Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTIEMFN)

• DTT Name: TYRO3 tyrosine kinase receptor (TYRO3)
• Synonyms: Tyrosine-protein kinase receptor TYRO3; Tyrosine-protein kinase TIF; Tyrosine-protein kinase SKY; Tyrosine-protein kinase RSE; Tyrosine-protein kinase DTK; Tyrosine-protein kinase BYK; TIF; SKY; RSE; DTK; BYK
• Gene Name: TYRO3
• DTT Type: Clinical trial target; [1]
• UniProt ID: TYRO3_HUMAN
• TTD ID: T94880
• EC Number: EC 2.7.10.1
• Sequence:
  MALRRSMGRPGLPPLPLPPPPRLGLLLAALASLLLPESAAAGLKLMGAPVKLTVSQGQPV
  KLNCSVEGMEEPDIQWVKDGAVVQNLDQLYIPVSEQHWIGFLSLKSVERSDAGRYWCQVE
  DGGETEISQPVWLTVEGVPFFTVEPKDLAVPPNAPFQLSCEAVGPPEPVTIVWWRGTTKI
  GGPAPSPSVLNVTGVTQSTMFSCEAHNLKGLASSRTATVHLQALPAAPFNITVTKLSSSN
  ASVAWMPGADGRALLQSCTVQVTQAPGGWEVLAVVVPVPPFTCLLRDLVPATNYSLRVRC
  ANALGPSPYADWVPFQTKGLAPASAPQNLHAIRTDSGLILEWEEVIPEAPLEGPLGPYKL
  SWVQDNGTQDELTVEGTRANLTGWDPQKDLIVRVCVSNAVGCGPWSQPLVVSSHDRAGQQ
  GPPHSRTSWVPVVLGVLTALVTAAALALILLRKRRKETRFGQAFDSVMARGEPAVHFRAA
  RSFNRERPERIEATLDSLGISDELKEKLEDVLIPEQQFTLGRMLGKGEFGSVREAQLKQE
  DGSFVKVAVKMLKADIIASSDIEEFLREAACMKEFDHPHVAKLVGVSLRSRAKGRLPIPM
  VILPFMKHGDLHAFLLASRIGENPFNLPLQTLIRFMVDIACGMEYLSSRNFIHRDLAARN
  CMLAEDMTVCVADFGLSRKIYSGDYYRQGCASKLPVKWLALESLADNLYTVQSDVWAFGV
  TMWEIMTRGQTPYAGIENAEIYNYLIGGNRLKQPPECMEDVYDLMYQCWSADPKQRPSFT
  CLRMELENILGQLSVLSASQDPLYINIERAEEPTAGGSLELPGRDQPYSGAGDGSGMGAV
  GGTPSDCRYILTPGGLAEQPGQAEHQPESPLNETQRLLLLQQGLLPHSSC
• Function: Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to several ligands including TULP1 or GAS6. Regulates many physiological processes including cell survival, migration and differentiation. Ligand binding at the cell surface induces dimerization and autophosphorylation of TYRO3 on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with PIK3R1 and thereby enhances PI3-kinase activity. Activates the AKT survival pathway, including nuclear translocation of NF-kappa-B and up-regulation of transcription of NF-kappa-B-regulated genes. TYRO3 signaling plays a role in various processes such as neuron protection from excitotoxic injury, platelet aggregation and cytoskeleton reorganization. Plays also an important role in inhibition of Toll-like receptors (TLRs)-mediated innate immune response by activating STAT1, which selectively induces production of suppressors of cytokine signaling SOCS1 and SOCS3.

Molecular Interaction Atlas (MIA) of This DTT

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
RXDX-106	DM6NVTR	Solid tumour/cancer	2A00-2F9Z	Phase 1	[2]

7 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BDBM50444058	DM9GLQB	N. A.	N. A.	Patented	[3]
BDBM50444059	DMS0EMU	N. A.	N. A.	Patented	[3]
BDBM50444062	DMR2UGC	N. A.	N. A.	Patented	[3]
KRDULPYOVRWKMA-UHFFFAOYSA-N	DMRY7KV	N. A.	N. A.	Patented	[4]
US10053465, 12	DMPM8VB	N. A.	N. A.	Patented	[5]
US10053465, 5	DMV7BF2	N. A.	N. A.	Patented	[5]
US10053465, 8	DM42XWO	N. A.	N. A.	Patented	[4]

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
LDC1267	DMH7R6L	Discovery agent	N.A.	Investigative	[1]

References

• [1] The E3 ligase Cbl-b and TAM receptors regulate cancer metastasis via natural killer cells. Nature. 2014 Mar 27;507(7493):508-12.
• [2] National Cancer Institute Drug Dictionary (drug name RXDX106).
• [3] Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity. US9649309.
• [4] Pyrrolopyrimidine derivatives as TAM inhibitors. US10053465.
• [5] Fused bicyclic 1,2,4-triazine compounds as TAM inhibitors. US9708333.