Identification
- Generic Name
- Evofosfamide
- DrugBank Accession Number
- DB06091
- Background
TH-302 is a novel cancer therapeutic specifically activated under the low oxygen or "hypoxic" conditions typical of solid tumor cancer cells. TH-302 is a nitroimidazole-linked prodrug of a brominated derivative of an isophosphoramide mustard previously used in cancer drugs such as ifosfamide, cyclophosphamide, and glufosfamide. TH-302 has been shown, in preclinical studies, to be both efficacious and well tolerated.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
Structure for Evofosfamide (DB06091)
- Weight
- Average: 449.04
Monoisotopic: 446.930667 - Chemical Formula
- C9H16Br2N5O4P
- Synonyms
- Evofosfamide
- External IDs
- HAP-302
- TH-302
Pharmacology
- Indication
Investigated for use/treatment in solid tumors.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Contraindications & Blackbox Warnings
Avoid life-threatening adverse drug eventsImprove clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events & improve clinical decision support.- Pharmacodynamics
Not Available
- Mechanism of action
TH-302 combines a 2-nitroimidazole oxygen-sensing trigger with a masked DNA crosslinker. Upon activation in oxygen deficient zones, TH-302 is converted selectively to the drug's active form, dibromo isophosphoramide mustard, a potent alkylator. TH-302 targets levels of severe hypoxia that are found in tumors but are rare in normal tissues - this is how selective targeting of the tumor occurs. After conversion to the active form of the drug, the hypoxic cells are exposed to high concentrations of released cytotoxic agent, which can also diffuse into the adjacent regions of the tumor.
- Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.Improve decision support & research outcomes with our structured adverse effects data.- 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
- Classification
- Not classified
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 8A9RZ3HN8W
- CAS number
- 918633-87-1
- InChI Key
- UGJWRPJDTDGERK-UHFFFAOYSA-N
- 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)
- IUPAC Name
- (2-bromoethyl)({[(2-bromoethyl)amino][(1-methyl-2-nitro-1H-imidazol-5-yl)methoxy]phosphoryl})amine
- SMILES
- CN1C(COP(=O)(NCCBr)NCCBr)=CN=C1[N+]([O-])=O
References
- General References
- Duan JX, Jiao H, Kaizerman J, Stanton T, Evans JW, Lan L, Lorente G, Banica M, Jung D, Wang J, Ma H, Li X, Yang Z, Hoffman RM, Ammons WS, Hart CP, Matteucci M: Potent and highly selective hypoxia-activated achiral phosphoramidate mustards as anticancer drugs. J Med Chem. 2008 Apr 24;51(8):2412-20. doi: 10.1021/jm701028q. Epub 2008 Feb 8. [Article]
- External Links
- ChemSpider
- 10157061
- ChEMBL
- CHEMBL260046
- ZINC
- ZINC000029053729
- Wikipedia
- Evofosfamide
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 3 Completed Treatment Metastatic or Locally Advanced Unresectable Pancreatic Adenocarcinoma 1 3 Completed Treatment Soft Tissue Sarcoma 1 2 Completed Treatment Cancer of the Biliary Tract 1 2 Completed Treatment Glioblastoma Multiforme (GBM) 1 2 Completed Treatment High Grade Glioma (HGG) 1 2 Completed Treatment Neuroendocrine Tumors / Pancreatic Neoplasms 1 2 Completed Treatment Pancreatic Adenocarcinoma 1 2 Terminated Treatment Metastatic Melanoma 1 2 Terminated Treatment Non-Small Cell Lung Cancer, Lung Cancer, Cancer 1 2 Terminated Treatment Soft Tissue Sarcoma 1
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
Property Value Source Water Solubility 0.292 mg/mL ALOGPS logP 0.89 ALOGPS logP 0.73 Chemaxon logS -3.2 ALOGPS pKa (Strongest Acidic) 13.89 Chemaxon pKa (Strongest Basic) -0.14 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 111.32 Å2 Chemaxon Rotatable Bond Count 10 Chemaxon Refractivity 84.79 m3·mol-1 Chemaxon Polarizability 34.56 Å3 Chemaxon Number of Rings 1 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Not Available
Drug created at November 18, 2007 18:29 / Updated at February 21, 2021 18:51