Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNMMA2P)

• DOT Name: von Willebrand factor
• Synonyms: vWF
• Gene Name: VWF
• Related Disease:
  Hereditary von Willebrand disease
  Von Willebrand disease 2
  Von Willebrand disease type 2B
  Von Willebrand disease 1
  Von Willebrand disease 3
  Von Willebrand disease type 2A
  Von Willebrand disease type 2M
  Von Willebrand disease type 2N
• UniProt ID: VWF_HUMAN
• PDB ID: 1AO3 ; 1ATZ ; 1AUQ ; 1FE8 ; 1FNS ; 1IJB ; 1IJK ; 1M10 ; 1OAK ; 1SQ0 ; 1U0N ; 1UEX ; 2ADF ; 2MHP ; 2MHQ ; 3GXB ; 3HXO ; 3HXQ ; 3PPV ; 3PPW ; 3PPX ; 3PPY ; 3ZQK ; 4C29 ; 4C2A ; 4C2B ; 4DMU ; 4NT5 ; 5BV8 ; 6FWN ; 6N29 ; 7EOW ; 7F49 ; 7KWO ; 7P4N ; 7PMV ; 7PNF ; 7ZWH ; 8D3C ; 8D3D
• Pfam ID: PF08742 ; PF01826 ; PF00092 ; PF16164 ; PF00093 ; PF00094
• Sequence:
  MIPARFAGVLLALALILPGTLCAEGTRGRSSTARCSLFGSDFVNTFDGSMYSFAGYCSYL
  LAGGCQKRSFSIIGDFQNGKRVSLSVYLGEFFDIHLFVNGTVTQGDQRVSMPYASKGLYL
  ETEAGYYKLSGEAYGFVARIDGSGNFQVLLSDRYFNKTCGLCGNFNIFAEDDFMTQEGTL
  TSDPYDFANSWALSSGEQWCERASPPSSSCNISSGEMQKGLWEQCQLLKSTSVFARCHPL
  VDPEPFVALCEKTLCECAGGLECACPALLEYARTCAQEGMVLYGWTDHSACSPVCPAGME
  YRQCVSPCARTCQSLHINEMCQERCVDGCSCPEGQLLDEGLCVESTECPCVHSGKRYPPG
  TSLSRDCNTCICRNSQWICSNEECPGECLVTGQSHFKSFDNRYFTFSGICQYLLARDCQD
  HSFSIVIETVQCADDRDAVCTRSVTVRLPGLHNSLVKLKHGAGVAMDGQDVQLPLLKGDL
  RIQHTVTASVRLSYGEDLQMDWDGRGRLLVKLSPVYAGKTCGLCGNYNGNQGDDFLTPSG
  LAEPRVEDFGNAWKLHGDCQDLQKQHSDPCALNPRMTRFSEEACAVLTSPTFEACHRAVS
  PLPYLRNCRYDVCSCSDGRECLCGALASYAAACAGRGVRVAWREPGRCELNCPKGQVYLQ
  CGTPCNLTCRSLSYPDEECNEACLEGCFCPPGLYMDERGDCVPKAQCPCYYDGEIFQPED
  IFSDHHTMCYCEDGFMHCTMSGVPGSLLPDAVLSSPLSHRSKRSLSCRPPMVKLVCPADN
  LRAEGLECTKTCQNYDLECMSMGCVSGCLCPPGMVRHENRCVALERCPCFHQGKEYAPGE
  TVKIGCNTCVCQDRKWNCTDHVCDATCSTIGMAHYLTFDGLKYLFPGECQYVLVQDYCGS
  NPGTFRILVGNKGCSHPSVKCKKRVTILVEGGEIELFDGEVNVKRPMKDETHFEVVESGR
  YIILLLGKALSVVWDRHLSISVVLKQTYQEKVCGLCGNFDGIQNNDLTSSNLQVEEDPVD
  FGNSWKVSSQCADTRKVPLDSSPATCHNNIMKQTMVDSSCRILTSDVFQDCNKLVDPEPY
  LDVCIYDTCSCESIGDCACFCDTIAAYAHVCAQHGKVVTWRTATLCPQSCEERNLRENGY
  ECEWRYNSCAPACQVTCQHPEPLACPVQCVEGCHAHCPPGKILDELLQTCVDPEDCPVCE
  VAGRRFASGKKVTLNPSDPEHCQICHCDVVNLTCEACQEPGGLVVPPTDAPVSPTTLYVE
  DISEPPLHDFYCSRLLDLVFLLDGSSRLSEAEFEVLKAFVVDMMERLRISQKWVRVAVVE
  YHDGSHAYIGLKDRKRPSELRRIASQVKYAGSQVASTSEVLKYTLFQIFSKIDRPEASRI
  TLLLMASQEPQRMSRNFVRYVQGLKKKKVIVIPVGIGPHANLKQIRLIEKQAPENKAFVL
  SSVDELEQQRDEIVSYLCDLAPEAPPPTLPPDMAQVTVGPGLLGVSTLGPKRNSMVLDVA
  FVLEGSDKIGEADFNRSKEFMEEVIQRMDVGQDSIHVTVLQYSYMVTVEYPFSEAQSKGD
  ILQRVREIRYQGGNRTNTGLALRYLSDHSFLVSQGDREQAPNLVYMVTGNPASDEIKRLP
  GDIQVVPIGVGPNANVQELERIGWPNAPILIQDFETLPREAPDLVLQRCCSGEGLQIPTL
  SPAPDCSQPLDVILLLDGSSSFPASYFDEMKSFAKAFISKANIGPRLTQVSVLQYGSITT
  IDVPWNVVPEKAHLLSLVDVMQREGGPSQIGDALGFAVRYLTSEMHGARPGASKAVVILV
  TDVSVDSVDAAADAARSNRVTVFPIGIGDRYDAAQLRILAGPAGDSNVVKLQRIEDLPTM
  VTLGNSFLHKLCSGFVRICMDEDGNEKRPGDVWTLPDQCHTVTCQPDGQTLLKSHRVNCD
  RGLRPSCPNSQSPVKVEETCGCRWTCPCVCTGSSTRHIVTFDGQNFKLTGSCSYVLFQNK
  EQDLEVILHNGACSPGARQGCMKSIEVKHSALSVELHSDMEVTVNGRLVSVPYVGGNMEV
  NVYGAIMHEVRFNHLGHIFTFTPQNNEFQLQLSPKTFASKTYGLCGICDENGANDFMLRD
  GTVTTDWKTLVQEWTVQRPGQTCQPILEEQCLVPDSSHCQVLLLPLFAECHKVLAPATFY
  AICQQDSCHQEQVCEVIASYAHLCRTNGVCVDWRTPDFCAMSCPPSLVYNHCEHGCPRHC
  DGNVSSCGDHPSEGCFCPPDKVMLEGSCVPEEACTQCIGEDGVQHQFLEAWVPDHQPCQI
  CTCLSGRKVNCTTQPCPTAKAPTCGLCEVARLRQNADQCCPEYECVCDPVSCDLPPVPHC
  ERGLQPTLTNPGECRPNFTCACRKEECKRVSPPSCPPHRLPTLRKTQCCDEYECACNCVN
  STVSCPLGYLASTATNDCGCTTTTCLPDKVCVHRSTIYPVGQFWEEGCDVCTCTDMEDAV
  MGLRVAQCSQKPCEDSCRSGFTYVLHEGECCGRCLPSACEVVTGSPRGDSQSSWKSVGSQ
  WASPENPCLINECVRVKEEVFIQQRNVSCPQLEVPVCPSGFQLSCKTSACCPSCRCERME
  ACMLNGTVIGPGKTVMIDVCTTCRCMVQVGVISGFKLECRKTTCNPCPLGYKEENNTGEC
  CGRCLPTACTIQLRGGQIMTLKRDETLQDGCDTHFCKVNERGEYFWEKRVTGCPPFDEHK
  CLAEGGKIMKIPGTCCDTCEEPECNDITARLQYVKVGSCKSEVEVDIHYCQGKCASKAMY
  SIDINDVQDQCSCCSPTRTEPMQVALHCTNGSVVYHEVLNAMECKCSPRKCSK
• Function: Important in the maintenance of hemostasis, it promotes adhesion of platelets to the sites of vascular injury by forming a molecular bridge between sub-endothelial collagen matrix and platelet-surface receptor complex GPIb-IX-V. Also acts as a chaperone for coagulation factor VIII, delivering it to the site of injury, stabilizing its heterodimeric structure and protecting it from premature clearance from plasma.
• Tissue Specificity: Plasma.
• KEGG Pathway:
  PI3K-Akt sig.ling pathway (hsa04151)
  Focal adhesion (hsa04510)
  ECM-receptor interaction (hsa04512)
  Complement and coagulation cascades (hsa04610)
  Platelet activation (hsa04611)
  Neutrophil extracellular trap formation (hsa04613)
  Human papillomavirus infection (hsa05165)
  Coro.virus disease - COVID-19 (hsa05171)
• Reactome Pathway:
  Intrinsic Pathway of Fibrin Clot Formation (R-HSA-140837)
  Integrin cell surface interactions (R-HSA-216083)
  Integrin signaling (R-HSA-354192)
  GRB2 (R-HSA-354194)
  p130Cas linkage to MAPK signaling for integrins (R-HSA-372708)
  GP1b-IX-V activation signalling (R-HSA-430116)
  MAP2K and MAPK activation (R-HSA-5674135)
  Signaling by moderate kinase activity BRAF mutants (R-HSA-6802946)
  Signaling by high-kinase activity BRAF mutants (R-HSA-6802948)
  Signaling by BRAF and RAF1 fusions (R-HSA-6802952)
  Paradoxical activation of RAF signaling by kinase inactive BRAF (R-HSA-6802955)
  Platelet Adhesion to exposed collagen (R-HSA-75892)
  Platelet Aggregation (Plug Formation) (R-HSA-76009)
  Signaling downstream of RAS mutants (R-HSA-9649948)
  Signaling by RAF1 mutants (R-HSA-9656223)
  Defective F8 cleavage by thrombin (R-HSA-9672391)
  Defective F8 binding to von Willebrand factor (R-HSA-9672393)
  Platelet degranulation (R-HSA-114608)
• BioCyc Pathway: MetaCyc:ENSG00000110799-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hereditary von Willebrand disease	DIS0XCII	Definitive	Autosomal dominant	[1]
Von Willebrand disease 2	DISEYUBR	Definitive	Autosomal dominant	[2]
Von Willebrand disease type 2B	DISLHZRK	Definitive	Autosomal dominant	[1]
Von Willebrand disease 1	DISUGLZA	Strong	Autosomal dominant	[3]
Von Willebrand disease 3	DISPVXSD	Supportive	Autosomal recessive	[4]
Von Willebrand disease type 2A	DISTAHJN	Supportive	Autosomal dominant	[4]
Von Willebrand disease type 2M	DISUIER4	Supportive	Autosomal dominant	[4]
Von Willebrand disease type 2N	DIS7S2QL	Supportive	Autosomal recessive	[4]

This DOT Affected the Drug Response of 4 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	von Willebrand factor increases the Haemolysis ADR of Ciclosporin.	[33]
Selenium	DM25CGV	Approved	von Willebrand factor increases the Blood and lymphatic system disorders ADR of Selenium.	[33]
Paclitaxel	DMLB81S	Approved	von Willebrand factor increases the Vascular disorders ADR of Paclitaxel.	[33]
Beta-carotene	DM0RXBT	Approved	von Willebrand factor increases the Blood and lymphatic system disorders ADR of Beta-carotene.	[33]

25 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 von Willebrand factor.	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of von Willebrand factor.	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of von Willebrand factor.	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of von Willebrand factor.	[8]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of von Willebrand factor.	[9]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of von Willebrand factor.	[11]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of von Willebrand factor.	[12]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of von Willebrand factor.	[13]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of von Willebrand factor.	[14]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of von Willebrand factor.	[15]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of von Willebrand factor.	[16]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of von Willebrand factor.	[17]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol decreases the expression of von Willebrand factor.	[18]
Cocaine	DMSOX7I	Approved	Cocaine increases the expression of von Willebrand factor.	[19]
Gemcitabine	DMSE3I7	Approved	Gemcitabine decreases the expression of von Willebrand factor.	[20]
Hydrocortisone	DMGEMB7	Approved	Hydrocortisone increases the expression of von Willebrand factor.	[21]
Methylprednisolone	DM4BDON	Approved	Methylprednisolone decreases the expression of von Willebrand factor.	[22]
Perindopril	DMOPZDT	Approved	Perindopril decreases the expression of von Willebrand factor.	[23]
Desmopressin	DMS3GVE	Approved	Desmopressin increases the activity of von Willebrand factor.	[24]
Atorvastatin	DMF28YC	Phase 3 Trial	Atorvastatin increases the expression of von Willebrand factor.	[25]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of von Willebrand factor.	[26]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of von Willebrand factor.	[28]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of von Willebrand factor.	[29]
D-glucose	DMMG2TO	Investigative	D-glucose decreases the expression of von Willebrand factor.	[30]
acrolein	DMAMCSR	Investigative	acrolein decreases the expression of von Willebrand factor.	[31]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of von Willebrand factor.	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of von Willebrand factor.	[27]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
L-methionine	DME8G1U	Investigative	L-methionine increases the degradation of von Willebrand factor.	[32]

References

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