General Information of Drug Off-Target (DOT) (ID: OTRT3F3U)

DOT Name 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR)
Synonyms HMG-CoA reductase; EC 1.1.1.34
Gene Name HMGCR
Related Disease
Muscular dystrophy, limb-girdle, autosomal recessive 28 ( )
UniProt ID
HMDH_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
1DQ8; 1DQ9; 1DQA; 1HW8; 1HW9; 1HWI; 1HWJ; 1HWK; 1HWL; 2Q1L; 2Q6B; 2Q6C; 2R4F; 3BGL; 3CCT; 3CCW; 3CCZ; 3CD0; 3CD5; 3CD7; 3CDA; 3CDB
EC Number
1.1.1.34
Pfam ID
PF00368 ; PF12349
Sequence
MLSRLFRMHGLFVASHPWEVIVGTVTLTICMMSMNMFTGNNKICGWNYECPKFEEDVLSS
DIIILTITRCIAILYIYFQFQNLRQLGSKYILGIAGLFTIFSSFVFSTVVIHFLDKELTG
LNEALPFFLLLIDLSRASTLAKFALSSNSQDEVRENIARGMAILGPTFTLDALVECLVIG
VGTMSGVRQLEIMCCFGCMSVLANYFVFMTFFPACVSLVLELSRESREGRPIWQLSHFAR
VLEEEENKPNPVTQRVKMIMSLGLVLVHAHSRWIADPSPQNSTADTSKVSLGLDENVSKR
IEPSVSLWQFYLSKMISMDIEQVITLSLALLLAVKYIFFEQTETESTLSLKNPITSPVVT
QKKVPDNCCRREPMLVRNNQKCDSVEEETGINRERKVEVIKPLVAETDTPNRATFVVGNS
SLLDTSSVLVTQEPEIELPREPRPNEECLQILGNAEKGAKFLSDAEIIQLVNAKHIPAYK
LETLMETHERGVSIRRQLLSKKLSEPSSLQYLPYRDYNYSLVMGACCENVIGYMPIPVGV
AGPLCLDEKEFQVPMATTEGCLVASTNRGCRAIGLGGGASSRVLADGMTRGPVVRLPRAC
DSAEVKAWLETSEGFAVIKEAFDSTSRFARLQKLHTSIAGRNLYIRFQSRSGDAMGMNMI
SKGTEKALSKLHEYFPEMQILAVSGNYCTDKKPAAINWIEGRGKSVVCEAVIPAKVVREV
LKTTTEAMIEVNINKNLVGSAMAGSIGGYNAHAANIVTAIYIACGQDAAQNVGSSNCITL
MEASGPTNEDLYISCTMPSIEIGTVGGGTNLLPQQACLQMLGVQGACKDNPGENARQLAR
IVCGTVMAGELSLMAALAAGHLVKSHMIHNRSKINLQDLQGACTKKTA
Function
Catalyzes the conversion of (3S)-hydroxy-3-methylglutaryl-CoA (HMG-CoA) to mevalonic acid, the rate-limiting step in the synthesis of cholesterol and other isoprenoids, thus plays a critical role in cellular cholesterol homeostasis. HMGCR is the main target of statins, a class of cholesterol-lowering drugs.
Tissue Specificity
.Ubiquitously expressed with the highest levels in the cerebellum, fetal brain, testis, skin and adrenal gland.; [Isoform 2]: Detected in the cerebellum, fetal brain, testis and adrenal gland.; [Isoform 3]: Low abundance except in skin, esophagus, and uterine cervix.
KEGG Pathway
Terpenoid backbone biosynthesis (hsa00900 )
Metabolic pathways (hsa01100 )
AMPK sig.ling pathway (hsa04152 )
Bile secretion (hsa04976 )
Reactome Pathway
EGR2 and SOX10-mediated initiation of Schwann cell myelination (R-HSA-9619665 )
Cholesterol biosynthesis (R-HSA-191273 )
BioCyc Pathway
MetaCyc:HS03652-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Muscular dystrophy, limb-girdle, autosomal recessive 28 DISNMUMC Strong Autosomal recessive [1]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 6 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Estradiol DMUNTE3 Approved 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) increases the Lipid metabolism disorder ADR of Estradiol. [65]
Simvastatin DM30SGU Approved 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) decreases the response to substance of Simvastatin. [66]
Chenodiol DMQ8JIK Approved 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) decreases the response to substance of Chenodiol. [67]
Digoxin DMQCTIH Approved 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) increases the Iron and trace metal metabolism disorders ADR of Digoxin. [65]
Pravastatin DM6A0X7 Approved 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) increases the LDL cholesterol increased ADR of Pravastatin. [68]
Rosuvastatin DMMIQ7G Approved 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) increases the LDL cholesterol increased ADR of Rosuvastatin. [68]
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⏷ Show the Full List of 6 Drug(s)
This DOT Affected the Regulation of Drug Effects of 1 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Geranyl Diphosphate DMB9LE1 Investigative 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) increases the abundance of Geranyl Diphosphate. [69]
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2 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 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [2]
Arsenic DMTL2Y1 Approved Arsenic decreases the ubiquitination of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [8]
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74 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 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [3]
Tretinoin DM49DUI Approved Tretinoin increases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [4]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [5]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [6]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [7]
Quercetin DM3NC4M Approved Quercetin decreases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [9]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide increases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [10]
Testosterone DM7HUNW Approved Testosterone decreases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [11]
Carbamazepine DMZOLBI Approved Carbamazepine decreases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [12]
Decitabine DMQL8XJ Approved Decitabine affects the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [13]
Progesterone DMUY35B Approved Progesterone increases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [14]
Menadione DMSJDTY Approved Menadione increases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [10]
Isotretinoin DM4QTBN Approved Isotretinoin decreases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [15]
Troglitazone DM3VFPD Approved Troglitazone increases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [16]
Azathioprine DMMZSXQ Approved Azathioprine decreases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [17]
Ethanol DMDRQZU Approved Ethanol decreases the activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [18]
Nicotine DMWX5CO Approved Nicotine increases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [19]
Piroxicam DMTK234 Approved Piroxicam decreases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [20]
Clozapine DMFC71L Approved Clozapine increases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [21]
Obeticholic acid DM3Q1SM Approved Obeticholic acid decreases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [22]
Pioglitazone DMKJ485 Approved Pioglitazone increases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [16]
Haloperidol DM96SE0 Approved Haloperidol increases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [21]
Hydrocortisone DMGEMB7 Approved Hydrocortisone decreases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [23]
Fluoxetine DM3PD2C Approved Fluoxetine increases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [24]
Lovastatin DM9OZWQ Approved Lovastatin increases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [25]
Bezafibrate DMZDCS0 Approved Bezafibrate increases the activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [26]
Olanzapine DMPFN6Y Approved Olanzapine increases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [27]
Crizotinib DM4F29C Approved Crizotinib increases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [28]
Methimazole DM25FL8 Approved Methimazole decreases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [29]
Clofibrate DMPC1J7 Approved Clofibrate decreases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [30]
Hydroxychloroquine DMSIVND Approved Hydroxychloroquine affects the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [31]
Risperidone DMN6DXL Approved Risperidone increases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [27]
Ezetimibe DM7A8TW Approved Ezetimibe increases the activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [32]
Ziprasidone DMM58JY Approved Ziprasidone increases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [27]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [33]
Dihydrotestosterone DM3S8XC Phase 4 Dihydrotestosterone increases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [34]
SNDX-275 DMH7W9X Phase 3 SNDX-275 decreases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [35]
Resveratrol DM3RWXL Phase 3 Resveratrol decreases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [36]
Epigallocatechin gallate DMCGWBJ Phase 3 Epigallocatechin gallate increases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [37]
Curcumin DMQPH29 Phase 3 Curcumin increases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [38]
Chlorpromazine DMBGZI3 Phase 3 Trial Chlorpromazine increases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [27]
Atorvastatin DMF28YC Phase 3 Trial Atorvastatin increases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [39]
GSK2110183 DMZHB37 Phase 2 GSK2110183 increases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [40]
phorbol 12-myristate 13-acetate DMJWD62 Phase 2 phorbol 12-myristate 13-acetate increases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [16]
ANW-32821 DMMJOZD Phase 2 ANW-32821 decreases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [41]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [42]
GSK618334 DMJPXZ4 Phase 1 GSK618334 increases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [43]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [44]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 increases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [45]
THAPSIGARGIN DMDMQIE Preclinical THAPSIGARGIN decreases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [46]
Bisphenol A DM2ZLD7 Investigative Bisphenol A affects the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [47]
Trichostatin A DM9C8NX Investigative Trichostatin A affects the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [48]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [49]
Nickel chloride DMI12Y8 Investigative Nickel chloride decreases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [50]
geraniol DMS3CBD Investigative geraniol decreases the activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [51]
[3H]methyltrienolone DMTSGOW Investigative [3H]methyltrienolone increases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [52]
OXYQUINOLINE DMZVS9Y Investigative OXYQUINOLINE decreases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [9]
Forskolin DM6ITNG Investigative Forskolin increases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [52]
Okadaic acid DM47CO1 Investigative Okadaic acid decreases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [53]
Rapamycin Immunosuppressant Drug DM678IB Investigative Rapamycin Immunosuppressant Drug increases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [41]
Arachidonic acid DMUOQZD Investigative Arachidonic acid decreases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [54]
PP-242 DM2348V Investigative PP-242 decreases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [55]
OXYBENZONE DMMZYX6 Investigative OXYBENZONE increases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [56]
Linalool DMGZQ5P Investigative Linalool decreases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [57]
Farnesol DMV2X1B Investigative Farnesol decreases the activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [51]
27-hydroxycholesterol DM2L6OZ Investigative 27-hydroxycholesterol decreases the activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [58]
BETULIN DMGQRON Investigative BETULIN decreases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [59]
Ganoderic acid A DM42EVG Investigative Ganoderic acid A decreases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [60]
25-hydroxycholesterol DMCHAQ7 Investigative 25-hydroxycholesterol decreases the activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [58]
eucalyptol DME5CK3 Investigative eucalyptol decreases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [61]
24(S)-hydroxycholesterol DMGMWA6 Investigative 24(S)-hydroxycholesterol decreases the activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [62]
NADA DM3ORGM Investigative NADA decreases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [63]
PF-429242 DMB0OZ3 Investigative PF-429242 decreases the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [59]
Dihydrolanosterol DMG0PXI Investigative Dihydrolanosterol decreases the activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). [64]
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⏷ Show the Full List of 74 Drug(s)

References

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