Details of Drug Off-Target (DOT)

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

• DOT Name: Sterol regulatory element-binding protein 1 (SREBF1)
• Synonyms: SREBP-1; Class D basic helix-loop-helix protein 1; bHLHd1; Sterol regulatory element-binding transcription factor 1
• Gene Name: SREBF1
• Related Disease:
  Hereditary mucoepithelial dysplasia
  IFAP syndrome 2
  Hirschsprung disease
• UniProt ID: SRBP1_HUMAN
• PDB ID: 1AM9
• Pfam ID: PF00010
• Sequence:
  MDEPPFSEAALEQALGEPCDLDAALLTDIEDMLQLINNQDSDFPGLFDPPYAGSGAGGTD
  PASPDTSSPGSLSPPPATLSSSLEAFLSGPQAAPSPLSPPQPAPTPLKMYPSMPAFSPGP
  GIKEESVPLSILQTPTPQPLPGALLPQSFPAPAPPQFSSTPVLGYPSPPGGFSTGSPPGN
  TQQPLPGLPLASPPGVPPVSLHTQVQSVVPQQLLTVTAAPTAAPVTTTVTSQIQQVPVLL
  QPHFIKADSLLLTAMKTDGATVKAAGLSPLVSGTTVQTGPLPTLVSGGTILATVPLVVDA
  EKLPINRLAAGSKAPASAQSRGEKRTAHNAIEKRYRSSINDKIIELKDLVVGTEAKLNKS
  AVLRKAIDYIRFLQHSNQKLKQENLSLRTAVHKSKSLKDLVSACGSGGNTDVLMEGVKTE
  VEDTLTPPPSDAGSPFQSSPLSLGSRGSGSGGSGSDSEPDSPVFEDSKAKPEQRPSLHSR
  GMLDRSRLALCTLVFLCLSCNPLASLLGARGLPSPSDTTSVYHSPGRNVLGTESRDGPGW
  AQWLLPPVVWLLNGLLVLVSLVLLFVYGEPVTRPHSGPAVYFWRHRKQADLDLARGDFAQ
  AAQQLWLALRALGRPLPTSHLDLACSLLWNLIRHLLQRLWVGRWLAGRAGGLQQDCALRV
  DASASARDAALVYHKLHQLHTMGKHTGGHLTATNLALSALNLAECAGDAVSVATLAEIYV
  AAALRVKTSLPRALHFLTRFFLSSARQACLAQSGSVPPAMQWLCHPVGHRFFVDGDWSVL
  STPWESLYSLAGNPVDPLAQVTQLFREHLLERALNCVTQPNPSPGSADGDKEFSDALGYL
  QLLNSCSDAAGAPAYSFSISSSMATTTGVDPVAKWWASLTAVVIHWLRRDEEAAERLCPL
  VEHLPRVLQESERPLPRAALHSFKAARALLGCAKAESGPASLTICEKASGYLQDSLATTP
  ASSSIDKAVQLFLCDLLLVVRTSLWRQQQPPAPAPAAQGTSSRPQASALELRGFQRDLSS
  LRRLAQSFRPAMRRVFLHEATARLMAGASPTRTHQLLDRSLRRRAGPGGKGGAVAELEPR
  PTRREHAEALLLASCYLPPGFLSAPGQRVGMLAEAARTLEKLGDRRLLHDCQQMLMRLGG
  GTTVTSS
• Function: [Sterol regulatory element-binding protein 1]: Precursor of the transcription factor form (Processed sterol regulatory element-binding protein 1), which is embedded in the endoplasmic reticulum membrane. Low sterol concentrations promote processing of this form, releasing the transcription factor form that translocates into the nucleus and activates transcription of genes involved in cholesterol biosynthesis and lipid homeostasis; [Processed sterol regulatory element-binding protein 1]: Key transcription factor that regulates expression of genes involved in cholesterol biosynthesis and lipid homeostasis. Binds to the sterol regulatory element 1 (SRE-1) (5'-ATCACCCCAC-3'). Has dual sequence specificity binding to both an E-box motif (5'-ATCACGTGA-3') and to SRE-1 (5'-ATCACCCCAC-3'). Regulates the promoters of genes involved in cholesterol biosynthesis and the LDL receptor (LDLR) pathway of sterol regulation ; [Isoform SREBP-1A]: Isoform expressed only in select tissues, which has higher transcriptional activity compared to SREBP-1C. Able to stimulate both lipogenic and cholesterogenic gene expression. Has a role in the nutritional regulation of fatty acids and triglycerides in lipogenic organs such as the liver. Required for innate immune response in macrophages by regulating lipid metabolism; [Isoform SREBP-1C]: Predominant isoform expressed in most tissues, which has weaker transcriptional activity compared to isoform SREBP-1A. Primarily controls expression of lipogenic gene. Strongly activates global lipid synthesis in rapidly growing cells; [Isoform SREBP-1aDelta]: The absence of Golgi proteolytic processing requirement makes this isoform constitutively active in transactivation of lipogenic gene promoters; [Isoform SREBP-1cDelta]: The absence of Golgi proteolytic processing requirement makes this isoform constitutively active in transactivation of lipogenic gene promoters.
• Tissue Specificity: Expressed in a wide variety of tissues, most abundant in liver and adrenal gland . In fetal tissues lung and liver shows highest expression .; [Isoform SREBP-1A]: Predominates in hepatoma cell lines . Also expressed in kidney, brain, white fat, and muscle .; [Isoform SREBP-1C]: Predominantly expressed in liver and adipose tissues . Also expressed in kidney, brain, white fat, and muscle .
• KEGG Pathway:
  AMPK sig.ling pathway (hsa04152)
  Insulin sig.ling pathway (hsa04910)
  Insulin resistance (hsa04931)
  Non-alcoholic fatty liver disease (hsa04932)
  Alcoholic liver disease (hsa04936)
• Reactome Pathway:
  Regulation of cholesterol biosynthesis by SREBP (SREBF) (R-HSA-1655829)
  Cholesterol biosynthesis (R-HSA-191273)
  PPARA activates gene expression (R-HSA-1989781)
  Activation of gene expression by SREBF (SREBP) (R-HSA-2426168)
  FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes (R-HSA-9615017)
  RORA activates gene expression (R-HSA-1368082)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hereditary mucoepithelial dysplasia	DISCSNIE	Strong	Autosomal dominant	[1]
IFAP syndrome 2	DISIL237	Strong	Autosomal dominant	[1]
Hirschsprung disease	DISUUSM1	Supportive	Autosomal dominant	[2]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Ritonavir	DMU764S	Approved	Sterol regulatory element-binding protein 1 (SREBF1) increases the Hepatomegaly ADR of Ritonavir.	[72]

77 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 Sterol regulatory element-binding protein 1 (SREBF1).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[8]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[9]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[10]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[11]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[12]
Phenobarbital	DMXZOCG	Approved	Phenobarbital decreases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[13]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil affects the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[14]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[15]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[16]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[17]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[18]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[19]
Nicotine	DMWX5CO	Approved	Nicotine decreases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[20]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[21]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[22]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid decreases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[24]
Capsaicin	DMGMF6V	Approved	Capsaicin increases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[25]
Lindane	DMB8CNL	Approved	Lindane increases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[26]
Hydrocortisone	DMGEMB7	Approved	Hydrocortisone increases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[27]
Beta-carotene	DM0RXBT	Approved	Beta-carotene increases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[28]
Bexarotene	DMOBIKY	Approved	Bexarotene increases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[29]
Chenodiol	DMQ8JIK	Approved	Chenodiol decreases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[30]
Lovastatin	DM9OZWQ	Approved	Lovastatin increases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[31]
Orlistat	DMRJSP8	Approved	Orlistat decreases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[32]
Eicosapentaenoic acid/docosa-hexaenoic acid	DMMUCG4	Approved	Eicosapentaenoic acid/docosa-hexaenoic acid decreases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[33]
Tetracycline	DMZA017	Approved	Tetracycline increases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[34]
Romidepsin	DMT5GNL	Approved	Romidepsin increases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[35]
Nevirapine	DM6HX9B	Approved	Nevirapine increases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[36]
Clavulanate	DM2FGRT	Approved	Clavulanate decreases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[37]
Clofibrate	DMPC1J7	Approved	Clofibrate increases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[34]
Efavirenz	DMC0GSJ	Approved	Efavirenz decreases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[36]
Vemurafenib	DM62UG5	Approved	Vemurafenib decreases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[39]
Ezetimibe	DM7A8TW	Approved	Ezetimibe decreases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[40]
OPC-34712	DMHG57U	Approved	OPC-34712 decreases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[41]
AZD5363	DM9SKW8	Approved	AZD5363 decreases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[42]
Tianeptine	DMYN8MA	Approved	Tianeptine increases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[34]
Ketotifen	DM74XKS	Approved	Ketotifen increases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[34]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[43]
Berberine	DMC5Q8X	Phase 4	Berberine decreases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[44]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[45]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[27]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[46]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[47]
AZD4547	DM3827C	Phase 2/3	AZD4547 decreases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[42]
Azd2014	DMOEARH	Phase 2	Azd2014 decreases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[42]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[49]
LY294002	DMY1AFS	Phase 1	LY294002 decreases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[50]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[51]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[16]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[54]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[55]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid increases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[56]
D-glucose	DMMG2TO	Investigative	D-glucose increases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[57]
Tributylstannanyl	DMHN7CB	Investigative	Tributylstannanyl increases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[58]
U0126	DM31OGF	Investigative	U0126 decreases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[59]
Dibutyl phthalate	DMEDGKO	Investigative	Dibutyl phthalate increases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[60]
Cordycepin	DM72Y01	Investigative	Cordycepin decreases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[61]
Lead acetate	DML0GZ2	Investigative	Lead acetate increases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[62]
Oleic acid	DM54O1Z	Investigative	Oleic acid decreases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[33]
GW-3965	DMG60ET	Investigative	GW-3965 increases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[63]
T0901317	DMZQVDI	Investigative	T0901317 increases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[64]
Icosapentum	DMF1CM7	Investigative	Icosapentum decreases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[33]
L-Serine	DM6WPIS	Investigative	L-Serine decreases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[65]
CITCO	DM0N634	Investigative	CITCO decreases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[13]
NMS-873	DMYKZ6U	Investigative	NMS-873 decreases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[66]
Ganoderic acid A	DM42EVG	Investigative	Ganoderic acid A decreases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[67]
Ginsenoside Re	DM46FVD	Investigative	Ginsenoside Re decreases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[68]
AMENTOFLAVONE	DMLRNV2	Investigative	AMENTOFLAVONE decreases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[69]
NADA	DM3ORGM	Investigative	NADA decreases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[59]
paxilline	DMPF2N1	Investigative	paxilline increases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[29]
Raffinose	DMVHDOS	Investigative	Raffinose decreases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[71]
CD3254	DM38MU1	Investigative	CD3254 increases the expression of Sterol regulatory element-binding protein 1 (SREBF1).	[29]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Simvastatin	DM30SGU	Approved	Simvastatin increases the localization of Sterol regulatory element-binding protein 1 (SREBF1).	[23]
Nelfinavir mesylate	DMFX6G8	Approved	Nelfinavir mesylate decreases the cleavage of Sterol regulatory element-binding protein 1 (SREBF1).	[38]
Dabrafenib	DMX6OE3	Approved	Dabrafenib decreases the cleavage of Sterol regulatory element-binding protein 1 (SREBF1).	[39]
BETULIN	DMGQRON	Investigative	BETULIN decreases the cleavage of Sterol regulatory element-binding protein 1 (SREBF1).	[39]
PF-429242	DMB0OZ3	Investigative	PF-429242 decreases the cleavage of Sterol regulatory element-binding protein 1 (SREBF1).	[70]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Sterol regulatory element-binding protein 1 (SREBF1).	[48]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Sterol regulatory element-binding protein 1 (SREBF1).	[52]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Sterol regulatory element-binding protein 1 (SREBF1).	[53]

References

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