cisplatin.	[37]
Methotrexate	DM2TEOL	Approved	Collagen alpha-2(I) chain (COL1A2) increases the response to substance of Methotrexate.	[37]
Paclitaxel	DMLB81S	Approved	Collagen alpha-2(I) chain (COL1A2) increases the response to substance of Paclitaxel.	[37]
Topotecan	DMP6G8T	Approved	Collagen alpha-2(I) chain (COL1A2) increases the response to substance of Topotecan.	[37]

40 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 Collagen alpha-2(I) chain (COL1A2).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Collagen alpha-2(I) chain (COL1A2).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Collagen alpha-2(I) chain (COL1A2).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Collagen alpha-2(I) chain (COL1A2).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Collagen alpha-2(I) chain (COL1A2).	[9]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Collagen alpha-2(I) chain (COL1A2).	[10]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Collagen alpha-2(I) chain (COL1A2).	[11]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Collagen alpha-2(I) chain (COL1A2).	[12]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Collagen alpha-2(I) chain (COL1A2).	[6]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Collagen alpha-2(I) chain (COL1A2).	[13]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Collagen alpha-2(I) chain (COL1A2).	[14]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Collagen alpha-2(I) chain (COL1A2).	[12]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Collagen alpha-2(I) chain (COL1A2).	[15]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Collagen alpha-2(I) chain (COL1A2).	[16]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Collagen alpha-2(I) chain (COL1A2).	[17]
Malathion	DMXZ84M	Approved	Malathion increases the expression of Collagen alpha-2(I) chain (COL1A2).	[18]
Phenytoin	DMNOKBV	Approved	Phenytoin increases the expression of Collagen alpha-2(I) chain (COL1A2).	[19]
Aldosterone	DM9S2JW	Approved	Aldosterone increases the expression of Collagen alpha-2(I) chain (COL1A2).	[20]
Magnesium	DMU4ORS	Approved	Magnesium increases the expression of Collagen alpha-2(I) chain (COL1A2).	[21]
Ademetionine	DMYQDBO	Approved	Ademetionine decreases the expression of Collagen alpha-2(I) chain (COL1A2).	[22]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Collagen alpha-2(I) chain (COL1A2).	[12]
Coprexa	DMA0WEK	Phase 3	Coprexa increases the expression of Collagen alpha-2(I) chain (COL1A2).	[24]
HMPL-004	DM29XGY	Phase 3	HMPL-004 decreases the expression of Collagen alpha-2(I) chain (COL1A2).	[25]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Collagen alpha-2(I) chain (COL1A2).	[12]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Collagen alpha-2(I) chain (COL1A2).	[26]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Collagen alpha-2(I) chain (COL1A2).	[27]
Piperazinyl methyl quinazolinone derivative 2	DM913KS	Patented	Piperazinyl methyl quinazolinone derivative 2 increases the expression of Collagen alpha-2(I) chain (COL1A2).	[28]
Methylthioadenosine	DMC8J6F	Terminated	Methylthioadenosine decreases the expression of Collagen alpha-2(I) chain (COL1A2).	[22]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Collagen alpha-2(I) chain (COL1A2).	[29]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Collagen alpha-2(I) chain (COL1A2).	[30]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Collagen alpha-2(I) chain (COL1A2).	[31]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Collagen alpha-2(I) chain (COL1A2).	[32]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Collagen alpha-2(I) chain (COL1A2).	[33]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Collagen alpha-2(I) chain (COL1A2).	[6]
D-glucose	DMMG2TO	Investigative	D-glucose increases the expression of Collagen alpha-2(I) chain (COL1A2).	[34]
NAPQI	DM8F5LR	Investigative	NAPQI increases the expression of Collagen alpha-2(I) chain (COL1A2).	[35]
I-BET151	DMYRUH2	Investigative	I-BET151 decreases the expression of Collagen alpha-2(I) chain (COL1A2).	[26]
PFI-1	DMVFK3J	Investigative	PFI-1 decreases the expression of Collagen alpha-2(I) chain (COL1A2).	[26]
(L-)-S-adenosyl-L-homocysteine	DMDUN83	Investigative	(L-)-S-adenosyl-L-homocysteine decreases the expression of Collagen alpha-2(I) chain (COL1A2).	[22]
ODQ	DMSAJO8	Investigative	ODQ decreases the expression of Collagen alpha-2(I) chain (COL1A2).	[36]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Resveratrol	DM3RWXL	Phase 3	Resveratrol affects the secretion of Collagen alpha-2(I) chain (COL1A2).	[23]

References

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