Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTZQTY2)

• DTT Name: DMPK messenger RNA (DMPK mRNA)
• Synonyms: Myotonin-protein kinase (mRNA); Myotonic dystrophy protein kinase (mRNA); MT-PK (mRNA); MDPK (mRNA); DMPK (mRNA); DMK (mRNA); DM1PK (mRNA); DM1 protein kinase (mRNA); DM-kinase (mRNA)
• Gene Name: DMPK
• DTT Type: Clinical trial target; [1]
• BioChemical Class: mRNA target
• UniProt ID: DMPK_HUMAN
• TTD ID: T68766
• EC Number: EC 2.7.11.1
• Sequence:
  MSAEVRLRRLQQLVLDPGFLGLEPLLDLLLGVHQELGASELAQDKYVADFLQWAEPIVVR
  LKEVRLQRDDFEILKVIGRGAFSEVAVVKMKQTGQVYAMKIMNKWDMLKRGEVSCFREER
  DVLVNGDRRWITQLHFAFQDENYLYLVMEYYVGGDLLTLLSKFGERIPAEMARFYLAEIV
  MAIDSVHRLGYVHRDIKPDNILLDRCGHIRLADFGSCLKLRADGTVRSLVAVGTPDYLSP
  EILQAVGGGPGTGSYGPECDWWALGVFAYEMFYGQTPFYADSTAETYGKIVHYKEHLSLP
  LVDEGVPEEARDFIQRLLCPPETRLGRGGAGDFRTHPFFFGLDWDGLRDSVPPFTPDFEG
  ATDTCNFDLVEDGLTAMVSGGGETLSDIREGAPLGVHLPFVGYSYSCMALRDSEVPGPTP
  MELEAEQLLEPHVQAPSLEPSVSPQDETAEVAVPAAVPAAEAEAEVTLRELQEALEEEVL
  TRQSLSREMEAIRTDNQNFASQLREAEARNRDLEAHVRQLQERMELLQAEGATAVTGVPS
  PRATDPPSHLDGPPAVAVGQCPLVGPGPMHRRHLLLPARVPRPGLSEALSLLLFAVVLSR
  AAALGCIGLVAHAGQLTAVWRRPGAARAP
• Function: May play a role in myocyte differentiation and survival by regulating the integrity of the nuclear envelope and the expression of muscle-specific genes. May also phosphorylate PPP1R12A and inhibit the myosin phosphatase activity to regulate myosin phosphorylation. Also critical to the modulation of cardiac contractility and to the maintenance of proper cardiac conduction activity probably through the regulation of cellular calcium homeostasis. Phosphorylates PLN, a regulator of calcium pumps and may regulate sarcoplasmic reticulum calcium uptake in myocytes. May also phosphorylate FXYD1/PLM which is able to induce chloride currents. May also play a role in synaptic plasticity. Non-receptor serine/threonine protein kinase which is necessary for the maintenance of skeletal muscle structure and function.
• Reactome Pathway: Ion homeostasis (R-HSA-5578775)

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
ISIS-DMPK	DMH32LC	Myotonic dystrophy	8C71.0	Phase 1/2	[1]

3 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
2-MOE phosphorothioate gapmers	DM4IJXW	Myotonic dystrophy	8C71.0	Investigative	[2]
PRO-135	DMA2SBL	Myotonic dystrophy	8C71.0	Investigative	[2]
RKI-1447	DMGTAWC	Discovery agent	N.A.	Investigative	[3]

References

• [1] Clinical pipeline report, company report or official report of ISIS Pharmaceuticals.
• [2] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1505).
• [3] Pyridylthiazole-based ureas as inhibitors of Rho associated protein kinases (ROCK1 and 2). Medchemcomm. 2012 Jun 1;3(6):699-709.