| Identification | Back Directory | [Name]
N,N'-Bis(2-bromoethyl)phosphorodiamidic acid (1-methyl-2-nitro-1H-imidazol-5-yl)methyl ester | [CAS]
918633-87-1 | [Synonyms]
TH 302
CS-516
EOS-61724
EVOFOSFAMID
EvofosfaMide
TH-302, >=98%
TH 302; TH302
Evofosfamide(TH 302)
TH-302 (Evofosfamide)
(1-methyl-2-nitro-1H-imidazol-5-yl)methylN,N'-bis(2-bromoethyl)diamidophosphate
(1-Methyl-2-nitro-1H-imidazol-5-yl)methyl N,N'-bis(2-bromoethyl)phosphorodiamidate
N,N'-Bis(2-bromoethyl)phosphorodiamidic acid (1-methyl-2-nitro-1H-imidazol-5-yl)methyl ester
2-bromo-N-[(2-bromoethylamino)-[(3-methyl-2-nitroimidazol-4-yl)methoxy]phosphoryl]ethanamine
Phosphorodiamidic acid, N,N'-bis(2-bromoethyl)-, (1-methyl-2-nitro-1H-imidazol-5-yl)methyl ester | [Molecular Formula]
C9H16Br2N5O4P | [MDL Number]
MFCD22420822 | [MOL File]
918633-87-1.mol | [Molecular Weight]
449.04 |
| Chemical Properties | Back Directory | [Melting point ]
97-98°C | [Boiling point ]
565.4±60.0 °C(Predicted) | [density ]
1.97 | [storage temp. ]
Hygroscopic, -20°C Freezer, Under inert atmosphere | [solubility ]
DMSO (Slightly), Methanol (Slightly) | [form ]
Solid | [pka]
0.34±0.70(Predicted) | [color ]
Off-White to Pale Yellow | [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) | [InChIKey]
UGJWRPJDTDGERK-UHFFFAOYSA-N | [SMILES]
P(NCCBr)(NCCBr)(OCC1N(C)C([N+]([O-])=O)=NC=1)=O |
| Hazard Information | Back Directory | [Description]
TH-302 is a hypoxia-activated prodrug and DNA alkylating agent with anticancer activity.1 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).1 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.2 | [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 | [in vivo]
Evofosfamide (TH-302) is a hypoxia-activated prodrug known to activate selectively under the hypoxic conditions commonly found in solid tumors. The mean values of normalized Ktrans decrease 69.2% for Evofosfamide (TH-302)-treated mice in Hs766t tumors, decrease 46.1% for Mia PaCa-2 tumors and increase 4.9% in SU.86.86 tumors. Both changes for Hs766t and Mia PaCa-2 treatment groups are statistically significant (P<0.01) when compare to their own control group[2]. A significant reduction in the hypoxic fraction (HF) to 2.1%±4.7% is seen after 95% oxygen breathing (P<0.001), whereas 7% oxygen breathing significantly increase the HF to 29.5%±14.7% (P=0.029). Exposing rhabdomyosarcoma-bearing rats to increasing oxygen conditions abolish the effect of TH-302 and reduce the T4×SV from 20.4±3.5 to 15.3±2.5 days (P=0.007), whereas control animals have an increased T4×SV. Upon combination with radiotherapy, the T4×SV of TH-302-treated tumors decrease from 30.8±5.9 (Evofosfamide (TH-302)+radiotherapy) to 25.7±2.9 days (Evofosfamide (TH-302)+radiotherapy+95% O2)[3]. | [storage]
Store at -20°C | [References]
[1] JIAN-XIN DUAN*. Potent and Highly Selective Hypoxia-Activated Achiral Phosphoramidate Mustards as Anticancer Drugs[J]. Journal of Medicinal Chemistry, 2008, 51 8: 2412-2420. DOI: 10.1021/jm701028q
[2] JESSICA D SUN. Selective tumor hypoxia targeting by hypoxia-activated prodrug TH-302 inhibits tumor growth in preclinical models of cancer.[J]. Clinical Cancer Research, 2012, 18 3: 758-770. DOI: 10.1158/1078-0432.ccr-11-1980 |
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China Langchem Inc.
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