Uramustine

• CAT Number: I004511
• CAS Number: 66-75-1
• Molecular Formula: C8H11Cl2N3O2
• Molecular Weight: 252.1
• Purity: ≥95%
• Target: DNA alkylator/crosslinker
• Solubility: DMSO: ≥ 29 mg/mL
• Storage: Store at -20C
• IC50: 5.1 μM

Uramustine is an antineoplastic agent with of 5.1μM in K562 human leukemia cell line.IC50 value: 5.1 μMTarget: DNA alkylator/crosslinkerUramustine is a chemotherapy drug which belongs to the class of alkylating agents. It is used in lymphatic malignancies such as non-Hodgkin/’s lymphoma. It works by damaging DNA, primarily in cancer cells that preferentially take up the uracil due to their need to make nucleic acids during their rapid cycles of cell division. The DNA damage leads to apoptosis of the affected cells.

Reference

1:J Med Chem. 2002 Aug 15;45(17):3630-8. Design, synthesis, and biological activity of hybrid compounds between uramustine and DNA minor groove binder distamycin A.Baraldi PG,Romagnoli R,Guadix AE,Pineda de las Infantas MJ,Gallo MA,Espinosa A,Martinez A,Bingham JP,Hartley JA, PMID: 12166936 Abstract: The design, synthesis, characterization, DNA binding properties, and cytotoxic activity of a novel series of hybrids, namely, a molecular combination of the natural antibiotic distamycin A and the antineoplastic agent uramustine, are reported, and the structure-activity relationships are discussed. This homologous series 29-34 consisted of the minor groove binder distamycin A joined to uramustine (uracil mustard) by suitable aliphatic carboxylic acid moieties containing a flexible polymethylene chain that is variable in length [(CH(2))(n)(), where n = 1-6). All the hybrid compounds in this series exhibit enhanced activity compared to both distamycin A and uramustine derivatives 22-27 used for conjugation, giving IC(50) values in the range 7.26-0.07 microM following a 1 h exposure of human leukemic K562 cells, with maximal activity shown when n = 6. The distance between the uramustine and distamycin frame is crucial for the cytotoxicity, with compounds having linker lengths of four to six being at least 20-fold more cytotoxic than linker lengths one to three. Taq polymerase stop experiments demonstrated selective covalent binding of uramustine-distamycin hybrids to A/T rich DNA sequences, which was again more efficient with compounds 32-34 with a longer linker length. Two consequences can be derived from our study: (a) the distamycin moiety directs binding to the minor groove of A/T rich DNA sequences and, consequently, is responsible for the alkylation regioselectivity found in footprinting studies; (b) the higher flexibility due to a longer linker between the distamycin and uracil moieties allows the formation of complexes with the mustard moiety situated more deeply in the minor groove and, hence, with better alkylating properties.