AZD3409

Identification

Name
AZD3409
Accession Number
DB04893
Type
Small Molecule
Groups
Investigational
Description

AZD3409 is a farnesyl-transferase inhibitor (FAR) indicated for the treatment of solid tumors. Phase I trials were initiated January 2003, and were ongoing as of February 2004. As of February 2007 the development of AZD3409 had been discontinued.

Structure
Thumb
Synonyms
Not Available
External IDs
Not Available
Product Ingredients
Not Available
Approved Prescription Products
Not Available
Approved Generic Prescription Products
Not Available
Approved Over the Counter Products
Not Available
Unapproved/Other Products
Not Available
International/Other Brands
Not Available
Brand mixtures
Not Available
Categories
Not Available
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

For the treatment of solid tumors.

Structured Indications
Not Available
Pharmacodynamics

AZD3409 is a novel, oral, antitumor agent that acts as a prenyl transferase inhibitor. It has potentially broad antitumor activity both as monotherapy and in combination with other anticancer treatments. AZD3409 is a double pro-drug; its metabolism involves conversion to a thiol-ester intermediate, then, intracellularly, to a thiol-acid active species. Phase I trials were initiated January 2003, and were ongoing as of February 2004. Recent studies have shown that AZD3409 is a potent inhibitor of both prostate epithelial cell proliferation and cellular invasion, without an associated bone marrow cellular toxicity.

Mechanism of action

In preclinical studies, AZD3409 achieves up to 90% inhibition of FTase in tumors at well tolerated doses. In enzyme studies AZD3409 is also known to inhibit GGTase-1.

TargetActionsOrganism
UProtein farnesyltransferase subunit betaNot AvailableHuman
UProtein farnesyltransferase/geranylgeranyltransferase type-1 subunit alphaNot AvailableHuman
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

AZD3409 is converted to a thiol-ester intermediate, then, intracellularly, to a thiol-acid active species.

Route of elimination
Not Available
Half life

15–20 hours for the thiol-ester intermediate and 15–30 hours for the active thiol-acid metabolite.

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

Synthesis Reference
Not Available
General References
  1. Cengel KA, Deutsch E, Stephens TC, Voong KR, Kao GD, Bernhard EJ: Radiosensitizing effects of the prenyltransferase inhibitor AZD3409 against RAS mutated cell lines. Cancer Biol Ther. 2006 Sep;5(9):1206-10. Epub 2006 Sep 11. [PubMed:16969121 ]
  2. Maiello MR, D'Alessio A, De Luca A, Carotenuto A, Rachiglio AM, Napolitano M, Cito L, Guzzo A, Normanno N: AZD3409 inhibits the growth of breast cancer cells with intrinsic resistance to the EGFR tyrosine kinase inhibitor gefitinib. Breast Cancer Res Treat. 2007 May;102(3):275-82. Epub 2006 Sep 27. [PubMed:17004112 ]
  3. Streeper R, Campos D, Carrizales G, Stephens TC, Izbicka E: Regulation of tumor signaling pathways by AZD3409 in vitro. Anticancer Res. 2006 Nov-Dec;26(6B):4185-9. [PubMed:17201131 ]
External Links
Not Available
ATC Codes
Not Available
AHFS Codes
Not Available
PDB Entries
Not Available
FDA label
Not Available
MSDS
Not Available

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
SpectrumSpectrum TypeSplash Key

Taxonomy

Classification
Not classified

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Zinc ion binding
Specific Function
Essential subunit of the farnesyltransferase complex. Catalyzes the transfer of a farnesyl moiety from farnesyl diphosphate to a cysteine at the fourth position from the C-terminus of several prote...
Gene Name
FNTB
Uniprot ID
P49356
Uniprot Name
Protein farnesyltransferase subunit beta
Molecular Weight
48773.2 Da
References
  1. Wakeling AE: Inhibitors of growth factor signalling. Endocr Relat Cancer. 2005 Jul;12 Suppl 1:S183-7. [PubMed:16113095 ]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Rab geranylgeranyltransferase activity
Specific Function
Essential subunit of both the farnesyltransferase and the geranylgeranyltransferase complex. Contributes to the transfer of a farnesyl or geranylgeranyl moiety from farnesyl or geranylgeranyl dipho...
Gene Name
FNTA
Uniprot ID
P49354
Uniprot Name
Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha
Molecular Weight
44408.32 Da
References
  1. Wakeling AE: Inhibitors of growth factor signalling. Endocr Relat Cancer. 2005 Jul;12 Suppl 1:S183-7. [PubMed:16113095 ]
Drug created on October 21, 2007 13:25 / Updated on August 17, 2016 12:24