Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT0ZW9O)

• DTT Name: Ribosomal protein S6 kinase alpha-2 (RSK2)
• Synonyms: pp90RSK3; p90RSK2; p90-RSK 2; S6K-alpha-2; Ribosomal S6 kinase 3; RSK3; RSK-3; MAPKAPK1C; MAPKAPK-1c; MAPKAP kinase 1c; MAPK-activated protein kinase 1c; MAP kinase-activated protein kinase 1c; 90 kDa ribosomal protein S6 kinase 2
• Gene Name: RPS6KA2
• DTT Type: Literature-reported target; [1]
• Related Disease: Mature B-cell leukaemia [ICD-11: 2A82]
• BioChemical Class: Kinase
• UniProt ID: KS6A2_HUMAN
• TTD ID: T28043
• EC Number: EC 2.7.11.1
• Sequence:
  MDLSMKKFAVRRFFSVYLRRKSRSKSSSLSRLEEEGVVKEIDISHHVKEGFEKADPSQFE
  LLKVLGQGSYGKVFLVRKVKGSDAGQLYAMKVLKKATLKVRDRVRSKMERDILAEVNHPF
  IVKLHYAFQTEGKLYLILDFLRGGDLFTRLSKEVMFTEEDVKFYLAELALALDHLHSLGI
  IYRDLKPENILLDEEGHIKITDFGLSKEAIDHDKRAYSFCGTIEYMAPEVVNRRGHTQSA
  DWWSFGVLMFEMLTGSLPFQGKDRKETMALILKAKLGMPQFLSGEAQSLLRALFKRNPCN
  RLGAGIDGVEEIKRHPFFVTIDWNTLYRKEIKPPFKPAVGRPEDTFHFDPEFTARTPTDS
  PGVPPSANAHHLFRGFSFVASSLIQEPSQQDLHKVPVHPIVQQLHGNNIHFTDGYEIKED
  IGVGSYSVCKRCVHKATDTEYAVKIIDKSKRDPSEEIEILLRYGQHPNIITLKDVYDDGK
  FVYLVMELMRGGELLDRILRQRYFSEREASDVLCTITKTMDYLHSQGVVHRDLKPSNILY
  RDESGSPESIRVCDFGFAKQLRAGNGLLMTPCYTANFVAPEVLKRQGYDAACDIWSLGIL
  LYTMLAGFTPFANGPDDTPEEILARIGSGKYALSGGNWDSISDAAKDVVSKMLHVDPHQR
  LTAMQVLKHPWVVNREYLSPNQLSRQDVHLVKGAMAATYFALNRTPQAPRLEPVLSSNLA
  QRRGMKRLTSTRL
• Function: May function as tumor suppressor in epithelial ovarian cancer cells. Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of transcription factors, regulates translation, and mediates cellular proliferation, survival, and differentiation.
• KEGG Pathway:
  MAPK signaling pathway (hsa04010)
  Oocyte meiosis (hsa04114)
  mTOR signaling pathway (hsa04150)
  Thermogenesis (hsa04714)
  Long-term potentiation (hsa04720)
  Neurotrophin signaling pathway (hsa04722)
  Progesterone-mediated oocyte maturation (hsa04914)
  Insulin resistance (hsa04931)
  Yersinia infection (hsa05135)
  Chemical carcinogenesis - receptor activation (hsa05207)
• Reactome Pathway:
  CREB phosphorylation (R-HSA-199920)
  Senescence-Associated Secretory Phenotype (SASP) (R-HSA-2559582)
  Recycling pathway of L1 (R-HSA-437239)
  CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling (R-HSA-442742)
  RSK activation (R-HSA-444257)
  Gastrin-CREB signalling pathway via PKC and MAPK (R-HSA-881907)
  ERK/MAPK targets (R-HSA-198753)

Molecular Interaction Atlas (MIA) of This DTT

1 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BI-D1870	DMK3SAF	Chronic lymphocytic leukaemia	2A82.0	Preclinical	[1]

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PMID22564207C25b	DMBMYKQ	Discovery agent	N.A.	Investigative	[2]

References

• [1] BI-D1870 is a specific inhibitor of the p90 RSK (ribosomal S6 kinase) isoforms in vitro and in vivo. Biochem J. 2007 Jan 1;401(1):29-38.
• [2] Discovery of an orally efficacious inhibitor of anaplastic lymphoma kinase. J Med Chem. 2012 May 24;55(10):4580-93.