tipifarnib   Click here for help

GtoPdb Ligand ID: 8025

Synonyms: R-115777 | R115777
PDB Ligand
Compound class: Synthetic organic
Comment: Tipifarnib is a non-peptidomimetic competitive farnesyltransferase inhibitor (FTI) [4].
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species

tipifarnib is commercially available from our sponsors

2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 3
Hydrogen bond donors 1
Rotatable bonds 4
Topological polar surface area 65.84
Molecular weight 488.12
XLogP 6.97
No. Lipinski's rules broken 1

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES Clc1ccc(cc1)C(c1cncn1C)(c1ccc2c(c1)c(cc(=O)n2C)c1cccc(c1)Cl)N
Isomeric SMILES Clc1ccc(cc1)[C@](c1cncn1C)(c1ccc2c(c1)c(cc(=O)n2C)c1cccc(c1)Cl)N
InChI InChI=1S/C27H22Cl2N4O/c1-32-16-31-15-25(32)27(30,18-6-9-20(28)10-7-18)19-8-11-24-23(13-19)22(14-26(34)33(24)2)17-4-3-5-21(29)12-17/h3-16H,30H2,1-2H3/t27-/m1/s1
InChI Key PLHJCIYEEKOWNM-HHHXNRCGSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
No information available.
Summary of Clinical Use Click here for help
Tipifarnib has been assessed in Phase 2I clinical trials for acute myeloid leukemia (AML) and advanced pancreatic cancer. Phase 2 trials for breast cancer, glioblastoma, malignant melanoma and non-small cell lung cancer are ongoing. Click here to link to ClinicalTrials.gov's listing of all tipifarnib trials.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Tipifarnib inhibits the prenylation and therefore the membrane tethering capacity of RAS proteins, which are often hyper-activated in cancer. Loss of membrane anchorage leaves the RAS protein free in the cytosol where it is degraded. By reducing activity of RAS oncogenes tipifarnib inhibits cell growth, induces apoptosis, and inhibits angiogenesis [3]. However, the promise of FTIs has not been bourne out in clinical trials [2], perhaps due to redundancy in the system which sees geranylgeranyltransferase taking over the prenylation process, when farnesyltransferase is inhibited.