Chemical Property of Evofosfamide
Chemical Property:
- Boiling Point:565.4±60.0 °C(Predicted)
- PKA:0.34±0.70(Predicted)
- PSA：123.81000
- Density:1.97
- LogP:3.22700
- Storage Temp.:Hygroscopic, -20°C Freezer, Under inert atmosphere
- Solubility.:DMSO (Slightly), Methanol (Slightly)
- XLogP3:0.6
- Hydrogen Bond Donor Count:2
- Hydrogen Bond Acceptor Count:7
- Rotatable Bond Count:9
- Exact Mass:448.92862
- Heavy Atom Count:21
- Complexity:374
- Purity/Quality:
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99%, *data from raw suppliers
TH-302 *data from reagent suppliers
Safty Information:
- Pictogram(s):
- Hazard Codes:
- MSDS Files:
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SDS file from LookChem
Useful:
- Canonical SMILES:CN1C(=CN=C1[N+](=O)[O-])COP(=O)(NCCBr)NCCBr
- Recent ClinicalTrials:A Phase 2 Biomarker - Enriched Study of TH-302 in Subjects With Advanced Melanoma
- Recent EU Clinical Trials:A phase II trial to assess the activity and safety of TH-302 in combination with sunitinib in patients with well- and moderately-differentiated metastatic pancreatic neuroendocrine tumors (pNET) previously untreated
- Recent NIPH Clinical Trials:A Phase II, Single-arm, Japanese Multicenter Trial of TH-302 in Combination with Doxorubicin in Subjects with Locally Advanced Unresectable or Metastatic Soft Tissue Sarcoma(EMR 200592-008)
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Description
TH-302 is a hypoxia-activated prodrug and DNA alkylating agent with anticancer activity. It is selectively cytotoxic to H460 human non-small cell lung cancer (NSCLC) cells grown under hypoxic over normoxic conditions (IC50s = 0.019 and 5.1 μM, respectively). Under hypoxic conditions, TH-302 undergoes a one-electron reduction to form an active radical intermediate that is then further reduced to form a DNA-intercalating hydroxylamine. Under normoxic conditions, the radical intermediate is quenched and induces reformation of the inactive nitroazole prodrug. TH-302 reduces survival of H460 and HT-29 cells in a clonogenic assay (IC50s = 0.2 and 0.2 μM, respectively). In vivo, TH-302 (33 mg/kg per day) inhibits primary tumor growth by 41% in an MIA PaCa-2-RFP mouse orthotopic xenograft model. It inhibits tumor growth by greater than 40% in Calu-6 NSCLC, H82 small cell lung, A375 melanoma, PC-3 prostate, and BxPC-3 pancreatic cancer mouse xenograft models when administered at 50 mg/kg.
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Uses
TH-302 is a 2-nitroimidazole triggered hypoxia-activated prodrug (HAP) of bromo-isophosphoramide mustard. Studies have shown that TH-302 treatment exhibited hypoxia-selective cytotoxicity and DNA dama
ge in human cancer cell TH-302 is a 2-nitroimidazole triggered hypoxia-activated prodrug (HAP) of bromo-isophosphoramide mustard. Studies have shown that TH-302 treatment exhibited hypoxia-selective cytotoxicity and DNA damage in human cancer cell
