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Purity: ≥98%
Evofosfamide (TH-302) is potent and selective that has an IC50 of 19 nM. It exhibits 270-fold increased cytotoxicity under hypoxia compared to their potency under aerobic conditions and is stable to cytochrome P450 metabolism. Under hypoxia, TH-302 is selectively potent and liver microsomes tolerate it well. With a high hypoxic selectivity [Hypoxia cytotoxicity ratio (HCR) = 270], replacing the chlorine with bromine in the phosphorus mustard in 3b results in a 10-fold increase in potency. Under N2, TH-302 exhibits strong cytotoxicity against human lung cancer H460 cells and human colon cancer HT29 cells. With an IC90 of 0.1 μM and 0.2 μM, respectively, TH-302 inhibits HT29 cells and H460 cells.
| Targets |
Hypoxia-activated prodrug
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| ln Vitro |
Evofosfamide (TH-302) induces γH2AX and apoptosis. In both p53-proficient and -deficient cells, evofosfamide exhibits comparable hypoxia-selective, concentration-dependent cytotoxic activity. Evofosfamide (TH-302) therapy alone results in an accumulation of G2/M cells. Chk1 inhibition by PF47736 in cells treated with evofosfamide reduces evofosfamide (TH-302)-mediated G2/M arrest in both normoxia and hypoxia[1].
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| ln Vivo |
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| Cell Assay |
Evofosfamide (TH-302) and either PF477736 or AZD7762 at a concentration of 0.1 μM are administered to cells for 2 hours in either normoxia (21% O2) or hypoxia (N2). Cells are cultured for an additional 22 hours after being washed in the presence of a Chk1 inhibitor under normoxic conditions. Cell cycle reagent and Guava flow cytometry are used to determine the cell cycle distribution after cells are fixed in 75% ethanol. HT-29 cells are exposed to Evofosfamide (TH-302)e (8 nM, 40 nM, 200 nM, 1 μM, and 5 μM) and 0.1 μM of AZD7762 for 2 h under either normoxia (21% O2) or hypoxia (N2). Following a wash, cells are continuously cultured for an additional 46 hours with 0.1 μM of AZD7762. Caspase activity is measured using a luminescence-based assay[1].
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| References |
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| Molecular Formula |
C9H16BR2N5O4P
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| Molecular Weight |
449.04
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| Exact Mass |
446.93067
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| Elemental Analysis |
C, 24.07; H, 3.59; Br, 35.59; N, 15.60; O, 14.25; P, 6.90
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| CAS # |
918633-87-1
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| Related CAS # |
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| Appearance |
Solid powder
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| SMILES |
CN1C(=CN=C1[N+](=O)[O-])COP(=O)(NCCBr)NCCBr
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| InChi Key |
UGJWRPJDTDGERK-UHFFFAOYSA-N
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| InChi Code |
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)
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| Chemical Name |
2-bromo-N-[(2-bromoethylamino)-[(3-methyl-2-nitroimidazol-4-yl)methoxy]phosphoryl]ethanamine
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2270 mL | 11.1349 mL | 22.2697 mL | |
| 5 mM | 0.4454 mL | 2.2270 mL | 4.4539 mL | |
| 10 mM | 0.2227 mL | 1.1135 mL | 2.2270 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT00495144 | Completed | Drug: TH-302 | Tumors Hypoxia |
Threshold Pharmaceuticals | June 2007 | Phase 1 |
| NCT00742963 | Completed | Drug: TH-302 | Soft Tissue Sarcoma | Threshold Pharmaceuticals | August 2008 | Phase 1 Phase 2 |
| NCT01833546 | Completed | Drug: Evofosfamide Drug: Gemcitabine |
Solid Tumor Pancreatic Cancer |
Merck KGaA, Darmstadt, Germany | April 18, 2013 | Phase 1 |
| NCT02342379 | Completed | Drug: TH-302 Drug: Bevacizumab |
Glioblastoma | The University of Texas Health Science Center at San Antonio |
May 2015 | Phase 2 |
| NCT01144455 | Completed | Drug: TH-302 Drug: Gemzar (Gemcitabine) |
Pancreatic Adenocarcinoma | Threshold Pharmaceuticals | June 2010 | Phase 2 |
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