AZD3409

Identification

Generic Name
AZD3409
DrugBank Accession Number
DB04893
Background

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.

Type
Small Molecule
Groups
Investigational
Synonyms
Not Available

Pharmacology

Indication

For the treatment of solid tumors.

Pharmacology
Reduce drug development failure rates
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Contraindications & Blackbox Warnings
Contraindications
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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 AvailableHumans
UProtein farnesyltransferase/geranylgeranyltransferase type-1 subunit alphaNot AvailableHumans
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

Adverse Effects
Adverseeffects
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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
Not Available
Classification
Not classified
Affected organisms
  • Humans and other mammals

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. 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. [Article]
  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. [Article]
  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. [Article]
PubChem Substance
347909841

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount

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

Targets

Drugtargets2
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Kind
Protein
Organism
Humans
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. [Article]
Kind
Protein
Organism
Humans
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. [Article]

Drug created on October 21, 2007 19:25 / Updated on June 12, 2020 16:52