Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0OAYWT)

• DOT Name: Four and a half LIM domains protein 2 (FHL2)
• Synonyms: FHL-2; LIM domain protein DRAL; Skeletal muscle LIM-protein 3; SLIM-3
• Gene Name: FHL2
• Related Disease:
  Acute myelogenous leukaemia
  Adult glioblastoma
  Alzheimer disease
  Arteriosclerosis
  Atherosclerosis
  Breast cancer
  Breast carcinoma
  Cardiomyopathy
  Cervical cancer
  Colon cancer
  Colorectal carcinoma
  Epithelial ovarian cancer
  Familial dilated cardiomyopathy
  Glioblastoma multiforme
  Glioma
  Hepatocellular carcinoma
  Hereditary hemophagocytic lymphohistiocytosis
  Leukemia
  Matthew-Wood syndrome
  Metastatic malignant neoplasm
  Neoplasm
  Osteoarthritis
  Ovarian cancer
  Ovarian neoplasm
  Prostate cancer
  Prostate carcinoma
  Prostate neoplasm
  Rhabdomyosarcoma
  Rheumatoid arthritis
  Cardiovascular disease
  High blood pressure
  Hypertrophic cardiomyopathy
  Neuroblastoma
  Obsolete familial isolated dilated cardiomyopathy
  Carcinoma of liver and intrahepatic biliary tract
  Cervical carcinoma
  Liver cancer
  Adenoma
  Advanced cancer
  Asthma
  Bone osteosarcoma
  Breast neoplasm
  Colon carcinoma
  Osteosarcoma
  Pancreatic cancer
  Type-1/2 diabetes
  Ulcerative colitis
• UniProt ID: FHL2_HUMAN
• PDB ID: 1X4K; 1X4L; 2D8Z; 2MIU
• Pfam ID: PF00412
• Sequence:
  MTERFDCHHCNESLFGKKYILREESPYCVVCFETLFANTCEECGKPIGCDCKDLSYKDRH
  WHEACFHCSQCRNSLVDKPFAAKEDQLLCTDCYSNEYSSKCQECKKTIMPGTRKMEYKGS
  SWHETCFICHRCQQPIGTKSFIPKDNQNFCVPCYEKQHAMQCVQCKKPITTGGVTYREQP
  WHKECFVCTACRKQLSGQRFTARDDFAYCLNCFCDLYAKKCAGCTNPISGLGGTKYISFE
  ERQWHNDCFNCKKCSLSLVGRGFLTERDDILCPDCGKDI
• Function: May function as a molecular transmitter linking various signaling pathways to transcriptional regulation. Negatively regulates the transcriptional repressor E4F1 and may function in cell growth. Inhibits the transcriptional activity of FOXO1 and its apoptotic function by enhancing the interaction of FOXO1 with SIRT1 and FOXO1 deacetylation. Negatively regulates the calcineurin/NFAT signaling pathway in cardiomyocytes.
• Tissue Specificity: Expressed in skeletal muscle and heart.
• KEGG Pathway:
  Osteoclast differentiation (hsa04380)
  Cytoskeleton in muscle cells (hsa04820)
• Reactome Pathway: PPARA activates gene expression (R-HSA-1989781)

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Strong	Altered Expression	[1]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[2]
Alzheimer disease	DISF8S70	Strong	Biomarker	[3]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[4]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[5]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[5]
Cardiomyopathy	DISUPZRG	Strong	Genetic Variation	[6]
Cervical cancer	DISFSHPF	Strong	Altered Expression	[7]
Colon cancer	DISVC52G	Strong	Altered Expression	[8]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[9]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[10]
Familial dilated cardiomyopathy	DISBHDU9	Strong	GermlineCausalMutation	[11]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[2]
Glioma	DIS5RPEH	Strong	Altered Expression	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[12]
Hereditary hemophagocytic lymphohistiocytosis	DISQP21Z	Strong	Genetic Variation	[13]
Leukemia	DISNAKFL	Strong	Biomarker	[14]
Matthew-Wood syndrome	DISA7HR7	Strong	Altered Expression	[15]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[16]
Neoplasm	DISZKGEW	Strong	Altered Expression	[12]
Osteoarthritis	DIS05URM	Strong	Altered Expression	[17]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[10]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[10]
Prostate cancer	DISF190Y	Strong	Altered Expression	[5]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[5]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[18]
Rhabdomyosarcoma	DISNR7MS	Strong	Altered Expression	[19]
Rheumatoid arthritis	DISTSB4J	Strong	Altered Expression	[17]
Cardiovascular disease	DIS2IQDX	moderate	Biomarker	[20]
High blood pressure	DISY2OHH	moderate	Biomarker	[21]
Hypertrophic cardiomyopathy	DISQG2AI	moderate	Genetic Variation	[22]
Neuroblastoma	DISVZBI4	moderate	Altered Expression	[23]
Obsolete familial isolated dilated cardiomyopathy	DIS4FXO4	Supportive	Autosomal dominant	[11]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Disputed	Altered Expression	[5]
Cervical carcinoma	DIST4S00	Disputed	Altered Expression	[7]
Liver cancer	DISDE4BI	Disputed	Altered Expression	[5]
Adenoma	DIS78ZEV	Limited	Biomarker	[8]
Advanced cancer	DISAT1Z9	Limited	Altered Expression	[1]
Asthma	DISW9QNS	Limited	Biomarker	[24]
Bone osteosarcoma	DIST1004	Limited	Altered Expression	[25]
Breast neoplasm	DISNGJLM	Limited	Altered Expression	[26]
Colon carcinoma	DISJYKUO	Limited	Altered Expression	[8]
Osteosarcoma	DISLQ7E2	Limited	Altered Expression	[25]
Pancreatic cancer	DISJC981	Limited	Biomarker	[16]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[27]
Ulcerative colitis	DIS8K27O	Limited	Altered Expression	[28]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Temozolomide	DMKECZD	Approved	Four and a half LIM domains protein 2 (FHL2) affects the response to substance of Temozolomide.	[63]
Fluorouracil	DMUM7HZ	Approved	Four and a half LIM domains protein 2 (FHL2) affects the response to substance of Fluorouracil.	[64]
DTI-015	DMXZRW0	Approved	Four and a half LIM domains protein 2 (FHL2) affects the response to substance of DTI-015.	[63]

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 Four and a half LIM domains protein 2 (FHL2).	[29]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Four and a half LIM domains protein 2 (FHL2).	[45]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Four and a half LIM domains protein 2 (FHL2).	[53]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Four and a half LIM domains protein 2 (FHL2).	[45]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Four and a half LIM domains protein 2 (FHL2).	[30]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Four and a half LIM domains protein 2 (FHL2).	[31]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Four and a half LIM domains protein 2 (FHL2).	[32]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Four and a half LIM domains protein 2 (FHL2).	[33]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Four and a half LIM domains protein 2 (FHL2).	[34]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Four and a half LIM domains protein 2 (FHL2).	[35]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Four and a half LIM domains protein 2 (FHL2).	[36]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Four and a half LIM domains protein 2 (FHL2).	[37]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Four and a half LIM domains protein 2 (FHL2).	[38]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Four and a half LIM domains protein 2 (FHL2).	[39]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Four and a half LIM domains protein 2 (FHL2).	[39]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Four and a half LIM domains protein 2 (FHL2).	[40]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Four and a half LIM domains protein 2 (FHL2).	[41]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Four and a half LIM domains protein 2 (FHL2).	[42]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Four and a half LIM domains protein 2 (FHL2).	[43]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Four and a half LIM domains protein 2 (FHL2).	[44]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Four and a half LIM domains protein 2 (FHL2).	[38]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Four and a half LIM domains protein 2 (FHL2).	[46]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Four and a half LIM domains protein 2 (FHL2).	[47]
Etoposide	DMNH3PG	Approved	Etoposide decreases the expression of Four and a half LIM domains protein 2 (FHL2).	[48]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol affects the expression of Four and a half LIM domains protein 2 (FHL2).	[49]
Sulindac	DM2QHZU	Approved	Sulindac increases the expression of Four and a half LIM domains protein 2 (FHL2).	[50]
Estrone	DM5T6US	Approved	Estrone increases the expression of Four and a half LIM domains protein 2 (FHL2).	[51]
Mestranol	DMG3F94	Approved	Mestranol increases the expression of Four and a half LIM domains protein 2 (FHL2).	[51]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Four and a half LIM domains protein 2 (FHL2).	[52]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Four and a half LIM domains protein 2 (FHL2).	[54]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Four and a half LIM domains protein 2 (FHL2).	[55]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Four and a half LIM domains protein 2 (FHL2).	[56]
HEXESTROL	DM9AGWQ	Withdrawn from market	HEXESTROL increases the expression of Four and a half LIM domains protein 2 (FHL2).	[51]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Four and a half LIM domains protein 2 (FHL2).	[57]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Four and a half LIM domains protein 2 (FHL2).	[58]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Four and a half LIM domains protein 2 (FHL2).	[59]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Four and a half LIM domains protein 2 (FHL2).	[60]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Four and a half LIM domains protein 2 (FHL2).	[61]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Four and a half LIM domains protein 2 (FHL2).	[62]

References

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