Onapristone has been used in trials studying the treatment of Prostate Cancer, Recurrent Prostate Cancer, Metastatic Prostate Cancer, Androgen-independent Prostate Cancer, and Progesterone Receptor Positive Tumor: Max 1 Line of Prior Chemotherapy, no Prior Hormone Therapy.
NMS1116354 is an orally bioavailable cell division cycle 7 homolog (CDC7) kinase inhibitor with potential antineoplastic activity. CDC7 kinase inhibitor NMS-1116354 binds to and inhibits the activity of CDC7, which may result in the inhibition of DNA replication and mitosis, the induction of tumor cell apoptosis, and the inhibition of tumor cell proliferation in CDC7-overexpressing tumor cells. The serine-threonine kinase CDC7 initiates DNA replication by phosphorylating MCM2 (minichromosome maintenance complex component 2) at Ser40 and Ser53. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus).
2-chloro-N-(3-((1,1-dioxidobenzo[d]isothiazol-3-yl)amino)phenyl)acetamide is a chemical compound that has gained significant attention in scientific research due to its potential therapeutic and environmental applications. This paper aims to provide a comprehensive overview of the synthesis, chemical structure, biological activity, and potential applications of this compound.
NMS-E973 is an inhibitor of heat shock protein 90 (HSP90; IC50 = 10 nM in a fluorescence polarization assay). It decreases HER2 protein expression (IC50 = 110 nM) in BT474 breast cancer cells and inhibits the growth of a 16 cancer cell line panel (IC50s = 13-362 nM). NMS-E973 (60 mg/kg, i.v., per day for ten days) reduces tumor growth by 74% in an A2780 xenograft mouse model. It reduces expression of HSP90 client proteins, phosphorylated ERK and AKT, and total AKT in lysates from A2780 tumors. NMS-E973 also completely eradicates MOLM-13 acute myeloid leukemia tumors in a mouse xenograft model. NMS-E973 is a novel, selective and potent inhibitor of heat shock protein 90 (Hsp90). NMS-E973 displays significant efficacy in a human ovarian A2780 xenograft tumor model, with a mechanism of action confirmed in vivo by typical modulation of known Hsp90 client proteins, and with a favorable pharmacokinetic and safety profile. The efficacy profile of NMS-E973 suggests a potential for development in different clinical settings, including tumors that have become resistant to molecular targeted agents, particularly in cases of tumors which reside beyond the blood-brain barrier (BBB).
NMS-P953 is a JAK2 inhibitor, displaying significant tumor growth inhibition in SET-2 xenograft tumor model. NMS-P953 has a mechanism of action confirmed in vivo by typical modulation of known biomarkers, and with a favorable pharmacokinetic and safety profile.
NMS-P118 is an orally bioavailable, potent, and selective inhibitor of poly(ADP-ribose) polymerase 1 (PARP1), which is an enzyme activated by DNA damage and is critical for the repair of DNA single-strand breaks via the base excision repair pathway. NMS-P118 is selective for PARP1 (Kd = 9 nM) over PARP2 (Kd = 1,390 nM). It is efficacious in MDA-MD-436 human breast and Capan-1 human pancreatic cancer mouse xenograft models. NMS-P118 is a potent, orally available, and highly selective PARP-1 inhibitor with excellent ADME and pharmacokinetic profiles and high efficacy in vivo both as a single agent and in combination with Temozolomide in MDA-MB-436 and Capan-1 xenograft models, respectively. NMS-P118 was found to be less myelotoxic in vitro than olaparib (now marketed as Lynparza), a dual PARP-1/-2 inhibitor. NMS-P118 is the PARP-1 selective inhibitor with demonstrated anticancer activity as single agent, as well as in combination.
N,N'-1,3-Phenylenedimaleimide (PDMI) is a synthetic compound that belongs to the class of maleimides. It has gained significant attention in the scientific community due to its potential applications in various fields, including medical, environmental, and industrial research. PDMI has been found to exhibit promising biological activity, making it a potential candidate for drug development.