Molecular docking analysis of MCL-1 inhibitors for breast cancer management.

Myeloid leukemia 1 (MCL-1), a BCL-2 protein family member, acts as an anti-apoptotic protein by interacting with pro-apoptotic BCL-2 proteins. Its overexpression is frequently observed in numerous cancer types including breast cancer, and is closely linked to the initiation and progression of tumors as well as poor prognosis and resistance to therapeutic interventions. Here, a database of 3402 chemicals with established therapeutic activity against various diseases was chosen and systematically screened against the MCL-1 protein. Visual inspection and binding energy analysis revealed that the compounds OSU-03012, Raltitrexed, Ostarine (MK-2866), Dovitinib (TKI-258), and Varespladib (LY315920) had strong binding affinity for the MCL-1 protein. Notably, their binding affinity was higher than that of the control compounds. These compounds exhibited strong interactions with critical amino acid residues of the MCL-1 protein. Furthermore, these compounds shared several common amino acid residue interactions with the control compounds. These findings suggest that these compounds may be useful as MCL-1 inhibitors in the treatment of breast cancer. However, additional experimental validation is required to confirm these findings.

Insights from the molecular docking analysis of GRP78 with natural compound inhibitors in the management of cancers.

Cancer is regarded as one of the world's most serious health issues. Glucose regulated protein (GRP78) exhibits a vital role in the proliferation, invasion, and metastasis of numerous cancer cells. Based on that, this study screened the 390 natural compounds targeting the GRP78 catalytic site. Among them, corynanthin, toyocamycin, and nanaomycin were found to strongly bind with GRP78 and possess the binding affinities of -8.4, -8.9, and -8.7 kcal/mol, respectively. In addition, these compounds interacted with key residues of GRP78 and have several amino acid residues interaction in common with the cocrystal ligand (ATP). Based on physicochemical parameters and ADME evaluations, these compounds were found to have good drug-like properties. These compounds could be used as possible GRP78 inhibitors in the fight against cancers. Albeit, exhaustive experimental studies would be required to confirm the findings described here.

Allelic variance among ABO blood group genotypes in a population from the western region of Saudi Arabia

BACKGROUND: Characterization of the ABO blood group at the phenotype and genotype levels is clinically essential for transfusion, forensics, and population studies. This study elucidated ABO phenotypes and genotypes, and performed an evaluation of their distribution in individuals from the western region of Saudi Arabia. METHODS: One-hundred and seven samples underwent standard serological techniques for ABO blood group phenotype analysis. ABO alleles and genotypes were identified using multiplex polymerase chain reaction, and electrophoretic analysis was performed to evaluate the highly polymorphic ABO locus. RESULTS: A phenotype distribution of 37.4%, 30.8%, 24.3%, and 7.5% was found for blood groups O, A, B, and AB respectively in our study cohort. Genotype analysis identified 10 genotype combinations with the O01/O02 and A102/O02 genotypes being the most frequent with frequencies of 33.6% and 14.95%, respectively. Common genotypes such as A101/A101, A101/A102, A101/B101, B101/B101, and O01/O01 were not detected. Similarly, the rare genotypes, cis-AB01/O02, cis-AB01/O01, and cis-AB01/A102 were not found in our cohort. The most frequently observed allele was O02 (35.98%) followed by the A102 allele (17.76%). Furthermore, our findings are discussed in reference to ABO allele and genotype frequencies found in other ethnic groups. CONCLUSION: The study has a significant implication on the management of blood bank and transfusion services in Saudi Arabian patients.