Details of Drug-Metabolizing Enzyme (DME)

General Information of Drug-Metabolizing Enzyme (DME) (ID: DEIDTHQ)

• DME Name: Squalene synthase (FDFT1)
• Synonyms: Farnesyl-diphosphate farnesyltransferase; FPP:FPP farnesyltransferase; FDFT1; SQS; SS
• Gene Name: FDFT1
• UniProt ID: FDFT_HUMAN
• INTEDE ID: DME0571
• Gene ID: 2222
• EC Number:
  EC: 2.5.1.21
  Transferase
  Alkyl/aryl transferase
  Alkyl/aryl transferase
  EC: 2.5.1.21
• Lineage:
  Species: Homo sapiens
  Kingdom: Metazoa
  Phylum: Chordata
  Class: Mammalia
  Order: Primates
  Family: Hominidae
  Genus: Homo
  Species: Homo sapiens
• Sequence:
  MEFVKCLGHPEEFYNLVRFRIGGKRKVMPKMDQDSLSSSLKTCYKYLNQTSRSFAAVIQA
  LDGEMRNAVCIFYLVLRALDTLEDDMTISVEKKVPLLHNFHSFLYQPDWRFMESKEKDRQ
  VLEDFPTISLEFRNLAEKYQTVIADICRRMGIGMAEFLDKHVTSEQEWDKYCHYVAGLVG
  IGLSRLFSASEFEDPLVGEDTERANSMGLFLQKTNIIRDYLEDQQGGREFWPQEVWSRYV
  KKLGDFAKPENIDLAVQCLNELITNALHHIPDVITYLSRLRNQSVFNFCAIPQVMAIATL
  AACYNNQQVFKGAVKIRKGQAVTLMMDATNMPAVKAIIYQYMEEIYHRIPDSDPSSSKTR
  QIISTIRTQNLPNCQLISRSHYSPIYLSFVMLLAALSWQYLTTLSQVTEDYVQTGEH
• Function: This enzyme is the first specific enzyme in cholesterol biosynthesis, catalyzing the dimerization of two molecules of farnesyl diphosphate in a two-step reaction to form squalene.
• KEGG Pathway:
  Metabolic pathways (hsa01100)
  Steroid biosynthesis (hsa00100)
• Reactome Pathway:
  Cholesterol biosynthesis (R-HSA-191273)
  PPARA activates gene expression (R-HSA-1989781)
  Activation of gene expression by SREBF (SREBP) (R-HSA-2426168)

Molecular Interaction Atlas (MIA) of This DME

1 Discontinued Drug(s) Metabolized by This DME

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
SQ-32709	DMSQRXW	Arteriosclerosis	BD40	Discontinued in Phase 2	[28]

Molecular Expression Atlas (MEA) of This DME

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Acute myelocytic leukaemia	2B33.1	Bone marrow	7.32E-05	2.52E-01	6.50E-01
Alopecia	ED70	Skin from scalp	8.39E-01	8.60E-02	2.35E-01
Alzheimer's disease	8A20	Entorhinal cortex	7.59E-03	8.48E-02	2.82E-01
Ankylosing spondylitis	FA92.0	Pheripheral blood	2.04E-01	3.96E-01	1.15E+00
Aortic stenosis	BB70	Calcified aortic valve	8.70E-01	-1.12E-02	-1.17E-02
Apnea	7A40	Hyperplastic tonsil	8.93E-01	-3.55E-01	-5.39E-01
Arthropathy	FA00-FA5Z	Peripheral blood	3.42E-01	-5.82E-02	-2.91E-01
Asthma	CA23	Nasal and bronchial airway	2.84E-01	-1.39E-01	-2.38E-01
Atopic dermatitis	EA80	Skin	3.34E-02	-1.47E-01	-4.34E-01
Autism	6A02	Whole blood	4.48E-02	-2.29E-01	-5.82E-01
Autoimmune uveitis	9A96	Peripheral monocyte	6.56E-01	-1.48E-01	-2.85E-01
Autosomal dominant monocytopenia	4B04	Whole blood	7.97E-01	-3.16E-01	-5.00E-01
Bacterial infection of gingival	1C1H	Gingival tissue	3.32E-04	-1.81E-01	-5.05E-01
Batten disease	5C56.1	Whole blood	5.89E-01	-5.09E-02	-1.90E-01
Behcet's disease	4A62	Peripheral blood	3.00E-01	-9.32E-02	-3.22E-01
Bipolar disorder	6A60-6A6Z	Prefrontal cortex	1.70E-02	-1.72E-01	-6.10E-01
Bladder cancer	2C94	Bladder tissue	3.81E-05	-8.96E-01	-3.02E+00
Breast cancer	2C60-2C6Z	Breast tissue	1.51E-10	-2.05E-01	-3.15E-01
Cardioembolic stroke	8B11.20	Whole blood	4.90E-01	-4.23E-02	-1.82E-01
Cervical cancer	2C77	Cervical tissue	9.21E-02	3.18E-01	5.62E-01
Childhood onset rheumatic disease	FA20.Z	Peripheral blood	5.44E-01	-7.77E-03	-2.28E-02
Chronic hepatitis C	1E51.1	Whole blood	8.65E-01	-7.61E-02	-2.49E-01
Chronic obstructive pulmonary disease	CA22	Lung tissue	6.71E-01	-3.52E-02	-1.06E-01
Chronic obstructive pulmonary disease	CA22	Small airway epithelium	1.31E-02	-1.74E-01	-5.57E-01
Chronic rhinosinusitis	CA0A	Sinus mucosa tissue	1.85E-01	-6.38E-01	-7.99E-01
Colon cancer	2B90	Colon tissue	2.02E-08	-1.46E-01	-3.62E-01
Coronary artery disease	BA80-BA8Z	Peripheral blood	2.62E-01	1.21E+00	1.02E+00
Diffuse large B-cell lymphoma	2A81	Tonsil tissue	5.79E-01	-1.25E-01	-2.06E-01
Endometriosis	GA10	Endometrium tissue	7.08E-04	-4.72E-01	-8.14E-01
Familial hypercholesterolemia	5C80.00	Peripheral blood	4.16E-01	9.42E-02	7.28E-01
Familial hypercholesterolemia	5C80.00	Whole blood	7.85E-01	-9.18E-02	-3.76E-01
Gastric cancer	2B72	Gastric tissue	8.52E-01	-4.99E-01	-7.33E-01
Glioblastopma	2A00.00	Nervous tissue	3.46E-72	-7.76E-01	-1.50E+00
Glioma	2A00.0Y-2A00.0Z	Brain stem tissue	9.29E-01	1.76E-01	3.96E-01
Glioma	2A00.0Y-2A00.0Z	White matter tissue	7.38E-02	4.03E-01	5.13E-01
Head and neck cancer	2D42	Head and neck tissue	1.28E-23	-7.92E-01	-2.34E+00
HIV-associated neurocognitive impairment	8A2Y-8A2Z	White matter tissue	6.71E-01	1.45E-01	3.07E-01
Huntington's disease	8A01.10	Whole blood	7.47E-01	-2.20E-02	-4.61E-02
Idiopathic pulmonary fibrosis	CB03.4	Lung tissue	3.54E-03	-4.49E-01	-2.06E+00
Immunodeficiency	4A00-4A20	Peripheral blood	3.99E-01	9.58E-02	3.55E-01
Influenza	1E30	Whole blood	4.01E-02	-9.52E-01	-2.12E+00
Interstitial cystitis	GC00.3	Bladder tissue	2.19E-05	-9.67E-01	-1.76E+01
Intracranial aneurysm	8B01.0	Intracranial artery	1.38E-03	-5.99E-01	-1.67E+00
Irritable bowel syndrome	DD91.0	Rectal colon tissue	7.36E-02	-3.94E-02	-9.21E-02
Ischemic stroke	8B11	Peripheral blood	2.49E-01	-1.41E-01	-8.25E-01
Juvenile idiopathic arthritis	FA24	Peripheral blood	6.24E-04	-1.23E-01	-2.53E-01
Lateral sclerosis	8B60.4	Skin	7.45E-02	2.38E-01	9.96E-01
Lateral sclerosis	8B60.4	Cervical spinal cord	9.52E-01	-2.29E-01	-1.97E-01
Liver cancer	2C12.0	Liver tissue	7.79E-03	3.07E-01	4.80E-01
Liver failure	DB99.7-DB99.8	Liver tissue	7.90E-03	-7.08E-01	-7.43E-01
Lung cancer	2C25	Lung tissue	2.96E-18	-3.68E-01	-8.60E-01
Lupus erythematosus	4A40	Whole blood	6.01E-01	-4.78E-02	-1.22E-01
Major depressive disorder	6A70-6A7Z	Hippocampus	8.46E-01	-3.12E-02	-1.17E-01
Major depressive disorder	6A70-6A7Z	Whole blood	9.79E-01	-4.41E-02	-1.78E-01
Melanoma	2C30	Skin	4.08E-02	-2.51E-01	-3.57E-01
Multiple myeloma	2A83.1	Peripheral blood	9.54E-01	-2.33E-01	-2.52E-01
Multiple myeloma	2A83.1	Bone marrow	2.32E-05	8.36E-01	3.07E+00
Multiple sclerosis	8A40	Plasmacytoid dendritic cells	5.08E-01	-5.80E-02	-2.52E-01
Myelodysplastic syndrome	2A36-2A3Z	Bone marrow	1.02E-01	-8.43E-02	-1.87E-01
Myelofibrosis	2A20.2	Whole blood	1.14E-01	4.33E-01	1.75E+00
Myocardial infarction	BA41-BA50	Peripheral blood	1.14E-01	-1.51E-01	-2.91E-01
Myopathy	8C70.6	Muscle tissue	2.16E-02	-2.81E-01	-8.47E-01
Neonatal sepsis	KA60	Whole blood	9.69E-04	1.64E-01	5.14E-01
Neuroectodermal tumour	2A00.11	Brain stem tissue	1.13E-06	-1.21E+00	-3.04E+00
Non-alcoholic fatty liver disease	DB92	Liver tissue	4.26E-01	4.29E-01	4.74E-01
Obesity related type 2 diabetes	5A11	Omental adipose tissue	8.86E-02	2.59E-01	8.43E-01
Olive pollen allergy	CA08.00	Peripheral blood	9.58E-01	-5.70E-02	-8.58E-02
Oral cancer	2B6E	Oral tissue	6.08E-06	-6.10E-01	-1.28E+00
Osteoarthritis	FA00-FA0Z	Synovial tissue	9.78E-01	-3.55E-01	-2.74E-01
Osteoporosis	FB83.1	Bone marrow	9.57E-01	3.26E-02	1.09E-01
Ovarian cancer	2C73	Ovarian tissue	3.51E-01	2.64E-01	4.09E-01
Pancreatic cancer	2C10	Pancreas	1.30E-05	8.63E-01	1.68E+00
Parkinson's disease	8A00.0	Substantia nigra tissue	9.95E-01	3.13E-02	1.25E-01
Pediatric respiratory syncytial virus infection	CA40.11	Peripheral blood	1.93E-01	6.27E-02	4.34E-01
Pituitary cancer	2D12	Pituitary tissue	4.99E-03	7.72E-01	2.65E+00
Pituitary gonadotrope tumour	2D12	Pituitary tissue	1.34E-02	7.88E-01	2.93E+00
Polycystic ovary syndrome	5A80.1	Vastus lateralis muscle	2.07E-01	6.00E-02	2.34E-01
Polycythemia vera	2A20.4	Whole blood	1.34E-01	-6.19E-02	-2.64E-01
Pompe disease	5C51.3	Biceps muscle	2.54E-01	-2.77E-01	-1.12E+00
Preterm birth	KA21.4Z	Myometrium	3.10E-01	5.42E-01	8.04E-01
Prostate cancer	2C82	Prostate	3.80E-03	-1.90E-01	-2.53E-01
Psoriasis	EA90	Skin	6.07E-04	-7.98E-02	-2.34E-01
Rectal cancer	2B92	Rectal colon tissue	6.91E-01	5.48E-03	2.84E-02
Renal cancer	2C90-2C91	Kidney	2.75E-02	-4.30E-01	-7.63E-01
Retinoblastoma	2D02.2	Uvea	6.59E-01	1.92E-01	4.08E-01
Rheumatoid arthritis	FA20	Synovial tissue	2.96E-02	1.04E+00	1.10E+00
Rhinovirus infection	CA42.1	Nasal epithelium tissue	1.91E-01	-1.02E-01	-4.11E-01
Schizophrenia	6A20	Prefrontal cortex	2.66E-02	-3.71E-02	-1.12E-01
Schizophrenia	6A20	Superior temporal cortex	3.07E-01	-1.14E-01	-3.64E-01
Scleroderma	4A42.Z	Whole blood	3.73E-04	-3.23E-01	-2.03E+00
Seizure	8A60-8A6Z	Whole blood	8.97E-01	1.00E-01	4.07E-01
Sensitive skin	EK0Z	Skin	4.84E-01	-2.57E-02	-3.00E-01
Sepsis with septic shock	1G41	Whole blood	3.43E-01	-3.82E-02	-1.09E-01
Shwachman-Diamond syndrome	3A70.0	Bone marrow	8.48E-01	-8.94E-02	-3.79E-01
Sickle cell disease	3A51.0-3A51.3	Peripheral blood	6.50E-01	1.87E-01	2.94E-01
Simpson golabi behmel syndrome	LD2C	Adipose tissue	6.35E-01	-8.90E-02	-3.14E-01
Sjogren's syndrome	4A43.2	Salivary gland tissue	9.98E-02	-3.11E-01	-1.65E+00
Skin cancer	2C30-2C3Z	Skin	9.17E-09	-2.33E-01	-5.22E-01
Thrombocythemia	3B63	Whole blood	6.73E-02	-6.74E-02	-2.80E-01
Thrombocytopenia	3B64	Whole blood	2.91E-01	2.71E-01	3.97E-01
Thyroid cancer	2D10	Thyroid	1.08E-32	-5.82E-01	-2.26E+00
Tibial muscular dystrophy	8C75	Muscle tissue	5.94E-03	-3.64E-01	-1.08E+00
Tuberous sclerosis complex	LD2D.2	Perituberal tissue	3.05E-03	-7.08E-01	-3.15E+00
Type 2 diabetes	5A11	Liver tissue	7.75E-03	5.44E-01	2.48E+00
Ureter cancer	2C92	Urothelium	4.90E-01	-1.69E-01	-3.25E-01
Uterine cancer	2C78	Endometrium tissue	2.44E-01	1.26E-02	2.50E-02
Vitiligo	ED63.0	Skin	4.75E-01	1.30E-02	4.98E-02

The Drug Therapeutic Target (DTT) Role of This DME

• DME DTT Name: Squalene synthetase (FDFT1) DTT Info
• DME DTT Type: Discontinued

7 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Lapaquistat acetate	DMJY9CW	Hyperlipidaemia	5C80	Discontinued in Phase 3	[1]
BMS-187745	DMP8SIV	Hyperlipidaemia	5C80	Discontinued in Phase 2	[2]
SQ-32709	DMSQRXW	Arteriosclerosis	BD40	Discontinued in Phase 2	[3]
A-87049	DMUID46	N. A.	N. A.	Terminated	[4]
RPR-101821	DM21Y75	Arteriosclerosis	BD40	Terminated	[5]
SQ-34919	DMT7O9V	N. A.	N. A.	Terminated	[6]
Squalestatin 1	DM4JZPT	Arteriosclerosis	BD40	Terminated	[7]

67 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(Z)-3-[2-(9H-fluoren-2-yloxy)ethylidene]-quinuclidine hydrochloride 31	DMIQ14F	Discovery agent	N.A.	Investigative	[8]
1-allyl-2-[3-(isopropylamino)propoxy]-9H-carbazole	DMQJ9RZ	Discovery agent	N.A.	Investigative	[9]
1-allyl-2-[3-(isopropylamino)propoxy]-9H-xanthen-9-one	DMNDW4J	Discovery agent	N.A.	Investigative	[9]
2-[4-(2-Thienyl)phenyl]-4-methylmorpholin-2-ol	DM6R1XH	Discovery agent	N.A.	Investigative	[10]
3-[1'-{4'-(Benzyloxy)-phenyl}]-quinuclidine-2-ene	DMIHWAJ	Discovery agent	N.A.	Investigative	[11]
3-[7'-(Methoxy)-napht-2'-yl]-quinuclidine-2-ene	DM7IHUK	Discovery agent	N.A.	Investigative	[11]
BPH-652	DMX4WI7	Hypercholesterolaemia	5C80.0	Investigative	[12]
BPH-830	DM15L2J	Discovery agent	N.A.	Investigative	[13]
CP-294838	DM6BRLA	Discovery agent	N.A.	Investigative	[14]
E5700	DM8LPBF	Discovery agent	N.A.	Investigative	[15]
ER-119884	DMIQ801	Discovery agent	N.A.	Investigative	[15]
J-104118	DMQ8J3M	Discovery agent	N.A.	Investigative	[12]
J-104123	DMWF7RO	Discovery agent	N.A.	Investigative	[12]
L-731120	DM8WCUY	Discovery agent	N.A.	Investigative	[12]
L-731128	DMTHLUN	Discovery agent	N.A.	Investigative	[12]
L-735021	DM8BVJQ	Discovery agent	N.A.	Investigative	[16]
PMID12238936C3a	DMQZXMF	Discovery agent	N.A.	Investigative	[17]
PMID12238936C3f	DMO5J8N	Discovery agent	N.A.	Investigative	[17]
PMID17709461C4g	DMMB6NU	Discovery agent	N.A.	Investigative	[11]
PMID18754614C10	DM1JRGI	Discovery agent	N.A.	Investigative	[10]
PMID18754614C17	DMSVB9D	Discovery agent	N.A.	Investigative	[10]
PMID18754614C18	DMF7VZO	Discovery agent	N.A.	Investigative	[10]
PMID18754614C19	DMHSE96	Discovery agent	N.A.	Investigative	[10]
PMID18754614C4	DMQFYM4	Discovery agent	N.A.	Investigative	[10]
PMID18754614C7	DMVTLO0	Discovery agent	N.A.	Investigative	[10]
PMID18754614C8	DM7SCM3	Discovery agent	N.A.	Investigative	[10]
PMID18754614C9	DMPH7A6	Discovery agent	N.A.	Investigative	[10]
PMID19191557C14	DMG7D3I	Discovery agent	N.A.	Investigative	[2]
PMID19191557C19	DMXLVEC	Discovery agent	N.A.	Investigative	[2]
PMID19191557C21	DM5RIB0	Discovery agent	N.A.	Investigative	[2]
PMID19191557C3	DM1MEY3	Discovery agent	N.A.	Investigative	[2]
PMID19191557C32	DMH8QRI	Discovery agent	N.A.	Investigative	[2]
PMID19191557C35	DM09IEK	Discovery agent	N.A.	Investigative	[2]
PMID19191557C8	DMUWYA2	Discovery agent	N.A.	Investigative	[2]
PMID19456099C13	DMBU9E4	Discovery agent	N.A.	Investigative	[13]
PMID19456099C15	DMPZMS0	Discovery agent	N.A.	Investigative	[13]
PMID20299227C12	DMKAZ1O	Discovery agent	N.A.	Investigative	[18]
PMID20299227C20	DM9H6LZ	Discovery agent	N.A.	Investigative	[18]
PMID22464687C15a	DMCDOHA	Discovery agent	N.A.	Investigative	[19]
PMID7473541C11	DMB2MQW	Discovery agent	N.A.	Investigative	[20]
PMID7473541C19	DM2CP5J	Discovery agent	N.A.	Investigative	[20]
PMID7473541C20	DMMZ1LR	Discovery agent	N.A.	Investigative	[20]
PMID7473541C21	DMMRSZB	Discovery agent	N.A.	Investigative	[20]
PMID7629799C2d	DMOJ57D	Discovery agent	N.A.	Investigative	[21]
PMID7629799C2e	DMBRH0Q	Discovery agent	N.A.	Investigative	[21]
PMID7629799C6	DMXMF39	Discovery agent	N.A.	Investigative	[2]
PMID7650673C4q	DM5SU6N	Discovery agent	N.A.	Investigative	[22]
PMID7966163C3f	DMJF7OC	Discovery agent	N.A.	Investigative	[16]
PMID7966163C4e	DMD524S	Discovery agent	N.A.	Investigative	[16]
PMID7966163C6c	DMUEG8O	Discovery agent	N.A.	Investigative	[16]
PMID7966163C6d	DM0XU3C	Discovery agent	N.A.	Investigative	[16]
PMID7966163C6g	DM8T41N	Discovery agent	N.A.	Investigative	[16]
PMID8496919C7	DM8PBKQ	Discovery agent	N.A.	Investigative	[23]
PMID8576905C4	DMUJEA4	Discovery agent	N.A.	Investigative	[24]
PMID8709131C15	DMWBPOJ	Discovery agent	N.A.	Investigative	[25]
PMID8709131C17	DM10IQP	Discovery agent	N.A.	Investigative	[25]
PMID8709131C23	DMSKJ53	Discovery agent	N.A.	Investigative	[25]
PMID8709131C2a (+)	DM1OS6M	Discovery agent	N.A.	Investigative	[25]
PMID8709131C4	DMETC8A	Discovery agent	N.A.	Investigative	[25]
PMID9216829C5j	DM2F81A	Discovery agent	N.A.	Investigative	[4]
PMID9216829C5m	DM3ARWX	Discovery agent	N.A.	Investigative	[4]
PMID9871507C14	DMY28QM	Discovery agent	N.A.	Investigative	[26]
YM-75440	DMMCXWQ	Discovery agent	N.A.	Investigative	[9]
ZARAGOZIC ACID B	DMYRLA0	Discovery agent	N.A.	Investigative	[27]
Zaragozic Acid C	DMUQWP1	Discovery agent	N.A.	Investigative	[27]
Zaragozic Acid D	DMMTJE3	Discovery agent	N.A.	Investigative	[27]
Zaragozic Acid D2	DML4WQJ	Discovery agent	N.A.	Investigative	[27]

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