Details of Drug Off-Target (DOT)

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

• DOT Name: Neuropilin-1 (NRP1)
• Synonyms: Vascular endothelial cell growth factor 165 receptor; CD antigen CD304
• Gene Name: NRP1
• Related Disease: Congenital heart disease
• UniProt ID: NRP1_HUMAN
• PDB ID: 1KEX; 2QQI; 2QQM; 2QQN; 3I97; 4DEQ; 4RN5; 5C7G; 5IJR; 5IYY; 5J1X; 5JGI; 5JGQ; 5JHK; 5L73; 6FMC; 6FMF; 6TKK; 7JJC; 7O1N; 7P5U; 8PFE
• Pfam ID: PF00431 ; PF11980 ; PF00754 ; PF00629
• Sequence:
  MERGLPLLCAVLALVLAPAGAFRNDKCGDTIKIESPGYLTSPGYPHSYHPSEKCEWLIQA
  PDPYQRIMINFNPHFDLEDRDCKYDYVEVFDGENENGHFRGKFCGKIAPPPVVSSGPFLF
  IKFVSDYETHGAGFSIRYEIFKRGPECSQNYTTPSGVIKSPGFPEKYPNSLECTYIVFVP
  KMSEIILEFESFDLEPDSNPPGGMFCRYDRLEIWDGFPDVGPHIGRYCGQKTPGRIRSSS
  GILSMVFYTDSAIAKEGFSANYSVLQSSVSEDFKCMEALGMESGEIHSDQITASSQYSTN
  WSAERSRLNYPENGWTPGEDSYREWIQVDLGLLRFVTAVGTQGAISKETKKKYYVKTYKI
  DVSSNGEDWITIKEGNKPVLFQGNTNPTDVVVAVFPKPLITRFVRIKPATWETGISMRFE
  VYGCKITDYPCSGMLGMVSGLISDSQITSSNQGDRNWMPENIRLVTSRSGWALPPAPHSY
  INEWLQIDLGEEKIVRGIIIQGGKHRENKVFMRKFKIGYSNNGSDWKMIMDDSKRKAKSF
  EGNNNYDTPELRTFPALSTRFIRIYPERATHGGLGLRMELLGCEVEAPTAGPTTPNGNLV
  DECDDDQANCHSGTGDDFQLTGGTTVLATEKPTVIDSTIQSEFPTYGFNCEFGWGSHKTF
  CHWEHDNHVQLKWSVLTSKTGPIQDHTGDGNFIYSQADENQKGKVARLVSPVVYSQNSAH
  CMTFWYHMSGSHVGTLRVKLRYQKPEEYDQLVWMAIGHQGDHWKEGRVLLHKSLKLYQVI
  FEGEIGKGNLGGIAVDDISINNHISQEDCAKPADLDKKNPEIKIDETGSTPGYEGEGEGD
  KNISRKPGNVLKTLDPILITIIAMSALGVLLGAVCGVVLYCACWHNGMSERNLSALENYN
  FELVDGVKLKKDKLNTQSTYSEA
• Function: Cell-surface receptor involved in the development of the cardiovascular system, in angiogenesis, in the formation of certain neuronal circuits and in organogenesis outside the nervous system. Mediates the chemorepulsant activity of semaphorins. Recognizes a C-end rule (CendR) motif R/KXXR/K on its ligands which causes cellular internalization and vascular leakage. It binds to semaphorin 3A, the PLGF-2 isoform of PGF, the VEGF165 isoform of VEGFA and VEGFB. Coexpression with KDR results in increased VEGF165 binding to KDR as well as increased chemotaxis. Regulates VEGF-induced angiogenesis. Binding to VEGFA initiates a signaling pathway needed for motor neuron axon guidance and cell body migration, including for the caudal migration of facial motor neurons from rhombomere 4 to rhombomere 6 during embryonic development. Regulates mitochondrial iron transport via interaction with ABCB8/MITOSUR ; (Microbial infection) Acts as a host factor for human coronavirus SARS-CoV-2 infection. Recognizes and binds to CendR motif RRAR on SARS-CoV-2 spike protein S1 which enhances SARS-CoV-2 infection; [Isoform 2]: Binds VEGF-165 and may inhibit its binding to cells. May induce apoptosis by sequestering VEGF-165. May bind as well various members of the semaphorin family. Its expression has an averse effect on blood vessel number and integrity.
• Tissue Specificity: .The expression of isoforms 1 and 2 does not seem to overlap. Expressed in olfactory epithelium (at protein level) . Expressed in fibroblasts (at protein level) . Expressed by the blood vessels of different tissues. In the developing embryo it is found predominantly in the nervous system. In adult tissues, it is highly expressed in heart and placenta; moderately in lung, liver, skeletal muscle, kidney and pancreas; and low in adult brain . Expressed in the central nervous system, including olfactory related regions such as the olfactory tubercles and paraolfactory gyri .; [Isoform 2]: The expression of isoforms 1 and 2 does not seem to overlap. Found in liver hepatocytes, kidney distal and proximal tubules.
• KEGG Pathway:
  Axon guidance (hsa04360)
  Human T-cell leukemia virus 1 infection (hsa05166)
  Coro.virus disease - COVID-19 (hsa05171)
• Reactome Pathway:
  Signaling by ROBO receptors (R-HSA-376176)
  Sema3A PAK dependent Axon repulsion (R-HSA-399954)
  SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion (R-HSA-399955)
  CRMPs in Sema3A signaling (R-HSA-399956)
  Signal transduction by L1 (R-HSA-445144)
  CHL1 interactions (R-HSA-447041)
  Attachment and Entry (R-HSA-9694614)
  Neurophilin interactions with VEGF and VEGFR (R-HSA-194306)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Congenital heart disease	DISQBA23	Limited	Autosomal recessive	[1]

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Neuropilin-1 (NRP1) decreases the response to substance of Fluorouracil.	[35]
Simvastatin	DM30SGU	Approved	Neuropilin-1 (NRP1) decreases the response to substance of Simvastatin.	[36]
Gemcitabine	DMSE3I7	Approved	Neuropilin-1 (NRP1) decreases the response to substance of Gemcitabine.	[35]

35 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Neuropilin-1 (NRP1).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Neuropilin-1 (NRP1).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Neuropilin-1 (NRP1).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Neuropilin-1 (NRP1).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Neuropilin-1 (NRP1).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Neuropilin-1 (NRP1).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Neuropilin-1 (NRP1).	[8]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Neuropilin-1 (NRP1).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Neuropilin-1 (NRP1).	[10]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Neuropilin-1 (NRP1).	[11]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Neuropilin-1 (NRP1).	[12]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Neuropilin-1 (NRP1).	[13]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Neuropilin-1 (NRP1).	[14]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Neuropilin-1 (NRP1).	[7]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Neuropilin-1 (NRP1).	[15]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Neuropilin-1 (NRP1).	[16]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Neuropilin-1 (NRP1).	[17]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of Neuropilin-1 (NRP1).	[18]
Paclitaxel	DMLB81S	Approved	Paclitaxel increases the expression of Neuropilin-1 (NRP1).	[19]
Menthol	DMG2KW7	Approved	Menthol increases the expression of Neuropilin-1 (NRP1).	[20]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol increases the expression of Neuropilin-1 (NRP1).	[21]
Melphalan	DMOLNHF	Approved	Melphalan decreases the expression of Neuropilin-1 (NRP1).	[22]
Bicalutamide	DMZMSPF	Approved	Bicalutamide decreases the expression of Neuropilin-1 (NRP1).	[23]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Neuropilin-1 (NRP1).	[24]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Neuropilin-1 (NRP1).	[14]
Genistein	DM0JETC	Phase 2/3	Genistein affects the expression of Neuropilin-1 (NRP1).	[25]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Neuropilin-1 (NRP1).	[14]
PD-0325901	DM27D4J	Phase 2	PD-0325901 decreases the expression of Neuropilin-1 (NRP1).	[26]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Neuropilin-1 (NRP1).	[27]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Neuropilin-1 (NRP1).	[28]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Neuropilin-1 (NRP1).	[29]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Neuropilin-1 (NRP1).	[30]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Neuropilin-1 (NRP1).	[32]
Manganese	DMKT129	Investigative	Manganese increases the expression of Neuropilin-1 (NRP1).	[33]
Nitrobenzanthrone	DMN6L70	Investigative	Nitrobenzanthrone increases the expression of Neuropilin-1 (NRP1).	[34]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Neuropilin-1 (NRP1).	[31]

References

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