evofosfamide

Ligand id: 8695

Name: evofosfamide

Structure and Physico-chemical Properties

2D Structure
Calculated Physico-chemical Properties
Hydrogen bond acceptors 6
Hydrogen bond donors 2
Rotatable bonds 10
Topological polar surface area 121.13
Molecular weight 446.93
XLogP 1.5
No. Lipinski's rules broken 0

Molecular properties generated using the CDK

No information available.
Summary of Clinical Use
Evofosfamide (TH-302) is being evaluated in Phase III 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 I safety, tolerability, and pharmacokinetic findings for TH-302 have been published [5]. Results from a Phase II 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
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.