Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKA2SUX)

• DOT Name: Tyrosine-protein kinase receptor UFO (AXL)
• Synonyms: EC 2.7.10.1; AXL oncogene
• Gene Name: AXL
• UniProt ID: UFO_HUMAN
• PDB ID: 2C5D; 4RA0; 5U6B; 5VXZ
• EC Number: 2.7.10.1
• Pfam ID: PF00041 ; PF13927 ; PF07714
• Sequence:
  MAWRCPRMGRVPLAWCLALCGWACMAPRGTQAEESPFVGNPGNITGARGLTGTLRCQLQV
  QGEPPEVHWLRDGQILELADSTQTQVPLGEDEQDDWIVVSQLRITSLQLSDTGQYQCLVF
  LGHQTFVSQPGYVGLEGLPYFLEEPEDRTVAANTPFNLSCQAQGPPEPVDLLWLQDAVPL
  ATAPGHGPQRSLHVPGLNKTSSFSCEAHNAKGVTTSRTATITVLPQQPRNLHLVSRQPTE
  LEVAWTPGLSGIYPLTHCTLQAVLSDDGMGIQAGEPDPPEEPLTSQASVPPHQLRLGSLH
  PHTPYHIRVACTSSQGPSSWTHWLPVETPEGVPLGPPENISATRNGSQAFVHWQEPRAPL
  QGTLLGYRLAYQGQDTPEVLMDIGLRQEVTLELQGDGSVSNLTVCVAAYTAAGDGPWSLP
  VPLEAWRPGQAQPVHQLVKEPSTPAFSWPWWYVLLGAVVAAACVLILALFLVHRRKKETR
  YGEVFEPTVERGELVVRYRVRKSYSRRTTEATLNSLGISEELKEKLRDVMVDRHKVALGK
  TLGEGEFGAVMEGQLNQDDSILKVAVKTMKIAICTRSELEDFLSEAVCMKEFDHPNVMRL
  IGVCFQGSERESFPAPVVILPFMKHGDLHSFLLYSRLGDQPVYLPTQMLVKFMADIASGM
  EYLSTKRFIHRDLAARNCMLNENMSVCVADFGLSKKIYNGDYYRQGRIAKMPVKWIAIES
  LADRVYTSKSDVWSFGVTMWEIATRGQTPYPGVENSEIYDYLRQGNRLKQPADCLDGLYA
  LMSRCWELNPQDRPSFTELREDLENTLKALPPAQEPDEILYVNMDEGGGYPEPPGAAGGA
  DPPTQPDPKDSCSCLTAAEVHPAGRYVLCPSTTPSPAQPADRGSPAAPGQEDGA
• Function: Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding growth factor GAS6 and which is thus regulating many physiological processes including cell survival, cell proliferation, migration and differentiation. Ligand binding at the cell surface induces dimerization and autophosphorylation of AXL. Following activation by ligand, AXL binds and induces tyrosine phosphorylation of PI3-kinase subunits PIK3R1, PIK3R2 and PIK3R3; but also GRB2, PLCG1, LCK and PTPN11. Other downstream substrate candidates for AXL are CBL, NCK2, SOCS1 and TNS2. Recruitment of GRB2 and phosphatidylinositol 3 kinase regulatory subunits by AXL leads to the downstream activation of the AKT kinase. GAS6/AXL signaling plays a role in various processes such as endothelial cell survival during acidification by preventing apoptosis, optimal cytokine signaling during human natural killer cell development, hepatic regeneration, gonadotropin-releasing hormone neuron survival and migration, platelet activation, or regulation of thrombotic responses. Also plays an important role in inhibition of Toll-like receptors (TLRs)-mediated innate immune response; (Microbial infection) Acts as a receptor for lassa virus and lymphocytic choriomeningitis virus, possibly through GAS6 binding to phosphatidyl-serine at the surface of virion envelope; (Microbial infection) Acts as a receptor for Ebolavirus, possibly through GAS6 binding to phosphatidyl-serine at the surface of virion envelope; (Microbial infection) Promotes Zika virus entry in glial cells, Sertoli cells and astrocytes. Additionally, Zika virus potentiates AXL kinase activity to antagonize type I interferon signaling and thereby promotes infection. Interferon signaling inhibition occurs via an SOCS1-dependent mechanism.
• Tissue Specificity: Highly expressed in metastatic colon tumors. Expressed in primary colon tumors. Weakly expressed in normal colon tissue.
• KEGG Pathway:
  EGFR tyrosine ki.se inhibitor resistance (hsa01521)
  Efferocytosis (hsa04148)
• Reactome Pathway: VEGFA-VEGFR2 Pathway (R-HSA-4420097)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 5 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Paclitaxel	DMLB81S	Approved	Tyrosine-protein kinase receptor UFO (AXL) increases the response to substance of Paclitaxel.	[24]
Vinblastine	DM5TVS3	Approved	Tyrosine-protein kinase receptor UFO (AXL) affects the response to substance of Vinblastine.	[25]
Capecitabine	DMTS85L	Approved	Tyrosine-protein kinase receptor UFO (AXL) decreases the response to substance of Capecitabine.	[24]
Warfarin	DMJYCVW	Approved	Tyrosine-protein kinase receptor UFO (AXL) increases the response to substance of Warfarin.	[23]
adenosine diphosphate	DMFUHKP	Investigative	Tyrosine-protein kinase receptor UFO (AXL) decreases the response to substance of adenosine diphosphate.	[26]

32 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 Tyrosine-protein kinase receptor UFO (AXL).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Tyrosine-protein kinase receptor UFO (AXL).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Tyrosine-protein kinase receptor UFO (AXL).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Tyrosine-protein kinase receptor UFO (AXL).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Tyrosine-protein kinase receptor UFO (AXL).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Tyrosine-protein kinase receptor UFO (AXL).	[6]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Tyrosine-protein kinase receptor UFO (AXL).	[7]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Tyrosine-protein kinase receptor UFO (AXL).	[8]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Tyrosine-protein kinase receptor UFO (AXL).	[9]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Tyrosine-protein kinase receptor UFO (AXL).	[10]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Tyrosine-protein kinase receptor UFO (AXL).	[11]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Tyrosine-protein kinase receptor UFO (AXL).	[12]
Etoposide	DMNH3PG	Approved	Etoposide increases the expression of Tyrosine-protein kinase receptor UFO (AXL).	[13]
Cidofovir	DMA13GD	Approved	Cidofovir increases the expression of Tyrosine-protein kinase receptor UFO (AXL).	[2]
Simvastatin	DM30SGU	Approved	Simvastatin decreases the expression of Tyrosine-protein kinase receptor UFO (AXL).	[14]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide increases the expression of Tyrosine-protein kinase receptor UFO (AXL).	[13]
Ifosfamide	DMCT3I8	Approved	Ifosfamide increases the expression of Tyrosine-protein kinase receptor UFO (AXL).	[2]
Clodronate	DM9Y6X7	Approved	Clodronate increases the expression of Tyrosine-protein kinase receptor UFO (AXL).	[2]
Adefovir dipivoxil	DMMAWY1	Approved	Adefovir dipivoxil increases the expression of Tyrosine-protein kinase receptor UFO (AXL).	[2]
Dactinomycin	DM2YGNW	Approved	Dactinomycin increases the expression of Tyrosine-protein kinase receptor UFO (AXL).	[13]
Plicamycin	DM7C8YV	Approved	Plicamycin decreases the expression of Tyrosine-protein kinase receptor UFO (AXL).	[15]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Tyrosine-protein kinase receptor UFO (AXL).	[16]
Napabucasin	DMDZ6Q3	Phase 3	Napabucasin decreases the expression of Tyrosine-protein kinase receptor UFO (AXL).	[17]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Tyrosine-protein kinase receptor UFO (AXL).	[11]
XL880	DMHJTR2	Phase 2	XL880 decreases the activity of Tyrosine-protein kinase receptor UFO (AXL).	[18]
MP470	DMELUAK	Phase 2	MP470 decreases the activity of Tyrosine-protein kinase receptor UFO (AXL).	[18]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Tyrosine-protein kinase receptor UFO (AXL).	[7]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Tyrosine-protein kinase receptor UFO (AXL).	[19]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Tyrosine-protein kinase receptor UFO (AXL).	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Tyrosine-protein kinase receptor UFO (AXL).	[21]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Tyrosine-protein kinase receptor UFO (AXL).	[22]
Vitamin K	DMN6EZY	Investigative	Vitamin K increases the expression of Tyrosine-protein kinase receptor UFO (AXL).	[23]

References

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