Identification

Name
NN344
Accession Number
DB05115
Type
Small Molecule
Groups
Investigational
Description

NN344 is a neutral, soluble long-acting human insulin analogue with 24 hour coverage by once daily injection. NN344 has a very flat and predictable action profile. The product is intended for basal insulin treatment of diabetes mellitus.

Synonyms
Not Available
Categories
UNII
Not Available
CAS number
Not Available
Weight
Not Available
Chemical Formula
Not Available
InChI Key
Not Available
InChI
Not Available
IUPAC Name
Not Available
SMILES
Not Available

Pharmacology

Indication

Investigated for use/treatment in diabetes mellitus type 1 and 2.

Pharmacodynamics
Not Available
Mechanism of action

NN344 binds to the insulin receptor (IR), a heterotetrameric protein consisting of two extracellular alpha units and two transmembrane beta units. The binding of NN344 to the alpha subunit of IR stimulates the tyrosine kinase activity intrinsic to the beta subunit of the receptor. The bound receptor is able to autophosphorylate and phosphorylate numerous intracellular substrates such as insulin receptor substrates (IRS) proteins, Cbl, APS, Shc and Gab 1. These activated proteins, in turn, lead to the activation of downstream signaling molecules including PI3 kinase and Akt. Akt regulates the activity of glucose transporter 4 (GLUT4) and protein kinase C (PKC) which play a critical role in metabolism and catabolism.

TargetActionsOrganism
UInsulin receptorNot 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
Toxicity
Not Available
Affected organisms
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.
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be increased when combined with NN344.
2,4-thiazolidinedioneThe risk or severity of hypoglycemia can be increased when NN344 is combined with 2,4-thiazolidinedione.
5-(2-methylpiperazine-1-sulfonyl)isoquinolineThe therapeutic efficacy of NN344 can be increased when used in combination with 5-(2-methylpiperazine-1-sulfonyl)isoquinoline.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be increased when combined with NN344.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline may increase the hypoglycemic activities of NN344.
8-azaguanineThe metabolism of 8-azaguanine can be increased when combined with NN344.
8-chlorotheophyllineThe metabolism of 8-chlorotheophylline can be increased when combined with NN344.
9-DeazaguanineThe metabolism of 9-Deazaguanine can be increased when combined with NN344.
9-MethylguanineThe metabolism of 9-Methylguanine can be increased when combined with NN344.
AcarboseThe risk or severity of hypoglycemia can be increased when Acarbose is combined with NN344.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
Not Available

References

General References
  1. Klein O, Lynge J, Endahl L, Damholt B, Nosek L, Heise T: Albumin-bound basal insulin analogues (insulin detemir and NN344): comparable time-action profiles but less variability than insulin glargine in type 2 diabetes. Diabetes Obes Metab. 2007 May;9(3):290-9. [PubMed:17391154]
  2. Jonassen I, Havelund S, Ribel U, Plum A, Loftager M, Hoeg-Jensen T, Volund A, Markussen J: Biochemical and physiological properties of a novel series of long-acting insulin analogs obtained by acylation with cholic acid derivatives. Pharm Res. 2006 Jan;23(1):49-55. Epub 2006 Dec 21. [PubMed:16362452]
External Links
PubChem Substance
347909955

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
Not Available
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Classification
Not classified

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Receptor signaling protein tyrosine kinase activity
Specific Function
Receptor tyrosine kinase which mediates the pleiotropic actions of insulin. Binding of insulin leads to phosphorylation of several intracellular substrates, including, insulin receptor substrates (...
Gene Name
INSR
Uniprot ID
P06213
Uniprot Name
Insulin receptor
Molecular Weight
156331.465 Da

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Barnett CR, Wilson J, Wolf CR, Flatt PR, Ioannides C: Hyperinsulinaemia causes a preferential increase in hepatic P4501A2 activity. Biochem Pharmacol. 1992 Mar 17;43(6):1255-61. doi: 10.1016/0006-2952(92)90500-i. [PubMed:1562279]
  2. Pass GJ, Becker W, Kluge R, Linnartz K, Plum L, Giesen K, Joost HG: Effect of hyperinsulinemia and type 2 diabetes-like hyperglycemia on expression of hepatic cytochrome p450 and glutathione s-transferase isoforms in a New Zealand obese-derived mouse backcross population. J Pharmacol Exp Ther. 2002 Aug;302(2):442-50. doi: 10.1124/jpet.102.033553. [PubMed:12130701]

Drug created on October 21, 2007 16:23 / Updated on March 01, 2020 19:30

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