N,N'-Bis(2-bromoethyl)phosphorodiamidic acid (1-methyl-2-nitro-1H-imidazol-5-yl)methyl ester
- Product Name
- N,N'-Bis(2-bromoethyl)phosphorodiamidic acid (1-methyl-2-nitro-1H-imidazol-5-yl)methyl ester
- CAS No.
- 918633-87-1
- Chemical Name
- N,N'-Bis(2-bromoethyl)phosphorodiamidic acid (1-methyl-2-nitro-1H-imidazol-5-yl)methyl ester
- Synonyms
- TH 302;CS-516;HAP-302;EOS-61724;EVOFOSFAMID;EvofosfaMide;TH-302, >=98%;TH 302; TH302;Evofosfamide(TH 302);TH-302 (Evofosfamide)
- CBNumber
- CB52604209
- Molecular Formula
- C9H16Br2N5O4P
- Formula Weight
- 449.04
- MOL File
- 918633-87-1.mol
N,N'-Bis(2-bromoethyl)phosphorodiamidic acid (1-methyl-2-nitro-1H-imidazol-5-yl)methyl ester Property
- 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)
- pka
- 0.34±0.70(Predicted)
- form
- Solid
- 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 and Precautionary Statements (GHS)
- Symbol(GHS)
-
- Signal word
- Warning
- Hazard statements
-
H302Harmful if swallowed
- Precautionary statements
-
P280Wear protective gloves/protective clothing/eye protection/face protection.
P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.
N-Bromosuccinimide Price
- Product number
- 22195
- Product name
- TH-302
- Purity
- ≥95%
- Packaging
- 1mg
- Price
- $40
- Updated
- 2024/03/01
- Product number
- 22195
- Product name
- TH-302
- Purity
- ≥95%
- Packaging
- 5mg
- Price
- $168
- Updated
- 2024/03/01
- Product number
- 22195
- Product name
- TH-302
- Purity
- ≥95%
- Packaging
- 10mg
- Price
- $276
- Updated
- 2024/03/01
- Product number
- 22195
- Product name
- TH-302
- Purity
- ≥95%
- Packaging
- 25mg
- Price
- $590
- Updated
- 2024/03/01
- Product number
- T338200
- Product name
- TH-302
- Packaging
- 5mg
- Price
- $250
- Updated
- 2021/12/16
N,N'-Bis(2-bromoethyl)phosphorodiamidic acid (1-methyl-2-nitro-1H-imidazol-5-yl)methyl ester Chemical Properties,Usage,Production
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.
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 damage 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
N,N'-Bis(2-bromoethyl)phosphorodiamidic acid (1-methyl-2-nitro-1H-imidazol-5-yl)methyl ester Preparation Products And Raw materials
Raw materials
Preparation Products
N,N'-Bis(2-bromoethyl)phosphorodiamidic acid (1-methyl-2-nitro-1H-imidazol-5-yl)methyl ester Suppliers
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- Country
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View Lastest Price from N,N'-Bis(2-bromoethyl)phosphorodiamidic acid (1-methyl-2-nitro-1H-imidazol-5-yl)methyl ester manufacturers
- Product
- N,N'-Bis(2-bromoethyl)phosphorodiamidic acid (1-methyl-2-nitro-1H-imidazol-5-yl)methyl ester 918633-87-1
- Price
- US $7.00/KG
- Min. Order
- 1KG
- Purity
- 99%
- Supply Ability
- 100kg
- Release date
- 2020-01-02