Evofosfamide

This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

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
Weight
Average: 449.04
Monoisotopic: 446.930667
Chemical Formula
C9H16Br2N5O4P
Synonyms
  • (1-methyl-2-nitro-1H-imidazol-5-YL)methyl N,N'-bis(2-bromoethyl)diamidophosphate
  • (1-methyl-2-nitro-1H-imidazole-5-yl)methyl N,N'-bis(2-bromoethyl) diamidophosphate
  • Evofosfamide
External IDs
  • HAP-302
  • TH-302

Pharmacology

Indication

Investigated for use/treatment in solid tumors.

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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
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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
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
  1. 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]
ChemSpider
10157061
BindingDB
50543112
ChEMBL
CHEMBL260046
ZINC
ZINC000029053729
Wikipedia
Evofosfamide

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentMetastatic or Locally Advanced Unresectable Pancreatic Adenocarcinoma1
3CompletedTreatmentSoft Tissue Sarcoma1
2CompletedTreatmentBile Duct Cancer1
2CompletedTreatmentHigh Grade Glioma (HGG)1
2CompletedTreatmentHigh Grade Glioma: Glioblastoma (GBM)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
PropertyValueSource
Water Solubility0.292 mg/mLALOGPS
logP0.89ALOGPS
logP0.73Chemaxon
logS-3.2ALOGPS
pKa (Strongest Acidic)13.89Chemaxon
pKa (Strongest Basic)-0.14Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count5Chemaxon
Hydrogen Donor Count2Chemaxon
Polar Surface Area111.32 Å2Chemaxon
Rotatable Bond Count10Chemaxon
Refractivity84.79 m3·mol-1Chemaxon
Polarizability34.56 Å3Chemaxon
Number of Rings1Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
Not Available

Drug created at November 18, 2007 18:29 / Updated at July 18, 2023 22:56