Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTPADOQ)

• DTT Name: HMG-CoA reductase (HMGCR)
• Synonyms: 3-hydroxy-3-methylglutaryl-coenzyme A reductase
• Gene Name: HMGCR
• DTT Type: Successful target; [1]
• Related Disease:
  Cardiovascular disease [ICD-11: BA00-BE2Z]
  Dyslipidemia [ICD-11: 5C80-5C81]
  Hyper-lipoproteinaemia [ICD-11: 5C80]
  Multiple sclerosis [ICD-11: 8A40]
  Myocardial infarction [ICD-11: BA41-BA43]
  Pain [ICD-11: MG30-MG3Z]
  Coronary atherosclerosis [ICD-11: BA80]
• BioChemical Class: CH-OH donor oxidoreductase
• UniProt ID: HMDH_HUMAN
• TTD ID: T53585
• EC Number: EC 1.1.1.34
• Sequence:
  MLSRLFRMHGLFVASHPWEVIVGTVTLTICMMSMNMFTGNNKICGWNYECPKFEEDVLSS
  DIIILTITRCIAILYIYFQFQNLRQLGSKYILGIAGLFTIFSSFVFSTVVIHFLDKELTG
  LNEALPFFLLLIDLSRASTLAKFALSSNSQDEVRENIARGMAILGPTFTLDALVECLVIG
  VGTMSGVRQLEIMCCFGCMSVLANYFVFMTFFPACVSLVLELSRESREGRPIWQLSHFAR
  VLEEEENKPNPVTQRVKMIMSLGLVLVHAHSRWIADPSPQNSTADTSKVSLGLDENVSKR
  IEPSVSLWQFYLSKMISMDIEQVITLSLALLLAVKYIFFEQTETESTLSLKNPITSPVVT
  QKKVPDNCCRREPMLVRNNQKCDSVEEETGINRERKVEVIKPLVAETDTPNRATFVVGNS
  SLLDTSSVLVTQEPEIELPREPRPNEECLQILGNAEKGAKFLSDAEIIQLVNAKHIPAYK
  LETLMETHERGVSIRRQLLSKKLSEPSSLQYLPYRDYNYSLVMGACCENVIGYMPIPVGV
  AGPLCLDEKEFQVPMATTEGCLVASTNRGCRAIGLGGGASSRVLADGMTRGPVVRLPRAC
  DSAEVKAWLETSEGFAVIKEAFDSTSRFARLQKLHTSIAGRNLYIRFQSRSGDAMGMNMI
  SKGTEKALSKLHEYFPEMQILAVSGNYCTDKKPAAINWIEGRGKSVVCEAVIPAKVVREV
  LKTTTEAMIEVNINKNLVGSAMAGSIGGYNAHAANIVTAIYIACGQDAAQNVGSSNCITL
  MEASGPTNEDLYISCTMPSIEIGTVGGGTNLLPQQACLQMLGVQGACKDNPGENARQLAR
  IVCGTVMAGELSLMAALAAGHLVKSHMIHNRSKINLQDLQGACTKKTA
• Function: Transmembrane glycoprotein that is the rate-limiting enzyme in cholesterol biosynthesis as well as in the biosynthesis of nonsterol isoprenoids that are essential for normal cell function including ubiquinone and geranylgeranyl proteins.
• KEGG Pathway:
  Terpenoid backbone biosynthesis (hsa00900)
  Metabolic pathways (hsa01100)
  Biosynthesis of antibiotics (hsa01130)
  AMPK signaling pathway (hsa04152)
  Bile secretion (hsa04976)
• Reactome Pathway:
  PPARA activates gene expression (R-HSA-1989781)
  Activation of gene expression by SREBF (SREBP) (R-HSA-2426168)
  EGR2 and SOX10-mediated initiation of Schwann cell myelination (R-HSA-9619665)
  Cholesterol biosynthesis (R-HSA-191273)
• BioCyc Pathway: MetaCyc:HS03652-MON

Molecular Interaction Atlas (MIA) of This DTT

13 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Aspirin	DM672AH	Myocardial infarction	BA41-BA43	Approved	[1]
Atorvastatin	DMF28YC	Cardiovascular disease	BA00-BE2Z	Approved	[2]
Cerivastatin	DMXCM7H	Hyperlipidaemia	5C80	Approved	[3], [4], [5]
Crestor/TriLipix	DMJ7IQX	Dyslipidemia	5C80-5C81	Approved	[6]
Fluvastatin	DM4MDJY	Hypercholesterolaemia	5C80.0	Approved	[2]
Lovastatin	DM9OZWQ	Hypercholesterolaemia	5C80.0	Approved	[7]
Pitavastatin calcium	DM1UJO0	Dyslipidemia	5C80-5C81	Approved	[8], [9]
Pravastatin	DM6A0X7	Hypercholesterolaemia	5C80.0	Approved	[10]
Rosuvastatin	DMMIQ7G	Hypercholesterolaemia	5C80.0	Approved	[11]
Simvastatin	DM30SGU	Hypercholesterolaemia	5C80.0	Approved	[2]
Teriflunomide	DMQ2FKJ	Hyperlipidaemia	5C80	Approved	[1]
TOCOTRIENOL	DM1UE67	Hyperlipidaemia	5C80	Approved	[12], [13]
LAROPIPRANT	DM5FABJ	Coronary heart disease	BA80.Z	Phase 4	[14], [15]

4 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Premarin/Pravachol	DMLSOB7	Hyperlipidaemia	5C80	Phase 3	[16]
CRILVASTATIN	DMO1ZGX	Hyperlipidaemia	5C80	Phase 2	[17], [13]
XZK-monascus	DMPI6N0	Hyperlipidaemia	5C80	Phase 2	[18]
NCX-6560	DMM7RC5	Cardiovascular disease	BA00-BE2Z	Phase 1	[16]

24 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
2-cyclopropyl-4-substituted-phenoxy-quinoline derivative 1	DMTJ1G8	N. A.	N. A.	Patented	[19]
Atorvastatin lactole derivative 1	DMRG1NL	N. A.	N. A.	Patented	[19]
Eptastatin derivative 1	DM7XYRA	N. A.	N. A.	Patented	[19]
Hexahydro naphthalene derivative 1	DMT2Z0I	N. A.	N. A.	Patented	[19]
Hexahydro naphthalene derivative 2	DMFG9HP	N. A.	N. A.	Patented	[19]
Hexahydro naphthalene derivative 3	DM1KT4I	N. A.	N. A.	Patented	[19]
Lactol derivative 1	DMWC3P5	N. A.	N. A.	Patented	[19]
Lactol derivative 2	DMP3GRA	N. A.	N. A.	Patented	[19]
Pitavastatin derivative 1	DMFZ9Q3	N. A.	N. A.	Patented	[19]
PMID27537201-Compound-Figure11	DM9C4XH	N. A.	N. A.	Patented	[19]
PMID27537201-Compound-Figure13b	DMPDTHQ	N. A.	N. A.	Patented	[19]
PMID27537201-Compound-Figure13c	DMWZ1PD	N. A.	N. A.	Patented	[19]
PMID27537201-Compound-Figure15a	DMVBJKH	N. A.	N. A.	Patented	[19]
PMID27537201-Compound-Figure15b	DMZ6N2J	N. A.	N. A.	Patented	[19]
PMID27537201-Compound-Figure17	DMWKVZD	N. A.	N. A.	Patented	[19]
Poly-substituted azoles statin lactone derivative 1	DMDLS54	N. A.	N. A.	Patented	[19]
Poly-substituted azoles statin lactone derivative 2	DM5G3CN	N. A.	N. A.	Patented	[19]
Poly-substituted miazine derivative 1	DMQJ38W	N. A.	N. A.	Patented	[19]
Quinoline derivative 1	DMRY2HL	N. A.	N. A.	Patented	[19]
Quinoline derivative 16	DMTHG87	N. A.	N. A.	Patented	[19]
Quinoline derivative 17	DMKULV8	N. A.	N. A.	Patented	[19]
Sterol derivative 1	DM5U36G	N. A.	N. A.	Patented	[19]
Sterol derivative 2	DME1B23	N. A.	N. A.	Patented	[19]
Sterol derivative 3	DMOT1FQ	N. A.	N. A.	Patented	[19]

12 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dalvastatin	DMZ38EN	Hyperlipidaemia	5C80	Discontinued in Phase 3	[20]
Bervastatin	DMEK6J0	Thrombosis	DB61-GB90	Discontinued in Phase 2	[21]
BMY-21950	DM2NBXR	Hyperlipidaemia	5C80	Discontinued in Phase 2	[22], [13]
GLENVASTATIN	DMT1LQS	Hyperlipidaemia	5C80	Discontinued in Phase 2	[23], [13]
RBx10558	DMYSADI	Hyperlipidaemia	5C80	Discontinued in Phase 2	[24]
PF-3052334	DMOQZIW	Arteriosclerosis	BD40	Discontinued in Phase 1	[25]
BMY-22089	DMZFTLK	Hyperlipidaemia	5C80	Terminated	[22], [13]
CP-83101	DMSOT07	Arteriosclerosis	BD40	Terminated	[26]
GT-16-239	DMA6RL2	Arteriosclerosis	BD40	Terminated	[27]
Mevastatin	DM1LGKP	N. A.	N. A.	Terminated	[28]
SQ-33600	DMT5LX0	Hyperlipidaemia	5C80	Terminated	[29]
SR12813	DMU2ZVY	Arteriosclerosis	BD40	Terminated	[30]

82 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(E)-5-octadecen-7,9-diynoic acid	DMIPY3W	Discovery agent	N.A.	Investigative	[31]
(E)-octadecan-9-ynoic acid	DMBLGF6	Discovery agent	N.A.	Investigative	[31]
(R)-Mevalonate	DMEXLUR	Discovery agent	N.A.	Investigative	[32]
(Z)-5-octadecen-7,9-diynoic acid	DM4X9GW	Discovery agent	N.A.	Investigative	[31]
(Z)-7-octedecan-9-ynoic acid	DMKWLSB	Discovery agent	N.A.	Investigative	[31]
1,4-Dithiothreitol	DMIFOXE	Discovery agent	N.A.	Investigative	[32]
2'-Monophosphoadenosine 5'-Diphosphoribose	DME9S8M	Discovery agent	N.A.	Investigative	[32]
3-(1,3 dodecadiynyl)-6-oxiranebutanoic acid	DMQC168	Discovery agent	N.A.	Investigative	[31]
3-Hydroxy-3-Methyl-Glutaric Acid	DMJD0UV	Discovery agent	N.A.	Investigative	[32], [33]
5-ketodihydromevinolin	DMXVPL1	Discovery agent	N.A.	Investigative	[34]
6-hydroxy-7,9-octadecadiynoic acid	DMPQTNK	Discovery agent	N.A.	Investigative	[31]
7,9-octadecadiynoic acid	DMO8GEI	Discovery agent	N.A.	Investigative	[31]
7,9-tetradecadiynoic acid	DMPEXTB	Discovery agent	N.A.	Investigative	[31]
9-octadecynoic acid	DM1DYU4	Discovery agent	N.A.	Investigative	[31]
BPL-001	DMKX6LY	Cardiovascular disease	BA00-BE2Z	Investigative	[35]
Brutieridin	DMKZM1L	Hypercholesterolaemia	5C80.0	Investigative	[35]
Coenzyme A	DM1I8LU	Discovery agent	N.A.	Investigative	[32]
DFGYVAE	DMR8M19	Discovery agent	N.A.	Investigative	[36]
F(4-Fluoro)VAE	DMTW571	Discovery agent	N.A.	Investigative	[37]
FPYVAE peptide	DMDUR4C	Discovery agent	N.A.	Investigative	[36]
GFPDGG	DMLM02I	Discovery agent	N.A.	Investigative	[37]
GFPEGG	DMGZTQW	Discovery agent	N.A.	Investigative	[37]
GFPTGG	DM9D8VH	Discovery agent	N.A.	Investigative	[37]
GLPDGG peptide	DMGTPDA	Discovery agent	N.A.	Investigative	[36]
GLPTGG	DME2YL6	Discovery agent	N.A.	Investigative	[37]
MT-001	DM7KIVX	Hypercholesterolaemia	5C80.0	Investigative	[35]
NCX-1067	DMUHXRA	Discovery agent	N.A.	Investigative	[35]
Nicotinamide-Adenine-Dinucleotide	DM9LRKB	N. A.	N. A.	Investigative	[32]
o-hydroxyatorvastatin	DMN37KO	Discovery agent	N.A.	Investigative	[38]
PMID1527791C29	DM7JKLM	Discovery agent	N.A.	Investigative	[39]
PMID15686906C17	DM50E6R	Discovery agent	N.A.	Investigative	[40]
PMID15686906C29	DMBZSKJ	Discovery agent	N.A.	Investigative	[40]
PMID1656041C11dd	DMJ8A4I	Discovery agent	N.A.	Investigative	[41]
PMID1656041C11ff	DM20TFH	Discovery agent	N.A.	Investigative	[41]
PMID1656041C11jj	DMLIXJW	Discovery agent	N.A.	Investigative	[41]
PMID1656041C11nn	DMNOMCT	Discovery agent	N.A.	Investigative	[41]
PMID1656041C4ff	DMW90GD	Discovery agent	N.A.	Investigative	[41]
PMID1656041C4rr	DMQGPJE	Discovery agent	N.A.	Investigative	[41]
PMID1656041C74	DMZVK16	Discovery agent	N.A.	Investigative	[41]
PMID17560788C29f	DMLX87P	Discovery agent	N.A.	Investigative	[42]
PMID17574411C41	DM6W73A	Discovery agent	N.A.	Investigative	[43]
PMID17574411C42	DM1YLF6	Discovery agent	N.A.	Investigative	[43]
PMID17574412C33	DM7HYPZ	Discovery agent	N.A.	Investigative	[44]
PMID18072721C50	DMK5PO8	Discovery agent	N.A.	Investigative	[25]
PMID18155906C16f	DM2U4NW	Discovery agent	N.A.	Investigative	[45]
PMID18412317C13b	DM6NL2B	Discovery agent	N.A.	Investigative	[46]
PMID1875346C18	DMTH0PD	Discovery agent	N.A.	Investigative	[47]
PMID1895299C1	DMA5P9Q	Discovery agent	N.A.	Investigative	[48]
PMID1895299C4p	DMAZWHB	Discovery agent	N.A.	Investigative	[48]
PMID1895299C6v	DM384PH	Discovery agent	N.A.	Investigative	[48]
PMID19502059C25d	DMTRL0X	Discovery agent	N.A.	Investigative	[49]
PMID1992138C8b	DMI3PCZ	Discovery agent	N.A.	Investigative	[50]
PMID1992149C13	DM2X1NY	Discovery agent	N.A.	Investigative	[51]
PMID1992149C9	DM9RENG	Discovery agent	N.A.	Investigative	[52]
PMID2153213C13b	DMUMYTB	Discovery agent	N.A.	Investigative	[53]
PMID2153213C13g	DM5TL2S	Discovery agent	N.A.	Investigative	[53]
PMID2153213C1a	DMVYB6Q	Discovery agent	N.A.	Investigative	[53]
PMID2153213C1e	DMRUJFZ	Discovery agent	N.A.	Investigative	[53]
PMID2153213C1f	DMOLIE1	Discovery agent	N.A.	Investigative	[53]
PMID2153213C2c	DMJ4126	Discovery agent	N.A.	Investigative	[53]
PMID2153213C2d	DMGAY4M	Discovery agent	N.A.	Investigative	[53]
PMID2153213C2f	DM6QXYE	Discovery agent	N.A.	Investigative	[53]
PMID2231594C3j	DMVI6EX	Discovery agent	N.A.	Investigative	[54]
PMID2231594C3k	DMJYHIM	Discovery agent	N.A.	Investigative	[54]
PMID2231594C3q	DMJQ5B0	Discovery agent	N.A.	Investigative	[54]
PMID2231594C3u	DMJ504Y	Discovery agent	N.A.	Investigative	[54]
PMID2296027C25	DMOKZ3R	Discovery agent	N.A.	Investigative	[55]
PMID2296027C29	DMY267E	Discovery agent	N.A.	Investigative	[55]
PMID2296036C2g	DM6VG8K	Discovery agent	N.A.	Investigative	[56]
PMID2296036C2t	DMBXCNA	Discovery agent	N.A.	Investigative	[56]
PMID2296036C4d	DMC6HQL	Discovery agent	N.A.	Investigative	[56]
PMID2296036C4i	DMSJ94N	Discovery agent	N.A.	Investigative	[56]
PMID2909732C7	DM9J5Q7	Discovery agent	N.A.	Investigative	[57]
PMID7932551C9	DM769YQ	Discovery agent	N.A.	Investigative	[58]
PMID8246233C28	DMRGY2X	Discovery agent	N.A.	Investigative	[59]
PMID8246233C35	DMUJ9F7	Discovery agent	N.A.	Investigative	[59]
PMID8246233C5ab	DMETHN7	Discovery agent	N.A.	Investigative	[59]
PMID8246234C3h	DMJWEXQ	Discovery agent	N.A.	Investigative	[60]
PMID8246237C18t	DMLOR6F	Discovery agent	N.A.	Investigative	[61]
PMID8426367C18	DMTURQZ	Discovery agent	N.A.	Investigative	[62]
rawsonol	DM9XOE6	Discovery agent	N.A.	Investigative	[63]
Statin	DM4WQHU	Hypercholesterolaemia	5C80.0	Investigative	[35]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Multiple myeloma	2C82	Bone marrow	1.48E-06	1.01	4.34
Familial hypercholesterolemia	5A11	Whole blood	1.01E-05	0.65	1.53
Coronary artery disease	BA80-BA8Z	Peripheral blood	1.85E-01	0.23	0.94

The Drug-Metabolizing Enzyme (DME) Role of This DTT

• DTT DME Name: HMG-CoA reductase (HMGCR) DME Info
• Gene Name: HMGCR

References

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