Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPCOYL6)

• DOT Name: Filamin-B (FLNB)
• Synonyms: FLN-B; ABP-278; ABP-280 homolog; Actin-binding-like protein; Beta-filamin; Filamin homolog 1; Fh1; Filamin-3; Thyroid autoantigen; Truncated actin-binding protein; Truncated ABP
• Gene Name: FLNB
• Related Disease:
  Atelosteogenesis type I
  Atelosteogenesis type III
  Behcet disease
  Larsen syndrome
  Psoriasis
  Spondylocarpotarsal synostosis syndrome
  Analgesia
  Ankylosing spondylitis
  Autoimmune disease
  Boomerang dysplasia
  Breast carcinoma
  Carcinoma
  Carcinoma of esophagus
  Cervical cancer
  Cervical carcinoma
  Coeliac disease
  Crohn disease
  Eating disorder
  Familial hyperaldosteronism
  Graves disease
  Hashimoto thyroiditis
  Hepatitis B virus infection
  Hepatocellular carcinoma
  Human papillomavirus infection
  Hyperaldosteronism, familial, type IV
  Juvenile idiopathic arthritis
  Lung cancer
  Lung carcinoma
  Lung neoplasm
  Neoplasm
  OPTN-related open angle glaucoma
  Osteochondrodysplasia
  Renal cell carcinoma
  Rheumatoid arthritis
  Tuberculosis
  Type-1 diabetes
  Ulcerative colitis
  Metastatic malignant neoplasm
  Pulmonary tuberculosis
  Advanced cancer
  Atopic dermatitis
  Breast cancer
  Clubfoot
  Dementia
  Hepatitis C virus infection
  Herpes simplex infection
  Melanoma
• UniProt ID: FLNB_HUMAN
• PDB ID: 2DI8; 2DI9; 2DIA; 2DIB; 2DIC; 2DJ4; 2DLG; 2DMB; 2DMC; 2E9I; 2E9J; 2EE6; 2EE9; 2EEA; 2EEB; 2EEC; 2EED; 2WA5; 2WA6; 2WA7; 3FER; 4B7L; 5DCP
• Pfam ID: PF00307 ; PF00630
• Sequence:
  MPVTEKDLAEDAPWKKIQQNTFTRWCNEHLKCVNKRIGNLQTDLSDGLRLIALLEVLSQK
  RMYRKYHQRPTFRQMQLENVSVALEFLDRESIKLVSIDSKAIVDGNLKLILGLVWTLILH
  YSISMPVWEDEGDDDAKKQTPKQRLLGWIQNKIPYLPITNFNQNWQDGKALGALVDSCAP
  GLCPDWESWDPQKPVDNAREAMQQADDWLGVPQVITPEEIIHPDVDEHSVMTYLSQFPKA
  KLKPGAPLKPKLNPKKARAYGRGIEPTGNMVKQPAKFTVDTISAGQGDVMVFVEDPEGNK
  EEAQVTPDSDKNKTYSVEYLPKVTGLHKVTVLFAGQHISKSPFEVSVDKAQGDASKVTAK
  GPGLEAVGNIANKPTYFDIYTAGAGVGDIGVEVEDPQGKNTVELLVEDKGNQVYRCVYKP
  MQPGPHVVKIFFAGDTIPKSPFVVQVGEACNPNACRASGRGLQPKGVRIRETTDFKVDTK
  AAGSGELGVTMKGPKGLEELVKQKDFLDGVYAFEYYPSTPGRYSIAITWGGHHIPKSPFE
  VQVGPEAGMQKVRAWGPGLHGGIVGRSADFVVESIGSEVGSLGFAIEGPSQAKIEYNDQN
  DGSCDVKYWPKEPGEYAVHIMCDDEDIKDSPYMAFIHPATGGYNPDLVRAYGPGLEKSGC
  IVNNLAEFTVDPKDAGKAPLKIFAQDGEGQRIDIQMKNRMDGTYACSYTPVKAIKHTIAV
  VWGGVNIPHSPYRVNIGQGSHPQKVKVFGPGVERSGLKANEPTHFTVDCTEAGEGDVSVG
  IKCDARVLSEDEEDVDFDIIHNANDTFTVKYVPPAAGRYTIKVLFASQEIPASPFRVKVD
  PSHDASKVKAEGPGLSKAGVENGKPTHFTVYTKGAGKAPLNVQFNSPLPGDAVKDLDIID
  NYDYSHTVKYTPTQQGNMQVLVTYGGDPIPKSPFTVGVAAPLDLSKIKLNGLENRVEVGK
  DQEFTVDTRGAGGQGKLDVTILSPSRKVVPCLVTPVTGRENSTAKFIPREEGLYAVDVTY
  DGHPVPGSPYTVEASLPPDPSKVKAHGPGLEGGLVGKPAEFTIDTKGAGTGGLGLTVEGP
  CEAKIECSDNGDGTCSVSYLPTKPGEYFVNILFEEVHIPGSPFKADIEMPFDPSKVVASG
  PGLEHGKVGEAGLLSVDCSEAGPGALGLEAVSDSGTKAEVSIQNNKDGTYAVTYVPLTAG
  MYTLTMKYGGELVPHFPARVKVEPAVDTSRIKVFGPGIEGKDVFREATTDFTVDSRPLTQ
  VGGDHIKAHIANPSGASTECFVTDNADGTYQVEYTPFEKGLHVVEVTYDDVPIPNSPFKV
  AVTEGCQPSRVQAQGPGLKEAFTNKPNVFTVVTRGAGIGGLGITVEGPSESKINCRDNKD
  GSCSAEYIPFAPGDYDVNITYGGAHIPGSPFRVPVKDVVDPSKVKIAGPGLGSGVRARVL
  QSFTVDSSKAGLAPLEVRVLGPRGLVEPVNVVDNGDGTHTVTYTPSQEGPYMVSVKYADE
  EIPRSPFKVKVLPTYDASKVTASGPGLSSYGVPASLPVDFAIDARDAGEGLLAVQITDQE
  GKPKRAIVHDNKDGTYAVTYIPDKTGRYMIGVTYGGDDIPLSPYRIRATQTGDASKCLAT
  GPGIASTVKTGEEVGFVVDAKTAGKGKVTCTVLTPDGTEAEADVIENEDGTYDIFYTAAK
  PGTYVIYVRFGGVDIPNSPFTVMATDGEVTAVEEAPVNACPPGFRPWVTEEAYVPVSDMN
  GLGFKPFDLVIPFAVRKGEITGEVHMPSGKTATPEIVDNKDGTVTVRYAPTEVGLHEMHI
  KYMGSHIPESPLQFYVNYPNSGSVSAYGPGLVYGVANKTATFTIVTEDAGEGGLDLAIEG
  PSKAEISCIDNKDGTCTVTYLPTLPGDYSILVKYNDKHIPGSPFTAKITDDSRRCSQVKL
  GSAADFLLDISETDLSSLTASIKAPSGRDEPCLLKRLPNNHIGISFIPREVGEHLVSIKK
  NGNHVANSPVSIMVVQSEIGDARRAKVYGRGLSEGRTFEMSDFIVDTRDAGYGGISLAVE
  GPSKVDIQTEDLEDGTCKVSYFPTVPGVYIVSTKFADEHVPGSPFTVKISGEGRVKESIT
  RTSRAPSVATVGSICDLNLKIPEINSSDMSAHVTSPSGRVTEAEIVPMGKNSHCVRFVPQ
  EMGVHTVSVKYRGQHVTGSPFQFTVGPLGEGGAHKVRAGGPGLERGEAGVPAEFSIWTRE
  AGAGGLSIAVEGPSKAEITFDDHKNGSCGVSYIAQEPGNYEVSIKFNDEHIPESPYLVPV
  IAPSDDARRLTVMSLQESGLKVNQPASFAIRLNGAKGKIDAKVHSPSGAVEECHVSELEP
  DKYAVRFIPHENGVHTIDVKFNGSHVVGSPFKVRVGEPGQAGNPALVSAYGTGLEGGTTG
  IQSEFFINTTRAGPGTLSVTIEGPSKVKMDCQETPEGYKVMYTPMAPGNYLISVKYGGPN
  HIVGSPFKAKVTGQRLVSPGSANETSSILVESVTRSSTETCYSAIPKASSDASKVTSKGA
  GLSKAFVGQKSSFLVDCSKAGSNMLLIGVHGPTTPCEEVSMKHVGNQQYNVTYVVKERGD
  YVLAVKWGEEHIPGSPFHVTVP
• Function: Connects cell membrane constituents to the actin cytoskeleton. May promote orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins. Anchors various transmembrane proteins to the actin cytoskeleton. Interaction with FLNA may allow neuroblast migration from the ventricular zone into the cortical plate. Various interactions and localizations of isoforms affect myotube morphology and myogenesis. Isoform 6 accelerates muscle differentiation in vitro.
• Tissue Specificity: Ubiquitous. Isoform 1 and isoform 2 are expressed in placenta, bone marrow, brain, umbilical vein endothelial cells (HUVEC), retina and skeletal muscle. Isoform 1 is predominantly expressed in prostate, uterus, liver, thyroid, stomach, lymph node, small intestine, spleen, skeletal muscle, kidney, placenta, pancreas, heart, lung, platelets, endothelial cells, megakaryocytic and erythroleukemic cell lines. Isoform 2 is predominantly expressed in spinal cord, platelet and Daudi cells. Also expressed in thyroid adenoma, neurofibrillary tangles (NFT), senile plaques in the hippocampus and cerebral cortex in Alzheimer disease (AD). Isoform 3 and isoform 6 are expressed predominantly in lung, heart, skeletal muscle, testis, spleen, thymus and leukocytes. Isoform 4 and isoform 5 are expressed in heart.
• KEGG Pathway: Focal adhesion (hsa04510)
• Reactome Pathway: ISG15 antiviral mechanism (R-HSA-1169408)

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Atelosteogenesis type I	DISZKSYK	Definitive	Autosomal dominant	[1]
Atelosteogenesis type III	DISG0S0K	Definitive	Autosomal dominant	[1]
Behcet disease	DISSYMBS	Definitive	Biomarker	[2]
Larsen syndrome	DISDRPMA	Definitive	Mitochondrial	[3]
Psoriasis	DIS59VMN	Definitive	Genetic Variation	[4]
Spondylocarpotarsal synostosis syndrome	DISF9VP3	Definitive	Autosomal recessive	[5]
Analgesia	DISK3TVI	Strong	Biomarker	[6]
Ankylosing spondylitis	DISRC6IR	Strong	Genetic Variation	[7]
Autoimmune disease	DISORMTM	Strong	Biomarker	[8]
Boomerang dysplasia	DISXZCLW	Strong	Autosomal dominant	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[9]
Carcinoma	DISH9F1N	Strong	Altered Expression	[10]
Carcinoma of esophagus	DISS6G4D	Strong	Biomarker	[11]
Cervical cancer	DISFSHPF	Strong	Genetic Variation	[12]
Cervical carcinoma	DIST4S00	Strong	Genetic Variation	[12]
Coeliac disease	DISIY60C	Strong	Genetic Variation	[13]
Crohn disease	DIS2C5Q8	Strong	Genetic Variation	[14]
Eating disorder	DISVGXN0	Strong	Genetic Variation	[15]
Familial hyperaldosteronism	DIS9R9LI	Strong	Genetic Variation	[16]
Graves disease	DISU4KOQ	Strong	Biomarker	[17]
Hashimoto thyroiditis	DIS77CDF	Strong	Biomarker	[18]
Hepatitis B virus infection	DISLQ2XY	Strong	Altered Expression	[19]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[20]
Human papillomavirus infection	DISX61LX	Strong	Genetic Variation	[21]
Hyperaldosteronism, familial, type IV	DIS069LK	Strong	Biomarker	[16]
Juvenile idiopathic arthritis	DISQZGBV	Strong	Genetic Variation	[22]
Lung cancer	DISCM4YA	Strong	Biomarker	[23]
Lung carcinoma	DISTR26C	Strong	Biomarker	[23]
Lung neoplasm	DISVARNB	Strong	Altered Expression	[24]
Neoplasm	DISZKGEW	Strong	Biomarker	[25]
OPTN-related open angle glaucoma	DISDR98A	Strong	Genetic Variation	[26]
Osteochondrodysplasia	DIS9SPWW	Strong	Genetic Variation	[27]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[28]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[29]
Tuberculosis	DIS2YIMD	Strong	Genetic Variation	[30]
Type-1 diabetes	DIS7HLUB	Strong	Altered Expression	[31]
Ulcerative colitis	DIS8K27O	Strong	Genetic Variation	[14]
Metastatic malignant neoplasm	DIS86UK6	moderate	Biomarker	[32]
Pulmonary tuberculosis	DIS6FLUM	moderate	Genetic Variation	[33]
Advanced cancer	DISAT1Z9	Limited	Genetic Variation	[34]
Atopic dermatitis	DISTCP41	Limited	Genetic Variation	[35]
Breast cancer	DIS7DPX1	Limited	Biomarker	[9]
Clubfoot	DISLXT4S	Limited	Biomarker	[36]
Dementia	DISXL1WY	Limited	Biomarker	[37]
Hepatitis C virus infection	DISQ0M8R	Limited	Genetic Variation	[38]
Herpes simplex infection	DISL1SAV	Limited	Genetic Variation	[39]
Melanoma	DIS1RRCY	Limited	Biomarker	[40]

21 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 Filamin-B (FLNB).	[41]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Filamin-B (FLNB).	[42]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Filamin-B (FLNB).	[43]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Filamin-B (FLNB).	[44]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Filamin-B (FLNB).	[45]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Filamin-B (FLNB).	[46]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Filamin-B (FLNB).	[47]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Filamin-B (FLNB).	[48]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Filamin-B (FLNB).	[50]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Filamin-B (FLNB).	[51]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Filamin-B (FLNB).	[52]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Filamin-B (FLNB).	[53]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Filamin-B (FLNB).	[54]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Filamin-B (FLNB).	[55]
Rofecoxib	DM3P5DA	Approved	Rofecoxib increases the expression of Filamin-B (FLNB).	[56]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Filamin-B (FLNB).	[53]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Filamin-B (FLNB).	[60]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Filamin-B (FLNB).	[62]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Filamin-B (FLNB).	[63]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Filamin-B (FLNB).	[64]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of Filamin-B (FLNB).	[65]

4 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 Filamin-B (FLNB).	[49]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Filamin-B (FLNB).	[58]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Filamin-B (FLNB).	[59]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Filamin-B (FLNB).	[61]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of Filamin-B (FLNB).	[57]

References

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