Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTONI0R)

• DTT Name: PKC-eta messenger RNA (PRKCH mRNA)
• Synonyms: nPKC-eta (mRNA); Protein kinase C eta type (mRNA); PRKCL (mRNA); PKCL (mRNA); PKC-L (mRNA)
• Gene Name: PRKCH
• DTT Type: Literature-reported target; [1]
• BioChemical Class: mRNA target
• UniProt ID: KPCL_HUMAN
• TTD ID: T40149
• EC Number: EC 2.7.11.13
• Sequence:
  MSSGTMKFNGYLRVRIGEAVGLQPTRWSLRHSLFKKGHQLLDPYLTVSVDQVRVGQTSTK
  QKTNKPTYNEEFCANVTDGGHLELAVFHETPLGYDHFVANCTLQFQELLRTTGASDTFEG
  WVDLEPEGKVFVVITLTGSFTEATLQRDRIFKHFTRKRQRAMRRRVHQINGHKFMATYLR
  QPTYCSHCREFIWGVFGKQGYQCQVCTCVVHKRCHHLIVTACTCQNNINKVDSKIAEQRF
  GINIPHKFSIHNYKVPTFCDHCGSLLWGIMRQGLQCKICKMNVHIRCQANVAPNCGVNAV
  ELAKTLAGMGLQPGNISPTSKLVSRSTLRRQGKESSKEGNGIGVNSSNRLGIDNFEFIRV
  LGKGSFGKVMLARVKETGDLYAVKVLKKDVILQDDDVECTMTEKRILSLARNHPFLTQLF
  CCFQTPDRLFFVMEFVNGGDLMFHIQKSRRFDEARARFYAAEIISALMFLHDKGIIYRDL
  KLDNVLLDHEGHCKLADFGMCKEGICNGVTTATFCGTPDYIAPEILQEMLYGPAVDWWAM
  GVLLYEMLCGHAPFEAENEDDLFEAILNDEVVYPTWLHEDATGILKSFMTKNPTMRLGSL
  TQGGEHAILRHPFFKEIDWAQLNHRQIEPPFRPRIKSREDVSNFDPDFIKEEPVLTPIDE
  GHLPMINQDEFRNFSYVSPELQP
• Function: In keratinocytes, binds and activates the tyrosine kinase FYN, which in turn blocks epidermal growth factor receptor (EGFR) signaling and leads to keratinocyte growth arrest and differentiation. Associates with the cyclin CCNE1-CDK2-CDKN1B complex and inhibits CDK2 kinase activity, leading to RB1 dephosphorylation and thereby G1 arrest in keratinocytes. In association with RALA activates actin depolymerization, which is necessary for keratinocyte differentiation. In the pre-B cell receptor signaling, functions downstream of BLNK by up-regulating IRF4, which in turn activates L chain gene rearrangement. Regulates epithelial tight junctions (TJs) by phosphorylating occludin (OCLN) on threonine residues, which is necessary for the assembly and maintenance of TJs. In association with PLD2 and via TLR4 signaling, is involved in lipopolysaccharide (LPS)-induced RGS2 down-regulation and foam cell formation. Upon PMA stimulation, mediates glioblastoma cell proliferation by activating the mTOR pathway, the PI3K/AKT pathway and the ERK1-dependent phosphorylation of ELK1. Involved in the protection of glioblastoma cells from irradiation-induced apoptosis by preventing caspase-9 activation. In camptothecin-treated MCF-7 cells, regulates NF-kappa-B upstream signaling by activating IKBKB, and confers protection against DNA damage-induced apoptosis. Promotes oncogenic functions of ATF2 in the nucleus while blocking its apoptotic function at mitochondria. Phosphorylates ATF2 which promotes its nuclear retention and transcriptional activity and negatively regulates its mitochondrial localization. Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that is involved in the regulation of cell differentiation in keratinocytes and pre-B cell receptor, mediates regulation of epithelial tight junction integrity and foam cell formation, and is required for glioblastoma proliferation and apoptosis prevention in MCF-7 cells.
• KEGG Pathway:
  Vascular smooth muscle contraction (hsa04270)
  Tight junction (hsa04530)
  Inflammatory mediator regulation of TRP channels (hsa04750)
• Reactome Pathway:
  G alpha (z) signalling events (R-HSA-418597)
  Effects of PIP2 hydrolysis (R-HSA-114508)

Molecular Interaction Atlas (MIA) of This DTT

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BALANOL	DMDLN9E	N. A.	N. A.	Terminated	[1]

13 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
8-Octyl-benzolactam-V9	DM4Z15M	Discovery agent	N.A.	Investigative	[2]
ISIS 6431	DMEUCI2	Discovery agent	N.A.	Investigative	[3]
ISIS 6432	DMQHN43	Discovery agent	N.A.	Investigative	[3]
ISIS 6434	DMNVLE2	Discovery agent	N.A.	Investigative	[3]
ISIS 6435	DMI7JQG	Discovery agent	N.A.	Investigative	[3]
ISIS 6442	DM7KSRG	Discovery agent	N.A.	Investigative	[3]
ISIS 6443	DMGN051	Discovery agent	N.A.	Investigative	[3]
ISIS 6445	DMXJ4SO	Discovery agent	N.A.	Investigative	[3]
ISIS 6553	DM5L387	Discovery agent	N.A.	Investigative	[3]
ISIS 6581	DMEAVPQ	Discovery agent	N.A.	Investigative	[3]
ISIS 6603	DMVXC7W	Discovery agent	N.A.	Investigative	[3]
LY-326449	DMN53M4	Discovery agent	N.A.	Investigative	[4]
PROSTRATIN	DM1HMJ5	Human immunodeficiency virus infection	1C62	Investigative	[5]

References

• [1] Evaluation of differential hypoxic cytotoxicity and electrochemical studies of nitro 5-deazaflavins, Bioorg. Med. Chem. Lett. 5(18):2155-2160 (1995).
• [2] Design and synthesis of 8-octyl-benzolactam-V9, a selective activator for protein kinase C epsilon and eta. J Med Chem. 2006 May 4;49(9):2681-8.
• [3] US patent application no. 5,959,096, Antisense oligonucleotides against human protein kinase C.
• [4] (S)-13-[(dimethylamino)methyl]-10,11,14,15-tetrahydro-4,9:16, 21-dimetheno-1H, 13H-dibenzo[e,k]pyrrolo[3,4-h][1,4,13]oxadiazacyclohexadecene-1,3(2H... J Med Chem. 1996 Jul 5;39(14):2664-71.
• [5] A nonpromoting phorbol from the samoan medicinal plant Homalanthus nutans inhibits cell killing by HIV-1. J Med Chem. 1992 May 29;35(11):1978-86.