TP53 mutations at codon 234 are associated with chlorambucil treatment in chronic lymphocytic leukemia was written by Lazarian, Gregory;Theves, Floriane;Hormi, Myriam;Letestu, Remi;Eclache, Virginie;Bidet, Audrey;Cornillet-Lefebvre, Pascale;Davi, Frederic;Delabesse, Eric;Estienne, Marie-Helene;Etancelin, Pascaline;Kosmider, Olivier;Laibe, Sophy;Lode, Laurence;Muller, Marc;Nadal, Nathalie;Naguib, Dina;Pastoret, Cedric;Poulain, Stephanie;Sujobert, Pierre;Veronese, Lauren;Imache, Samia;Lefebvre, Valerie;Cymbalista, Florence;Baran-Marszak, Fanny;Soussi, Thierry;French Innovative Leukemia Organisation. And the article was included in American Journal of Hematology in 2022.Synthetic Route of C16H21Cl2N3O2 The following contents are mentioned in the article:
TP53 aberrations, including somatic mutations of TP53 gene and 17p deletion, are a major predictive factor of resistance to fludarabine based chemotherapy in chronic lymphocytic leukemia (CLL) and remain an adverse prognostic factor in the chemofree era. TP53 mutations typically occur all along the DNA-binding domain of the p53 protein. In this study, we aimed at characterizing the profile of the TP53 variants in CLL, their distributions, and a correlation with clin. data. To this end, we retrospectively analyzed a large collection of 568 CLL-associated TP53 variants in 336 patients compiled from centers affiliated with the French Innovative Leukemia. Organization-CLL. Fluorescence in situ hybridization anal. for del(17p) status was available for 207 patients, of which 108 (52%) harbored a 17p deletion. Based on the IGHV mutation status, most patients belong to a high risk group as 73% (172/236) were IGHV unmutated. In the present study, CLL patients frequently harbored multiple subclones with different TP53 mutations. Interestingly, while mutations at classical TP53 hot spot positions (codons 175, 248, or 273) were observed both as single and associated mutations, we noticed that variants at codon 234 were found mostly in polymutated patients (82% cases), highlighting an important intratumoral heterogeneity in cases harboring this mutation. However, in contrast to the other hot spot mutations such as those at codon 175 or 248, the absence of variants at position 234 in any of the untreated patients in our database. Strongly supports the possibility that this mutation is associated with the mutagenic effect of CLB. This study involved multiple reactions and reactants, such as 4-(5-(Bis(2-chloroethyl)amino)-1-methyl-1H-benzo[d]imidazol-2-yl)butanoic acid (cas: 16506-27-7Synthetic Route of C16H21Cl2N3O2).
4-(5-(Bis(2-chloroethyl)amino)-1-methyl-1H-benzo[d]imidazol-2-yl)butanoic acid (cas: 16506-27-7) belongs to imidazole derivatives. Imidazole is the basic core of some natural products such as histidine, purine, histamine and DNA based structures, etc. Among the different heterocyclic compounds, imidazole is better known due to its broad range of chemical and biological properties. Imidazole is incorporated into many important biological compounds. The most pervasive is the amino acid histidine, which has an imidazole side-chain. Histidine is present in many proteins and enzymes, e.g. by binding metal cofactors, as seen in hemoglobin.Synthetic Route of C16H21Cl2N3O2
Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem