Vigabatrin Hydrochloride is a medication used to treat epilepsy and other seizure disorders. It is a derivative of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter in the central nervous system. Vigabatrin Hydrochloride works by increasing the concentration of GABA in the brain, which reduces the occurrence of seizures.
PI-1840 is a potent and selective inhibitor for chymotrypsin-like (CT-L) (IC50 value = 27 ± 0.14 nM) over trypsin-like and peptidylglutamyl peptide hydrolyzing (IC50 values >100 μM) activities of the proteasome.IC50 value: 27 nM(CT-L activities of the proteasome) Target: CT-L inhibitorin vitro: PI-1840 is over 100-fold more selective for the constitutive proteasome over the immunoproteasome. Mass spectrometry and dialysis studies demonstrate that PI-1840 is a noncovalent and rapidly reversible CT-L inhibitor. In intact cancer cells, PI-1840 inhibits CT-L activity, induces the accumulation of proteasome substrates p27, Bax, and IκB-α, inhibits survival pathways and viability, and induces apoptosis. Furthermore, PI-1840 sensitizes human cancer cells to the mdm2/p53 disruptor, nutlin, and to the pan-Bcl-2 antagonist BH3-M6 .in vivo: PI-1840 but not bortezomib suppresses the growth in nude mice of human breast tumor xenografts .
Oliceridine is a synthetic opioid analgesic that was developed to provide pain relief with fewer side effects than traditional opioids. It was approved by the US Food and Drug Administration (FDA) in 2020 for the management of acute pain in adults.
TRV130 Racemate is the racemate form of TRV130, which a novel μ-opioid receptor (MOR) G protein-biased ligand.IC50 value:Target: MOR ligandin vitro: In cell-based assays, TRV130 elicits robust G protein signaling, with potency and efficacy similar to morphine, but with far less β-arrestin recruitment and receptor internalization .in vivo: In mice and rats, TRV130 is potently analgesic while causing less gastrointestinal dysfunction and respiratory suppression than morphine at equianalgesic doses . Compared to morphine, TRV130 (3, 4.5mg) elicited higher peak analgesia (105, 116 seconds latency vs 75 seconds for morphine, P<.02), with faster onset and similar duration of action. More subjects doubled latency or achieved maximum latency (180 seconds) with TRV130 (3, 4.5mg) .
Olmesartan D4 is a derivative of the angiotensin II receptor antagonist, olmesartan medoxomil. It is a potent and selective blocker of the angiotensin II type 1 receptor, which is responsible for regulating blood pressure and fluid balance in the body. Olmesartan D4 has been extensively studied for its potential therapeutic applications in the treatment of hypertension, heart failure, and other cardiovascular diseases.
(+)-Ketoconazole is an imidazole anti-fungal agent, a CYP3A4 inhibitor.Target: CYP3A4(+)-Ketoconazole, an imidazole anti-fungal agent, has often produced features of androgen deficiency including decreased libido, gynecomastia, impotence, oligospermia, and decreased testosterone levels, in men being treated for chronic mycotic infections . (+)-Ketoconazole also is a cytochrome P450 inhibitor .(+)-Ketoconazole (KTZ), on the antischistosomal potential of these quinolines against Schistosoma mansoni infection by evaluating parasitological, histopathological, and biochemical parameters. Mice were classified into 7 groups: uninfected untreated (I), infected untreated (II), infected treated orally with PZQ (1,000 mg/kg) (III), QN (400 mg/kg) (IV), KTZ (10 mg/kg)+QN as group IV (V), HF (400 mg/kg) (VI), and KTZ (as group V)+HF (as group VI) (VII). KTZ plus QN or HF produced more inhibition (P<0.05) in hepatic CYP450 (85.7% and 83.8%) and CYT b5 (75.5% and 73.5%) activities, respectively, than in groups treated with QN or HF alone. This was accompanied with more reduction in female (89.0% and 79.3%), total worms (81.4% and 70.3%), and eggs burden (hepatic; 83.8%, 66.0% and intestinal; 68%, 64.5%), respectively, and encountering the granulomatous reaction to parasite eggs trapped in the liver .Clinical indications: Candida infection; Dermatophytosis; FolliculitisFDA Approved Date:Toxicity: teratogenesis; liver injuries; adrenal gland problems
Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) used in the treatment of non-small cell lung cancer (NSCLC). It is also known by its trade name, Tagrisso. Osimertinib is a potent and selective inhibitor of both EGFR-TKI sensitizing and T790M resistance mutations.