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TM5614

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Identification

Generic Name
TM5614
DrugBank Accession Number
DB16516
Background

TM5614 is a novel, orally active, plasminogen activator inhibitor 1 (PAI-1) inhibitor1,2. PAI-1 is a marker of obesity, type 2 diabetes, and metabolic syndrome6,2,3, and current studies are exploring downstream effects of its inhibition. TM5614 inhibition of PAI-1, specifically, downregulates PCSK9 at the transcriptional level2. An animal study in mice fed a fast-food diet with TM5614 treatment showed improved metabolic measurements and reduced liver steatosis6,7. Further investigation of this compound is underway, including an exploratry Phase II study for its efficacy and safety for high-risk hospitalized patients with severe COVID-19 pneumonia8.

Type
Small Molecule
Groups
Investigational
Synonyms
Not Available
External IDs
  • TM5614
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Pharmacology

Indication

Not Available

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Pharmacodynamics

Not Available

Mechanism of action

TM5614 inhibits PAI-1 activity and is thought to consequently downregulate hepatic PCSK9 transcription, resulting in plasma decreases of PCSK92. Reduction of PCSK9 levels lowers catabolism of the LDL receptor, allowing more LDL-C to be cleared from the circulation2.

TargetActionsOrganism
UPlasminogen activator inhibitor 1Not AvailableHumans
Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Not Available

Half-life

Not Available

Clearance

Not Available

Adverse Effects
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Toxicity

Not Available

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Not Available
Food Interactions
Not Available

Categories

Drug Categories
Classification
Not classified
Affected organisms
Not Available

Chemical Identifiers

UNII
Not Available
CAS number
Not Available
InChI Key
Not Available
InChI
Not Available
IUPAC Name
Not Available
SMILES
Not Available

References

General References
  1. Yamaoka N, Murano K, Kodama H, Maeda A, Dan T, Nakabayashi T, Miyata T, Meguro K: Identification of novel plasminogen activator inhibitor-1 inhibitors with improved oral bioavailability: Structure optimization of N-acylanthranilic acid derivatives. Bioorg Med Chem Lett. 2018 Feb 15;28(4):809-813. doi: 10.1016/j.bmcl.2017.11.016. Epub 2018 Jan 6. [Article]
  2. Levine JA, Oleaga C, Eren M, Amaral AP, Shang M, Lux E, Khan SS, Shah SJ, Omura Y, Pamir N, Hay J, Barish G, Miyata T, Tavori H, Fazio S, Vaughan DE: Role of PAI-1 in hepatic steatosis and dyslipidemia. Sci Rep. 2021 Jan 11;11(1):430. doi: 10.1038/s41598-020-79948-x. [Article]
  3. Mertens I, Verrijken A, Michiels JJ, Van der Planken M, Ruige JB, Van Gaal LF: Among inflammation and coagulation markers, PAI-1 is a true component of the metabolic syndrome. Int J Obes (Lond). 2006 Aug;30(8):1308-14. doi: 10.1038/sj.ijo.0803189. Epub 2006 Jan 3. [Article]
  4. Hirai T, Asano K, Ito I, Miyazaki Y, Sugiura H, Agirbasli M, Kobayashi S, Kobayashi M, Shimada D, Natsume I, Kawasaki T, Ohba T, Tajiri S, Sakamaki F, Mineshita M, Takihara T, Sekiya K, Tomii K, Tomioka H, Kita H, Nishizaka Y, Fukui M, Miyata T, Harigae H: A randomized double-blind placebo-controlled trial of an inhibitor of plasminogen activator inhibitor-1 (TM5614) in mild to moderate COVID-19. Sci Rep. 2024 Jan 2;14(1):165. doi: 10.1038/s41598-023-50445-1. [Article]
  5. External Link [Link]
  6. Journal of the Endocrine Society [Link]
  7. Endocrine.org [Link]
  8. Cochrane Library Study [Link]
Not Available

Clinical Trials

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Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Not Available
Experimental Properties
Not Available
Predicted Properties
Not Available
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available
Chromatographic Properties
Collision Cross Sections (CCS)
Not Available

Targets

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Details1. Plasminogen activator inhibitor 1
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Serine protease inhibitor. Inhibits TMPRSS7 (PubMed:15853774). Is a primary inhibitor of tissue-type plasminogen activator (PLAT) and urokinase-type plasminogen activator (PLAU). As PLAT inhibitor, it is required for fibrinolysis down-regulation and is responsible for the controlled degradation of blood clots (PubMed:17912461, PubMed:8481516, PubMed:9207454). As PLAU inhibitor, it is involved in the regulation of cell adhesion and spreading (PubMed:9175705). Acts as a regulator of cell migration, independently of its role as protease inhibitor (PubMed:15001579, PubMed:9168821). It is required for stimulation of keratinocyte migration during cutaneous injury repair (PubMed:18386027). It is involved in cellular and replicative senescence (PubMed:16862142). Plays a role in alveolar type 2 cells senescence in the lung (By similarity). Is involved in the regulation of cementogenic differentiation of periodontal ligament stem cells, and regulates odontoblast differentiation and dentin formation during odontogenesis (PubMed:25808697, PubMed:27046084)
Specific Function
Protease binding
Gene Name
SERPINE1
Uniprot ID
P05121
Uniprot Name
Plasminogen activator inhibitor 1
Molecular Weight
45059.695 Da

Drug created at January 21, 2021 02:02 / Updated at July 12, 2024 11:44