Evofosfamide

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

Identification

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Name
Evofosfamide
Accession Number
DB06091
Type
Small Molecule
Groups
Investigational
Description

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.

Structure
Thumb
Synonyms
Not Available
External IDs
HAP-302 / TH-302
Categories
UNII
8A9RZ3HN8W
CAS number
918633-87-1
Weight
Average: 449.04
Monoisotopic: 446.930667
Chemical Formula
C9H16Br2N5O4P
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

Pharmacology

Indication

Investigated for use/treatment in solid tumors.

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
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

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. [PubMed:18257544]
External Links
ChemSpider
10157061
ChEMBL
CHEMBL260046
Wikipedia
Evofosfamide

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentTumors, Solid1
1CompletedOtherTumors, Solid1
1CompletedTreatmentAcute Lymphoblastic Leukaemias (ALL) / Acute Myelogenous Leukaemia (AML) / Advanced Myelofibrosis / Chronic Chronic myelogenous leukemia / Chronic Lymphocytic Leukaemia (CLL) / High-risk Myelodysplastic Syndrome1
1CompletedTreatmentMalignant Neoplasm of Pancreas / Tumors, Solid1
1CompletedTreatmentArterial hypoxia / Tumors1
1RecruitingTreatmentMalignant Neoplasm of Pancreas / Melanoma / Prostate Cancer / Squamous Cell Carcinoma of the Head and Neck (SCCHN)1
1TerminatedTreatmentMalignant Neoplasm of Pancreas1
1Unknown StatusTreatmentAdvanced Renal Cell Carcinoma / Gastrointestinal Stromal Tumors / Progressive Neuroendocrine Tumors of pancreatic origin1
1WithdrawnTreatmentEsophageal Cancers1
1, 2Active Not RecruitingTreatmentMultiple Myeloma (MM)1
1, 2CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC) / Malignant Neoplasm of Pancreas / Prostate Cancer1
1, 2CompletedTreatmentSoft Tissue Sarcoma (STS)1
2Active Not RecruitingTreatmentGlioblastomas1
2Active Not RecruitingTreatmentMetastatic Melanoma1
2Active Not RecruitingTreatmentNeoplasms, Pancreatic / Neuroendocrine Tumors1
2CompletedTreatmentAdenocarcinoma of the Pancreas1
2CompletedTreatmentHigh Grade Glioma (HGG)1
2TerminatedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
2TerminatedTreatmentSoft Tissue Sarcoma (STS)1
3CompletedTreatmentMetastatic or Locally Advanced Unresectable Pancreatic Adenocarcinoma1
Not AvailableNo Longer AvailableNot AvailableSoft Tissue Sarcoma (STS)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
Not Available

Taxonomy

Classification
Not classified

Drug created on November 18, 2007 11:29 / Updated on November 02, 2018 06:13