Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTV3NH6)

• DTT Name: Calmodulin (CALM)
• Synonyms: CaM; CALM2
• Gene Name: CALM
• DTT Type: Successful target; [1]
• Related Disease:
  Cardiac arrhythmia [ICD-11: BC9Z]
  Malaria [ICD-11: 1F40-1F45]
  Schizophrenia [ICD-11: 6A20]
• BioChemical Class: Calmodulin-dependent secretion
• UniProt ID: CALM1_HUMAN ; CALM2_HUMAN ; CALM3_HUMAN
• TTD ID: T39610
• Sequence:
  MADQLTEEQIAEFKEAFSLFDKDGDGTITTKELGTVMRSLGQNPTEAELQDMINEVDADG
  NGTIDFPEFLTMMARKMKDTDSEEEIREAFRVFDKDGNGYISAAELRHVMTNLGEKLTDE
  EVDEMIREADIDGDGQVNYEEFVQMMTAK
• Function: Calmodulin mediates the control of a largenumber of enzymes by ca(2+). Among the enzymes to be stimulated by the calmodulin-ca(2+) complex are a number of protein kinases and phosphatases.
• KEGG Pathway:
  Ras signaling pathway (hsa04014)
  Rap1 signaling pathway (hsa04015)
  Calcium signaling pathway (hsa04020)
  cGMP-PKG signaling pathway (hsa04022)
  cAMP signaling pathway (hsa04024)
  Phosphatidylinositol signaling system (hsa04070)
  Oocyte meiosis (hsa04114)
  Adrenergic signaling in cardiomyocytes (hsa04261)
  Vascular smooth muscle contraction (hsa04270)
  Circadian entrainment (hsa04713)
  Long-term potentiation (hsa04720)
  Neurotrophin signaling pathway (hsa04722)
  Dopaminergic synapse (hsa04728)
  Olfactory transduction (hsa04740)
  Phototransduction (hsa04744)
  Inflammatory mediator regulation of TRP channels (hsa04750)
  Insulin signaling pathway (hsa04910)
  GnRH signaling pathway (hsa04912)
  Estrogen signaling pathway (hsa04915)
  Melanogenesis (hsa04916)
  Oxytocin signaling pathway (hsa04921)
  Glucagon signaling pathway (hsa04922)
  Salivary secretion (hsa04970)
  Gastric acid secretion (hsa04971)
  Alzheimer's disease (hsa05010)
  Amphetamine addiction (hsa05031)
  Alcoholism (hsa05034)
  Pertussis (hsa05133)
  Tuberculosis (hsa05152)
  Glioma (hsa05214)
• Reactome Pathway:
  Platelet degranulation (R-HSA-114608)
  Translocation of GLUT4 to the plasma membrane (R-HSA-1445148)
  Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation (R-HSA-1474151)
  DARPP-32 events (R-HSA-180024)
  eNOS activation (R-HSA-203615)
  Inactivation, recovery and regulation of the phototransduction cascade (R-HSA-2514859)
  FCERI mediated Ca+2 mobilization (R-HSA-2871809)
  Ca2+ pathway (R-HSA-4086398)
  CREB phosphorylation through the activation of CaMKII (R-HSA-442729)
  Ras activation uopn Ca2+ infux through NMDA receptor (R-HSA-442982)
  Smooth Muscle Contraction (R-HSA-445355)
  VEGFR2 mediated vascular permeability (R-HSA-5218920)
  VEGFR2 mediated cell proliferation (R-HSA-5218921)
  RHO GTPases activate IQGAPs (R-HSA-5626467)
  RAF/MAP kinase cascade (R-HSA-5673001)
  Antigen activates B Cell Receptor (BCR) leading to generation of second messengers (R-HSA-983695)
  Calmodulin induced events (R-HSA-111933)

Molecular Interaction Atlas (MIA) of This DTT

3 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Aprindine	DMBXWU8	Cardiac arrhythmias	BC9Z	Approved	[2]
Halofantrine	DMOMK1V	Malaria	1F40-1F45	Approved	[3]
Trifluoperazine	DMKBYWI	Schizophrenia	6A20	Approved	[1]

7 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
2-Methyl-2,4-Pentanediol	DMD45CU	Discovery agent	N.A.	Investigative	[4]
2-Methyl-2-Propanol	DMHM5GJ	Discovery agent	N.A.	Investigative	[4]
Acetate Ion	DMD08RH	Discovery agent	N.A.	Investigative	[4]
Cacodylate Ion	DMK4XLD	Discovery agent	N.A.	Investigative	[4]
Calmidazolium	DM5ZTJL	Huntington disease	8A01.10	Investigative	[5]
MYRISTIC ACID	DMYX0BL	Discovery agent	N.A.	Investigative	[6]
N-Trimethyllysine	DMZQXLS	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
Schizophrenia	6A20	Pre-frontal cortex	6.44E-01	0.09	0.15
Schizophrenia	6A20	Superior temporal cortex	5.89E-01	-3.28E-04	-1.09E-03

References

• [1] Inhibitory effect of jujuboside A on glutamate-mediated excitatory signal pathway in hippocampus. Planta Med. 2003 Aug;69(8):692-5.
• [2] Aprindine inhibits calmodulin-stimulated phosphodiesterase and Ca-ATPase activities. J Cardiovasc Pharmacol. 1983 Jan-Feb;5(1):151-6.
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [4] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [5] Calmidazolium evokes high calcium fluctuations in Plasmodium falciparum. Cell Signal. 2016 Mar;28(3):125-135.
• [6] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.