(1-Methyl-2-nitro-1H-imidazol-5-yl)methyl N,N′-bis(2-bromoethyl)phosphorodiamidate
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(1-Methyl-2-nitro-1H-imidazol-5-yl)methyl N,N′-bis(2-bromoethyl)phosphorodiamidate
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CAS No:
918633-87-1
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Formula:
C9H16Br2N5O4P
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Chemical Name:
(1-Methyl-2-nitro-1H-imidazol-5-yl)methyl N,N′-bis(2-bromoethyl)phosphorodiamidate
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Synonyms:
Phosphorodiamidic acid,N,N′-bis(2-bromoethyl)-,(1-methyl-2-nitro-1H-imidazol-5-yl)methyl ester;(1-Methyl-2-nitro-1H-imidazol-5-yl)methyl N,N′-bis(2-bromoethyl)phosphorodiamidate;TH 302;Evofosfamide;2-Bromo-N-[(2-bromoethylamino)-[(3-methyl-2-nitroimidazol-4-yl)methoxy]phosphoryl]ethanamine
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CAS No:
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.|Evofosfamide is a hypoxia-activated prodrug of the cytotoxin bromo-isophosphoramide mustard (Br-IPM) conjugated with 2-nitroimidazole, with potential antineoplastic activity. When exposed to hypoxic conditions, such as those found in hypoxic tumors, the 2-nitroimidazole moiety of evofosfamide is reduced. This releases the DNA-alkylating Br-IPM moiety, which introduces intra- and inter-strand DNA crosslinks in nearby cells; the crosslinks inhibit both DNA replication and cell division, and may lead to apoptosis of cells in the tumor. The inactive form of the prodrug is stable under normoxic conditions, which may limit systemic toxicity.
(1-Methyl-2-nitro-1H-imidazol-5-yl)methyl N,N′-bis(2-bromoethyl)phosphorodiamidate Basic Attributes
449.04
449.04
8A9RZ3HN8W
DTXSID60238721
C71722
Drug Information
Investigated for use/treatment in solid tumors.
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.
evofosfamide
(1-Methyl-2-nitro-1H-imidazol-5-yl)methyl N,N′-bis(2-bromoethyl)phosphorodiamidate Use and Manufacturing
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
Computed Properties
Molecular Weight:449.04
XLogP3:0.6
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:7
Rotatable Bond Count:9
Exact Mass:448.92862
Monoisotopic Mass:446.93067
Topological Polar Surface Area:114
Heavy Atom Count:21
Complexity:374
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes
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