MK-8245 trifluoroacetate is a liver-targeting inhibitor of stearoyl-CoA desaturase (SCD) with IC50 of 1 nM for human SCD1 and 3 nM for both rat SCD1 and mouse SCD1, with anti-diabetic and anti-dyslipidemic efficacy. IC50 value: 1 nM (hSCD1) Target: SCD1 in vitro: MK-8245, a phenoxy piperidine isoxazole derivative, has been identified as a potent and liver-specific SCD inhibitor. It contains a tetrazole acetic acid moiety, which is the key molecule for OATPs recognition and liver-targeting. MK-8245 displays similar potencies against human, rat and mouse SCD1 with IC50 values of 1 nM for human SCD1 and 3 nM for both rat SCD1 and mouse SCD1. MK-8245 exhibits a significant SCD inhibition in the rat hepatocyte assay which contains functional, active OATPs with IC50 of 68 nM, while being only weakly active in the HepG2 cell assay which is devoid of active OATPs with IC50 of ~1 μM. MK-8245 displays highly selective activity for the Δ-5 and Δ-6 desaturases (i.e., >100000 μM vs rat and human Δ5D and Δ6D as assessed in the HepG assay. in vivo: Administration of MK-8245 at 10 mg kg in mice exhibits a tissue distribution profile concentrated in the liver. It shows a liver-to-Harderian gland ratio of 21, suggesting a high degree of liver-targeting compared to a systemically distributed compound with liver-to-Harderian gland ratio of 1.5. Oral dosing of MK-8245 in mice, rats, dogs, and rhesus monkeys demonstrates that MK-8245 is distributed mainly to the liver, with low exposure in tissues associated with potential adverse events. The liver-to-skin ratios are >30:1 in all four species. Administration of MK-8245 to eDIO mice before the glucose challenge improves glucose clearance in a dose-dependent manner with ED50 of 7 mg kg.
CAY10711 is a substituted diamine that produces rapid bactericidal activity against both Gram-positive and Gram-negative bacteria, including methicillin-resistant S. aureus (MRSA) and stationary-phase bacteria. It displays MIC99 values of 2.9, 11.5, 2.9, and 2.9 μM against S. aureus RN4220, P. aeruginosa PAO1, E. coli ANS1, and MRSA 10082B, respectively. CAY10711 reduces biofilm formation and promotes biofilm dispersal in P. aeruginosa. It is synergistic with kanamycin and has limited adverse effects against mammalian cells or C. elegans development, survival, or reproduction.
DNA-PK-IN-3 is a highly potent inhibitor of DNA-PK. This compound exerts a synergistic effect when combined with radiotherapy and chemotherapy, resulting in enhanced therapeutic outcomes and significant inhibition of tumor growth. Furthermore, DNA-PK-IN-3 demonstrates remarkable efficacy in reducing damage to normal cells, effectively minimizing adverse side effects. Due to these compelling properties, DNA-PK-IN-3 holds great potential for cancer research applications[1].
Cerlapirdine, also known as SAM-531, WAY-262,531 and PF-05212365, is a selective, potent, full antagonist of the 5-hydroxytryptamine 6 (5-HT6) receptor. Cerlapirdine has been in clinical development for the treatment of cognitive disorders associated with Alzheimer's disease and schizophrenia. As of 2011, it is in phase II clinical trials, and has demonstrated a trend toward efficacy along with a good side effect profile and no incidence of serious adverse events. It exerts its effects by acting as a selective 5-HT6 receptor antagonist.
Abivertinib, also known as AC0010 and Avitinib, is a third-generation EGFR tyrosine kinase inhibitor and BTK Inhibitor that demonstrated clinical efficacy and manageable adverse events (AEs). Abivertinib inhibits cell proliferation, reduces colony-forming capacity, and induces apoptosis and cell cycle arrest in AML cells, especially those harboring FLT3-ITD mutations. Abivertinib was also found to be more sensitive than ibrutinib in treating AML. Abivertinib may be a promising novel agent for AML, with potential for combination treatment with HHT.
V11294A is a novel PDE4 inhibitor. A single oral 300 mg dose of V11294A administered to healthy volunteers results in plasma concentrations adequate to inhibit activation of inflammatory cells ex vivo, which persists for at least 24 h without any adverse reactions
Clozapine HCl is a tricylic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2A 2C receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent.