Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT3T17P)

• DTT Name: Phospholipase D1 (PLD1)
• Synonyms: Phosphatidylcholine-hydrolyzing phospholipase D1; PLD 1; HPLD1; Choline phosphatase 1
• Gene Name: PLD1
• DTT Type: Patented-recorded target; [1]
• BioChemical Class: Phosphoric diester hydrolase
• UniProt ID: PLD1_HUMAN
• TTD ID: T38996
• EC Number: EC 3.1.4.4
• Sequence:
  MSLKNEPRVNTSALQKIAADMSNIIENLDTRELHFEGEEVDYDVSPSDPKIQEVYIPFSA
  IYNTQGFKEPNIQTYLSGCPIKAQVLEVERFTSTTRVPSINLYTIELTHGEFKWQVKRKF
  KHFQEFHRELLKYKAFIRIPIPTRRHTFRRQNVREEPREMPSLPRSSENMIREEQFLGRR
  KQLEDYLTKILKMPMYRNYHATTEFLDISQLSFIHDLGPKGIEGMIMKRSGGHRIPGLNC
  CGQGRACYRWSKRWLIVKDSFLLYMKPDSGAIAFVLLVDKEFKIKVGKKETETKYGIRID
  NLSRTLILKCNSYRHARWWGGAIEEFIQKHGTNFLKDHRFGSYAAIQENALAKWYVNAKG
  YFEDVANAMEEANEEIFITDWWLSPEIFLKRPVVEGNRWRLDCILKRKAQQGVRIFIMLY
  KEVELALGINSEYTKRTLMRLHPNIKVMRHPDHVSSTVYLWAHHEKLVIIDQSVAFVGGI
  DLAYGRWDDNEHRLTDVGSVKRVTSGPSLGSLPPAAMESMESLRLKDKNEPVQNLPIQKS
  IDDVDSKLKGIGKPRKFSKFSLYKQLHRHHLHDADSISSIDSTSSYFNHYRSHHNLIHGL
  KPHFKLFHPSSESEQGLTRPHADTGSIRSLQTGVGELHGETRFWHGKDYCNFVFKDWVQL
  DKPFADFIDRYSTPRMPWHDIASAVHGKAARDVARHFIQRWNFTKIMKSKYRSLSYPFLL
  PKSQTTAHELRYQVPGSVHANVQLLRSAADWSAGIKYHEESIHAAYVHVIENSRHYIYIE
  NQFFISCADDKVVFNKIGDAIAQRILKAHRENQKYRVYVVIPLLPGFEGDISTGGGNALQ
  AIMHFNYRTMCRGENSILGQLKAELGNQWINYISFCGLRTHAELEGNLVTELIYVHSKLL
  IADDNTVIIGSANINDRSMLGKRDSEMAVIVQDTETVPSVMDGKEYQAGRFARGLRLQCF
  RVVLGYLDDPSEDIQDPVSDKFFKEVWVSTAARNATIYDKVFRCLPNDEVHNLIQLRDFI
  NKPVLAKEDPIRAEEELKKIRGFLVQFPFYFLSEESLLPSVGTKEAIVPMEVWT
• Function: May be involved in the regulation of perinuclear intravesicular membrane traffic. Implicated as a critical step in numerous cellular pathways, including signal transduction, membrane trafficking, and the regulation of mitosis.
• KEGG Pathway:
  Glycerophospholipid metabolism (hsa00564)
  Ether lipid metabolism (hsa00565)
  Metabolic pathways (hsa01100)
  Ras signaling pathway (hsa04014)
  cAMP signaling pathway (hsa04024)
  Sphingolipid signaling pathway (hsa04071)
  Endocytosis (hsa04144)
  Fc gamma R-mediated phagocytosis (hsa04666)
  Glutamatergic synapse (hsa04724)
  GnRH signaling pathway (hsa04912)
  Pathways in cancer (hsa05200)
  Pancreatic cancer (hsa05212)
  Choline metabolism in cancer (hsa05231)
• Reactome Pathway: Role of phospholipids in phagocytosis (R-HSA-2029485)
• BioCyc Pathway: MetaCyc:HS01185-MON

Molecular Interaction Atlas (MIA) of This DTT

6 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ML272	DMNEY58	N. A.	N. A.	Patented	[2]
US9127005, P0L	DMKLYCV	N. A.	N. A.	Patented	[3]
US9127005, P2B	DM3R7BT	N. A.	N. A.	Patented	[3]
US9127005, P2C	DMMT98V	N. A.	N. A.	Patented	[3]
US9453017, 1	DMVQ3IX	N. A.	N. A.	Patented	[2]
US9453017, 2	DMPH05Y	N. A.	N. A.	Patented	[2]

3 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
1-(pyridin-2-yl)piperazine	DMKE7FG	Discovery agent	N.A.	Investigative	[1]
1-(pyridin-4-yl)piperazine	DM78AJ1	Discovery agent	N.A.	Investigative	[1]
HALOPEMIDE	DMF6V8W	Discovery agent	N.A.	Investigative	[4]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Breast cancer	2C82	Breast tissue	7.36E-01	0.08	0.15

The Drug-Metabolizing Enzyme (DME) Role of This DTT

• DTT DME Name: Choline phosphatase 1 (PLD1) DME Info
• Gene Name: PLD1

1 Approved Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Miltefosine	DMND304	Chronic urticaria		Approved	[5]

References

• [1] Design and synthesis of isoform-selective phospholipase D (PLD) inhibitors. Part II. Identification of the 1,3,8-triazaspiro[4,5]decan-4-one privil... Bioorg Med Chem Lett. 2009 Apr 15;19(8):2240-3.
• [2] Antiviral therapies with phospholipase D inhibitors. US9453017.
• [3] Isoform selective phospholipase D inhibitors. US9127005.
• [4] Design of isoform-selective phospholipase D inhibitors that modulate cancer cell invasiveness. Nat Chem Biol. 2009 Feb;5(2):108-17.
• [5] Development of miltefosine as an oral treatment for leishmaniasis. Trans R Soc Trop Med Hyg. 2006 Dec;100 Suppl 1:S17-20.