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]
• 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

12 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Aspirin	DM672AH	Acute coronary syndrome	BA41	Approved	[1]
Atorvastatin	DMF28YC	Acute coronary syndrome	BA41	Approved	[2]
Cerivastatin	DMXCM7H	Hyperlipidaemia	5C80	Approved	[3]
Fluvastatin	DM4MDJY	Arteriosclerosis	BD40	Approved	[2]
Lovastatin	DM9OZWQ	Arteriosclerosis	BD40	Approved	[4]
PITAVASTATIN CALCIUM	DM1UJO0	Dyslipidemia	5C80-5C81	Approved	[5]
Pravastatin	DM6A0X7	Adult acute monocytic leukemia		Approved	[6]
Rosuvastatin	DMMIQ7G	Arteriosclerosis	BD40	Approved	[7]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[2]
Teriflunomide	DMQ2FKJ	Hyperlipidaemia	5C80	Approved	[1]
TOCOTRIENOL	DM1UE67	Hyperlipidaemia	5C80	Approved	[8]
LAROPIPRANT	DM5FABJ	Coronary heart disease	BA80.Z	Phase 4	[9]

3 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CRILVASTATIN	DMO1ZGX	Hyperlipidaemia	5C80	Phase 2	[10]
XZK-monascus	DMPI6N0	Hyperlipidaemia	5C80	Phase 2	[11]
NCX-6560	DMM7RC5	Cardiovascular disease	BA00-BE2Z	Phase 1	[12]

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	[13]
Atorvastatin lactole derivative 1	DMRG1NL	N. A.	N. A.	Patented	[13]
Hexahydro naphthalene derivative 1	DMT2Z0I	N. A.	N. A.	Patented	[13]
Hexahydro naphthalene derivative 2	DMFG9HP	N. A.	N. A.	Patented	[13]
Hexahydro naphthalene derivative 3	DM1KT4I	N. A.	N. A.	Patented	[13]
Lactol derivative 1	DMWC3P5	N. A.	N. A.	Patented	[13]
Lactol derivative 2	DMP3GRA	N. A.	N. A.	Patented	[13]
Pitavastatin derivative 1	DMFZ9Q3	N. A.	N. A.	Patented	[13]
PMID27537201-Compound-Figure11	DM9C4XH	N. A.	N. A.	Patented	[13]
PMID27537201-Compound-Figure13b	DMPDTHQ	N. A.	N. A.	Patented	[13]
PMID27537201-Compound-Figure13c	DMWZ1PD	N. A.	N. A.	Patented	[13]
PMID27537201-Compound-Figure15a	DMVBJKH	N. A.	N. A.	Patented	[13]
PMID27537201-Compound-Figure15b	DMZ6N2J	N. A.	N. A.	Patented	[13]
PMID27537201-Compound-Figure17	DMWKVZD	N. A.	N. A.	Patented	[13]
Poly-substituted azoles statin lactone derivative 1	DMDLS54	N. A.	N. A.	Patented	[13]
Poly-substituted azoles statin lactone derivative 2	DM5G3CN	N. A.	N. A.	Patented	[13]
Poly-substituted miazine derivative 1	DMQJ38W	N. A.	N. A.	Patented	[13]
Pravastatin derivative 1	DM7XYRA	N. A.	N. A.	Patented	[13]
Quinoline derivative 1	DMRY2HL	N. A.	N. A.	Patented	[13]
Quinoline derivative 16	DMTHG87	N. A.	N. A.	Patented	[13]
Quinoline derivative 17	DMKULV8	N. A.	N. A.	Patented	[13]
Sterol derivative 1	DM5U36G	N. A.	N. A.	Patented	[13]
Sterol derivative 2	DME1B23	N. A.	N. A.	Patented	[13]
Sterol derivative 3	DMOT1FQ	N. A.	N. A.	Patented	[13]

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	[14]
Bervastatin	DMEK6J0	Thrombosis	DB61-GB90	Discontinued in Phase 2	[15]
BMY-21950	DM2NBXR	Hyperlipidaemia	5C80	Discontinued in Phase 2	[16]
GLENVASTATIN	DMT1LQS	Hyperlipidaemia	5C80	Discontinued in Phase 2	[17]
RBx10558	DMYSADI	Hyperlipidaemia	5C80	Discontinued in Phase 2	[18]
PF-3052334	DMOQZIW	Arteriosclerosis	BD40	Discontinued in Phase 1	[19]
BMY-22089	DMZFTLK	Hyperlipidaemia	5C80	Terminated	[16]
CP-83101	DMSOT07	Arteriosclerosis	BD40	Terminated	[20]
GT-16-239	DMA6RL2	Arteriosclerosis	BD40	Terminated	[21]
Mevastatin	DM1LGKP	N. A.	N. A.	Terminated	[22]
SQ-33600	DMT5LX0	Hyperlipidaemia	5C80	Terminated	[23]
SR12813	DMU2ZVY	Arteriosclerosis	BD40	Terminated	[24]

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	[25]
(E)-octadecan-9-ynoic acid	DMBLGF6	Discovery agent	N.A.	Investigative	[25]
(R)-Mevalonate	DMEXLUR	Discovery agent	N.A.	Investigative	[26]
(Z)-5-octadecen-7,9-diynoic acid	DM4X9GW	Discovery agent	N.A.	Investigative	[25]
(Z)-7-octedecan-9-ynoic acid	DMKWLSB	Discovery agent	N.A.	Investigative	[25]
1,4-Dithiothreitol	DMIFOXE	Discovery agent	N.A.	Investigative	[26]
2'-Monophosphoadenosine 5'-Diphosphoribose	DME9S8M	Discovery agent	N.A.	Investigative	[26]
3-(1,3 dodecadiynyl)-6-oxiranebutanoic acid	DMQC168	Discovery agent	N.A.	Investigative	[25]
3-Hydroxy-3-Methyl-Glutaric Acid	DMJD0UV	Discovery agent	N.A.	Investigative	[26]
5-ketodihydromevinolin	DMXVPL1	Discovery agent	N.A.	Investigative	[27]
6-hydroxy-7,9-octadecadiynoic acid	DMPQTNK	Discovery agent	N.A.	Investigative	[25]
7,9-octadecadiynoic acid	DMO8GEI	Discovery agent	N.A.	Investigative	[25]
7,9-tetradecadiynoic acid	DMPEXTB	Discovery agent	N.A.	Investigative	[25]
9-octadecynoic acid	DM1DYU4	Discovery agent	N.A.	Investigative	[25]
BPL-001	DMKX6LY	Cardiovascular disease	BA00-BE2Z	Investigative	[28]
Brutieridin	DMKZM1L	Hypercholesterolaemia	5C80.0	Investigative	[28]
Coenzyme A	DM1I8LU	Discovery agent	N.A.	Investigative	[26]
DFGYVAE	DMR8M19	Discovery agent	N.A.	Investigative	[29]
F(4-Fluoro)VAE	DMTW571	Discovery agent	N.A.	Investigative	[30]
FPYVAE peptide	DMDUR4C	Discovery agent	N.A.	Investigative	[29]
GFPDGG	DMLM02I	Discovery agent	N.A.	Investigative	[30]
GFPEGG	DMGZTQW	Discovery agent	N.A.	Investigative	[30]
GFPTGG	DM9D8VH	Discovery agent	N.A.	Investigative	[30]
GLPDGG peptide	DMGTPDA	Discovery agent	N.A.	Investigative	[29]
GLPTGG	DME2YL6	Discovery agent	N.A.	Investigative	[30]
MT-001	DM7KIVX	Hypercholesterolaemia	5C80.0	Investigative	[28]
NCX-1067	DMUHXRA	Discovery agent	N.A.	Investigative	[28]
Nicotinamide-Adenine-Dinucleotide	DM9LRKB	N. A.	N. A.	Investigative	[26]
o-hydroxyatorvastatin	DMN37KO	Discovery agent	N.A.	Investigative	[31]
PMID1527791C29	DM7JKLM	Discovery agent	N.A.	Investigative	[32]
PMID15686906C17	DM50E6R	Discovery agent	N.A.	Investigative	[33]
PMID15686906C29	DMBZSKJ	Discovery agent	N.A.	Investigative	[33]
PMID1656041C11dd	DMJ8A4I	Discovery agent	N.A.	Investigative	[34]
PMID1656041C11ff	DM20TFH	Discovery agent	N.A.	Investigative	[34]
PMID1656041C11jj	DMLIXJW	Discovery agent	N.A.	Investigative	[34]
PMID1656041C11nn	DMNOMCT	Discovery agent	N.A.	Investigative	[34]
PMID1656041C4ff	DMW90GD	Discovery agent	N.A.	Investigative	[34]
PMID1656041C4rr	DMQGPJE	Discovery agent	N.A.	Investigative	[34]
PMID1656041C74	DMZVK16	Discovery agent	N.A.	Investigative	[34]
PMID17560788C29f	DMLX87P	Discovery agent	N.A.	Investigative	[35]
PMID17574411C41	DM6W73A	Discovery agent	N.A.	Investigative	[36]
PMID17574411C42	DM1YLF6	Discovery agent	N.A.	Investigative	[36]
PMID17574412C33	DM7HYPZ	Discovery agent	N.A.	Investigative	[37]
PMID18072721C50	DMK5PO8	Discovery agent	N.A.	Investigative	[19]
PMID18155906C16f	DM2U4NW	Discovery agent	N.A.	Investigative	[38]
PMID18412317C13b	DM6NL2B	Discovery agent	N.A.	Investigative	[39]
PMID1875346C18	DMTH0PD	Discovery agent	N.A.	Investigative	[40]
PMID1895299C1	DMA5P9Q	Discovery agent	N.A.	Investigative	[41]
PMID1895299C4p	DMAZWHB	Discovery agent	N.A.	Investigative	[41]
PMID1895299C6v	DM384PH	Discovery agent	N.A.	Investigative	[41]
PMID19502059C25d	DMTRL0X	Discovery agent	N.A.	Investigative	[42]
PMID1992138C8b	DMI3PCZ	Discovery agent	N.A.	Investigative	[43]
PMID1992149C13	DM2X1NY	Discovery agent	N.A.	Investigative	[44]
PMID1992149C9	DM9RENG	Discovery agent	N.A.	Investigative	[45]
PMID2153213C13b	DMUMYTB	Discovery agent	N.A.	Investigative	[46]
PMID2153213C13g	DM5TL2S	Discovery agent	N.A.	Investigative	[46]
PMID2153213C1a	DMVYB6Q	Discovery agent	N.A.	Investigative	[46]
PMID2153213C1e	DMRUJFZ	Discovery agent	N.A.	Investigative	[46]
PMID2153213C1f	DMOLIE1	Discovery agent	N.A.	Investigative	[46]
PMID2153213C2c	DMJ4126	Discovery agent	N.A.	Investigative	[46]
PMID2153213C2d	DMGAY4M	Discovery agent	N.A.	Investigative	[46]
PMID2153213C2f	DM6QXYE	Discovery agent	N.A.	Investigative	[46]
PMID2231594C3j	DMVI6EX	Discovery agent	N.A.	Investigative	[47]
PMID2231594C3k	DMJYHIM	Discovery agent	N.A.	Investigative	[47]
PMID2231594C3q	DMJQ5B0	Discovery agent	N.A.	Investigative	[47]
PMID2231594C3u	DMJ504Y	Discovery agent	N.A.	Investigative	[47]
PMID2296027C25	DMOKZ3R	Discovery agent	N.A.	Investigative	[48]
PMID2296027C29	DMY267E	Discovery agent	N.A.	Investigative	[48]
PMID2296036C2g	DM6VG8K	Discovery agent	N.A.	Investigative	[49]
PMID2296036C2t	DMBXCNA	Discovery agent	N.A.	Investigative	[49]
PMID2296036C4d	DMC6HQL	Discovery agent	N.A.	Investigative	[49]
PMID2296036C4i	DMSJ94N	Discovery agent	N.A.	Investigative	[49]
PMID2909732C7	DM9J5Q7	Discovery agent	N.A.	Investigative	[50]
PMID7932551C9	DM769YQ	Discovery agent	N.A.	Investigative	[51]
PMID8246233C28	DMRGY2X	Discovery agent	N.A.	Investigative	[52]
PMID8246233C35	DMUJ9F7	Discovery agent	N.A.	Investigative	[52]
PMID8246233C5ab	DMETHN7	Discovery agent	N.A.	Investigative	[52]
PMID8246234C3h	DMJWEXQ	Discovery agent	N.A.	Investigative	[53]
PMID8246237C18t	DMLOR6F	Discovery agent	N.A.	Investigative	[54]
PMID8426367C18	DMTURQZ	Discovery agent	N.A.	Investigative	[55]
rawsonol	DM9XOE6	Discovery agent	N.A.	Investigative	[56]
Statin	DM4WQHU	Hypercholesterolaemia	5C80.0	Investigative	[28]

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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