Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9W2SFH)

• DOT Name: Lanosterol synthase (LSS)
• Synonyms: EC 5.4.99.7; 2,3-epoxysqualene--lanosterol cyclase; Oxidosqualene--lanosterol cyclase; OSC; hOSC
• Gene Name: LSS
• Related Disease:
  Alopecia-intellectual disability syndrome 4
  Cataract 44
  Hypotrichosis 14
  Hypotrichosis simplex
• UniProt ID: LSS_HUMAN
• PDB ID: 1W6J; 1W6K
• EC Number: 5.4.99.7
• Pfam ID: PF13243 ; PF13249
• Sequence:
  MTEGTCLRRRGGPYKTEPATDLGRWRLNCERGRQTWTYLQDERAGREQTGLEAYALGLDT
  KNYFKDLPKAHTAFEGALNGMTFYVGLQAEDGHWTGDYGGPLFLLPGLLITCHVARIPLP
  AGYREEIVRYLRSVQLPDGGWGLHIEDKSTVFGTALNYVSLRILGVGPDDPDLVRARNIL
  HKKGGAVAIPSWGKFWLAVLNVYSWEGLNTLFPEMWLFPDWAPAHPSTLWCHCRQVYLPM
  SYCYAVRLSAAEDPLVQSLRQELYVEDFASIDWLAQRNNVAPDELYTPHSWLLRVVYALL
  NLYEHHHSAHLRQRAVQKLYEHIVADDRFTKSISIGPISKTINMLVRWYVDGPASTAFQE
  HVSRIPDYLWMGLDGMKMQGTNGSQIWDTAFAIQALLEAGGHHRPEFSSCLQKAHEFLRL
  SQVPDNPPDYQKYYRQMRKGGFSFSTLDCGWIVSDCTAEALKAVLLLQEKCPHVTEHIPR
  ERLCDAVAVLLNMRNPDGGFATYETKRGGHLLELLNPSEVFGDIMIDYTYVECTSAVMQA
  LKYFHKRFPEHRAAEIRETLTQGLEFCRRQQRADGSWEGSWGVCFTYGTWFGLEAFACMG
  QTYRDGTACAEVSRACDFLLSRQMADGGWGEDFESCEERRYLQSAQSQIHNTCWAMMGLM
  AVRHPDIEAQERGVRCLLEKQLPNGDWPQENIAGVFNKSCAISYTSYRNIFPIWALGRFS
  QLYPERALAGHP
• Function: Key enzyme in the cholesterol biosynthesis pathway. Catalyzes the cyclization of (S)-2,3 oxidosqualene to lanosterol, a reaction that forms the sterol nucleus. Through the production of lanosterol may regulate lens protein aggregation and increase transparency.
• Tissue Specificity: Widely expressed. Expressed in the hair bulb, the outer root sheath and hair matrix of the hair follicle epithelium. Also detected in dermal papilla, epidermis, sweat glands, sebaceous glands, and blood vessels.
• KEGG Pathway:
  Steroid biosynthesis (hsa00100)
  Metabolic pathways (hsa01100)
• Reactome Pathway:
  Activation of gene expression by SREBF (SREBP) (R-HSA-2426168)
  Cholesterol biosynthesis (R-HSA-191273)
• BioCyc Pathway: MetaCyc:HS08480-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alopecia-intellectual disability syndrome 4	DISESXS1	Strong	Autosomal recessive	[1]
Cataract 44	DISCHOB8	Strong	Autosomal recessive	[2]
Hypotrichosis 14	DISC82P6	Moderate	Autosomal recessive	[3]
Hypotrichosis simplex	DIS8WHDJ	Supportive	Autosomal dominant	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Lanosterol synthase (LSS) affects the response to substance of Fluorouracil.	[37]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Acocantherin	DM7JT24	Approved	Lanosterol synthase (LSS) increases the abundance of Acocantherin.	[38]

48 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 Lanosterol synthase (LSS).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Lanosterol synthase (LSS).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Lanosterol synthase (LSS).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Lanosterol synthase (LSS).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Lanosterol synthase (LSS).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Lanosterol synthase (LSS).	[9]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Lanosterol synthase (LSS).	[11]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Lanosterol synthase (LSS).	[12]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Lanosterol synthase (LSS).	[13]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Lanosterol synthase (LSS).	[14]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Lanosterol synthase (LSS).	[13]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Lanosterol synthase (LSS).	[15]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Lanosterol synthase (LSS).	[16]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Lanosterol synthase (LSS).	[17]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Lanosterol synthase (LSS).	[18]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Lanosterol synthase (LSS).	[19]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid decreases the expression of Lanosterol synthase (LSS).	[20]
Fluoxetine	DM3PD2C	Approved	Fluoxetine increases the expression of Lanosterol synthase (LSS).	[19]
Sertraline	DM0FB1J	Approved	Sertraline increases the expression of Lanosterol synthase (LSS).	[19]
Clavulanate	DM2FGRT	Approved	Clavulanate decreases the expression of Lanosterol synthase (LSS).	[21]
Thioridazine	DM35M8J	Approved	Thioridazine increases the expression of Lanosterol synthase (LSS).	[19]
Imipramine	DM2NUH3	Approved	Imipramine increases the expression of Lanosterol synthase (LSS).	[19]
Clomipramine	DMINRKW	Approved	Clomipramine increases the expression of Lanosterol synthase (LSS).	[19]
Erythromycin	DM4K7GQ	Approved	Erythromycin increases the expression of Lanosterol synthase (LSS).	[22]
Loratadine	DMF3AN7	Approved	Loratadine increases the expression of Lanosterol synthase (LSS).	[19]
Pentamidine	DMHZJCG	Approved	Pentamidine decreases the expression of Lanosterol synthase (LSS).	[19]
Flecainide	DMSQDLE	Approved	Flecainide increases the expression of Lanosterol synthase (LSS).	[22]
Perhexiline	DMINO7Z	Approved	Perhexiline increases the expression of Lanosterol synthase (LSS).	[19]
Clarithromycin	DM4M1SG	Approved	Clarithromycin decreases the expression of Lanosterol synthase (LSS).	[19]
Doxepin	DMPI98T	Approved	Doxepin increases the expression of Lanosterol synthase (LSS).	[23]
Isoflavone	DM7U58J	Phase 4	Isoflavone increases the expression of Lanosterol synthase (LSS).	[24]
Chlorpromazine	DMBGZI3	Phase 3 Trial	Chlorpromazine increases the expression of Lanosterol synthase (LSS).	[19]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Lanosterol synthase (LSS).	[19]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Lanosterol synthase (LSS).	[25]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene increases the expression of Lanosterol synthase (LSS).	[26]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Lanosterol synthase (LSS).	[4]
Chlorcyclizine	DM3L52Q	Phase 1	Chlorcyclizine increases the expression of Lanosterol synthase (LSS).	[19]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Lanosterol synthase (LSS).	[28]
ZIMELIDINE	DMNI3U2	Withdrawn from market	ZIMELIDINE increases the expression of Lanosterol synthase (LSS).	[22]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Lanosterol synthase (LSS).	[29]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Lanosterol synthase (LSS).	[30]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Lanosterol synthase (LSS).	[31]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Lanosterol synthase (LSS).	[21]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Lanosterol synthase (LSS).	[32]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride decreases the expression of Lanosterol synthase (LSS).	[33]
Arachidonic acid	DMUOQZD	Investigative	Arachidonic acid decreases the expression of Lanosterol synthase (LSS).	[34]
PP-242	DM2348V	Investigative	PP-242 decreases the expression of Lanosterol synthase (LSS).	[35]
Ganoderic acid A	DM42EVG	Investigative	Ganoderic acid A decreases the expression of Lanosterol synthase (LSS).	[36]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic decreases the ubiquitination of Lanosterol synthase (LSS).	[10]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Lanosterol synthase (LSS).	[27]

References

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