evofosfamide   Click here for help

GtoPdb Ligand ID: 8695

Synonyms: compound 3b [2] | TH-302
Compound class: Synthetic organic
Comment: Evofosfamide is a hypoxia-activated prodrug being investigated as an antineoplastic therapeutic (compound 3b in [2]). This compound is related to ifosfamide. Being developed by Threshold Pharmaceuticals.
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 CDK toolkit. 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 5
Hydrogen bond donors 2
Rotatable bonds 10
Topological polar surface area 121.13
Molecular weight 446.93
XLogP 1.15
No. Lipinski's rules broken 0
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.

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Canonical SMILES BrCCNP(=O)(NCCBr)OCc1cnc(n1C)[N+](=O)[O-]
Isomeric SMILES BrCCNP(=O)(NCCBr)OCc1cnc(n1C)[N+](=O)[O-]
InChI InChI=1S/C9H16Br2N5O4P/c1-15-8(6-12-9(15)16(17)18)7-20-21(19,13-4-2-10)14-5-3-11/h6H,2-5,7H2,1H3,(H2,13,14,19)
InChI Key UGJWRPJDTDGERK-UHFFFAOYSA-N
No information available.
Summary of Clinical Use Click here for help
Evofosfamide (TH-302) is being evaluated in Phase 2I clinical trial to assess its efficacy as an antineoplastic agent in soft tissue sarcoma (in combination with doxorubicin) and metastatic or locally advanced unresectable pancreatic adenocarcinoma (in combination with gemcitabine). Phase 1 safety, tolerability, and pharmacokinetic findings for TH-302 have been published [5]. Results from a Phase 2 pancreatic cancer study are reported by Borad et al. (2015) [1].
In late 2015 Threshold Pharmaceuticals reported the failure of two Phase 3 trials to improve overall survival compared to placebo as monotherapy or in combination with another antineoplastic. The company has yet to decide whether to proceed with further development of evofosfamide (see the corporate page for evofosfamide here).
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Evofosfamide undergoes activation selectively within the hypoxic tumour compartment. The active component is di-brominated isophosphamide mustard (Br-IPM; PubChem CID 132324) which acts as a DNA alkylating agent [2]. The rationale for expoliting this mechanism of action is outlined in [3]. It is suggested that combination therapy with evofosfamide alongside additional agents which are active in the normoxic tumour compartment may provide additional anti-cancer efficacy.