Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEZUR1L)

• DOT Name: Caveolin-1 (CAV1)
• Gene Name: CAV1
• Related Disease:
  Pulmonary arterial hypertension
  Partial lipodystrophy, congenital cataracts, and neurodegeneration syndrome
  Pulmonary hypertension, primary, 3
  Congenital generalized lipodystrophy type 3
  Berardinelli-Seip congenital lipodystrophy
  Heritable pulmonary arterial hypertension
  Amyotrophic lateral sclerosis
• UniProt ID: CAV1_HUMAN
• PDB ID: 7SC0
• Pfam ID: PF01146
• Sequence:
  MSGGKYVDSEGHLYTVPIREQGNIYKPNNKAMADELSEKQVYDAHTKEIDLVNRDPKHLN
  DDVVKIDFEDVIAEPEGTHSFDGIWKASFTTFTVTKYWFYRLLSALFGIPMALIWGIYFA
  ILSFLHIWAVVPCIKSFLIEIQCISRVYSIYVHTVCDPLFEAVGKIFSNVRINLQKEI
• Function: May act as a scaffolding protein within caveolar membranes. Forms a stable heterooligomeric complex with CAV2 that targets to lipid rafts and drives caveolae formation. Mediates the recruitment of CAVIN proteins (CAVIN1/2/3/4) to the caveolae. Interacts directly with G-protein alpha subunits and can functionally regulate their activity. Involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation. Its binding to DPP4 induces T-cell proliferation and NF-kappa-B activation in a T-cell receptor/CD3-dependent manner. Recruits CTNNB1 to caveolar membranes and may regulate CTNNB1-mediated signaling through the Wnt pathway. Negatively regulates TGFB1-mediated activation of SMAD2/3 by mediating the internalization of TGFBR1 from membrane rafts leading to its subsequent degradation. Binds 20(S)-hydroxycholesterol (20(S)-OHC).
• Tissue Specificity: Skeletal muscle, liver, stomach, lung, kidney and heart (at protein level). Expressed in the brain.
• KEGG Pathway:
  Endocytosis (hsa04144)
  Focal adhesion (hsa04510)
  Prion disease (hsa05020)
  Bacterial invasion of epithelial cells (hsa05100)
  Proteoglycans in cancer (hsa05205)
  Viral myocarditis (hsa05416)
  Fluid shear stress and atherosclerosis (hsa05418)
• Reactome Pathway:
  eNOS activation (R-HSA-203615)
  NOSTRIN mediated eNOS trafficking (R-HSA-203641)
  Basigin interactions (R-HSA-210991)
  Disassembly of the destruction complex and recruitment of AXIN to the membrane (R-HSA-4641262)
  VEGFR2 mediated vascular permeability (R-HSA-5218920)
  RHOA GTPase cycle (R-HSA-8980692)
  Extra-nuclear estrogen signaling (R-HSA-9009391)
  RHOB GTPase cycle (R-HSA-9013026)
  RHOC GTPase cycle (R-HSA-9013106)
  CDC42 GTPase cycle (R-HSA-9013148)
  RAC1 GTPase cycle (R-HSA-9013149)
  RAC2 GTPase cycle (R-HSA-9013404)
  RHOD GTPase cycle (R-HSA-9013405)
  RHOQ GTPase cycle (R-HSA-9013406)
  RHOH GTPase cycle (R-HSA-9013407)
  RHOG GTPase cycle (R-HSA-9013408)
  RHOJ GTPase cycle (R-HSA-9013409)
  RAC3 GTPase cycle (R-HSA-9013423)
  RHOF GTPase cycle (R-HSA-9035034)
  FOXO-mediated transcription of cell cycle genes (R-HSA-9617828)
  RND3 GTPase cycle (R-HSA-9696264)
  RND2 GTPase cycle (R-HSA-9696270)
  RND1 GTPase cycle (R-HSA-9696273)
  SARS-CoV-1 targets host intracellular signalling and regulatory pathways (R-HSA-9735871)
  SARS-CoV-2 targets host intracellular signalling and regulatory pathways (R-HSA-9755779)
  Triglyceride catabolism (R-HSA-163560)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Pulmonary arterial hypertension	DISP8ZX5	Definitive	Autosomal dominant	[1]
Partial lipodystrophy, congenital cataracts, and neurodegeneration syndrome	DISWL6YJ	Strong	Autosomal dominant	[2]
Pulmonary hypertension, primary, 3	DIS1J9D4	Strong	Autosomal dominant	[3]
Congenital generalized lipodystrophy type 3	DISB5MJI	Moderate	Autosomal dominant	[4]
Berardinelli-Seip congenital lipodystrophy	DISKW75N	Supportive	Autosomal recessive	[3]
Heritable pulmonary arterial hypertension	DISD1Y94	Supportive	Autosomal dominant	[5]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Autosomal dominant	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Caveolin-1 (CAV1) affects the response to substance of Doxorubicin.	[51]
Cisplatin	DMRHGI9	Approved	Caveolin-1 (CAV1) increases the response to substance of Cisplatin.	[52]
Methotrexate	DM2TEOL	Approved	Caveolin-1 (CAV1) decreases the response to substance of Methotrexate.	[53]
Paclitaxel	DMLB81S	Approved	Caveolin-1 (CAV1) increases the response to substance of Paclitaxel.	[54]
Resveratrol	DM3RWXL	Phase 3	Caveolin-1 (CAV1) increases the response to substance of Resveratrol.	[55]

This DOT Affected the Regulation of Drug Effects of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
ANW-32821	DMMJOZD	Phase 2	Caveolin-1 (CAV1) increases the transport of ANW-32821.	[56]
Taurocholic acid	DM2LZ8F	Phase 1/2	Caveolin-1 (CAV1) increases the secretion of Taurocholic acid.	[57]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Caveolin-1 (CAV1).	[6]
Camptothecin	DM6CHNJ	Phase 3	Camptothecin decreases the methylation of Caveolin-1 (CAV1).	[33]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid decreases the phosphorylation of Caveolin-1 (CAV1).	[46]
2-Methylamino-succinic acid(NMDA)	DMKP6BM	Investigative	2-Methylamino-succinic acid(NMDA) increases the phosphorylation of Caveolin-1 (CAV1).	[50]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Caveolin-1 (CAV1).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Caveolin-1 (CAV1).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Caveolin-1 (CAV1).	[9]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Caveolin-1 (CAV1).	[10]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Caveolin-1 (CAV1).	[11]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Caveolin-1 (CAV1).	[12]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Caveolin-1 (CAV1).	[13]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Caveolin-1 (CAV1).	[14]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Caveolin-1 (CAV1).	[15]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Caveolin-1 (CAV1).	[16]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Caveolin-1 (CAV1).	[17]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Caveolin-1 (CAV1).	[18]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Caveolin-1 (CAV1).	[19]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Caveolin-1 (CAV1).	[20]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Caveolin-1 (CAV1).	[21]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Caveolin-1 (CAV1).	[22]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Caveolin-1 (CAV1).	[23]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Caveolin-1 (CAV1).	[24]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Caveolin-1 (CAV1).	[25]
Menthol	DMG2KW7	Approved	Menthol increases the expression of Caveolin-1 (CAV1).	[26]
Fenofibrate	DMFKXDY	Approved	Fenofibrate increases the expression of Caveolin-1 (CAV1).	[23]
Pioglitazone	DMKJ485	Approved	Pioglitazone affects the expression of Caveolin-1 (CAV1).	[27]
Acocantherin	DM7JT24	Approved	Acocantherin decreases the expression of Caveolin-1 (CAV1).	[28]
Gefitinib	DM15F0X	Approved	Gefitinib increases the expression of Caveolin-1 (CAV1).	[29]
Beta-carotene	DM0RXBT	Approved	Beta-carotene decreases the expression of Caveolin-1 (CAV1).	[30]
Nitric Oxide	DM1RBYG	Approved	Nitric Oxide increases the expression of Caveolin-1 (CAV1).	[31]
Ciprofloxacin XR	DM2NLS9	Approved	Ciprofloxacin XR increases the expression of Caveolin-1 (CAV1).	[32]
Clofibrate	DMPC1J7	Approved	Clofibrate affects the expression of Caveolin-1 (CAV1).	[27]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Caveolin-1 (CAV1).	[34]
PEITC	DMOMN31	Phase 2	PEITC decreases the expression of Caveolin-1 (CAV1).	[35]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Caveolin-1 (CAV1).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Caveolin-1 (CAV1).	[36]
Aminoguanidine	DMJQDUC	Phase 1	Aminoguanidine decreases the expression of Caveolin-1 (CAV1).	[31]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the expression of Caveolin-1 (CAV1).	[37]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 increases the expression of Caveolin-1 (CAV1).	[38]
PMID26394986-Compound-22	DM43Z1G	Patented	PMID26394986-Compound-22 increases the expression of Caveolin-1 (CAV1).	[39]
MG-132	DMKA2YS	Preclinical	MG-132 decreases the expression of Caveolin-1 (CAV1).	[31]
Scriptaid	DM9JZ21	Preclinical	Scriptaid affects the expression of Caveolin-1 (CAV1).	[40]
Nimesulide	DMR1NMD	Terminated	Nimesulide increases the expression of Caveolin-1 (CAV1).	[39]
NS398	DMINUWH	Terminated	NS398 decreases the expression of Caveolin-1 (CAV1).	[39]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Caveolin-1 (CAV1).	[41]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Caveolin-1 (CAV1).	[42]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Caveolin-1 (CAV1).	[43]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Caveolin-1 (CAV1).	[44]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Caveolin-1 (CAV1).	[45]
D-glucose	DMMG2TO	Investigative	D-glucose decreases the expression of Caveolin-1 (CAV1).	[47]
Nitrobenzanthrone	DMN6L70	Investigative	Nitrobenzanthrone increases the expression of Caveolin-1 (CAV1).	[48]
Lysophosphatidylcholine	DMOGFVH	Investigative	Lysophosphatidylcholine increases the expression of Caveolin-1 (CAV1).	[49]
CI-1040	DMF3DZX	Investigative	CI-1040 increases the expression of Caveolin-1 (CAV1).	[29]

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