JXL069 是一种最初由加州大学洛杉矶分校(University of California, Los Angeles,UCLA)开发的实验性药物,其作为一种高效且高度选择性的线粒体丙酮酸转运载体(mitochondrial pyruvate carrier,MPC)抑制剂,可有效阻断丙酮酸向线粒体内的受控转运过程,从而重塑细胞能量代谢状态。该化合物在动物模型研究中通过明确的作用机制验证,显示出作为代谢调节剂在雄激素性脱发治疗领域中的潜在应用价值和良好的临床前研究前景。
Desmethyl ranolazine is a metabolite of the antianginal agent ranolazine .1It is formed from ranolazine by the cytochrome P450 (CYP) isoform CYP3A.
1.Wang, Y., Chen, X., Sun, Z., et al.Development and validation of a sensitive LC-MS/MS assay for simultaneous quantitation of ranolazine and its three metabolites in human plasmaJ. Chromatogr. B889-89010-16(2012)
Palonosetron N-oxide is a metabolite of the serotonin (5-HT) receptor subtype 5-HT3antagonist palonosetron .1It is also a potential impurity in palonosetron preparations.2Palonosetron N-oxide is a degradation product formed by exposure to oxidative stress.
1.Stoltz, R.A., Cyong, J.-C., Shah, A., et al.Pharmacokinetic and safety evaluation of palonosetron, a 5-hydroxytryptamine-3 receptor antagonist, in U.S. and Japanese healthy subjectsJ. Clin. Pharmacol.44(5)520-531(2004) 2.Vishnu Murthy, M., Srinivas, K., Kumar, R., et al.Development and validation of a stability-indicating LC method for determining palonosetron hydrochloride, its related compounds and degradation products using naphthalethyl stationary phaseJ. Pharm. Biomed. Anal.56(2)429-435(2011)
5,6-dimethyl-2-Thiouracil is a heterocyclic building block that has been used in the synthesis of anti-HIV-1 pyrimidinones.1 It has also been used as an internal standard for the quantification of thyreostats, including 2-thiouracil, in bovine plasma.2
|1. Navrotskii, M.B. Synthesis and anti-HIV-1 activity of new 2-[(2-phthalimidoethyl)thio]-4(3H)-pyrimidinone derivatives. Pharm. Chem. J. 39(9), 466-467 (2005).|2. Schmidt, K.S. In-house validation and factorial effect analysis of a liquid chromatography-tandem mass spectrometry method for the determination of thyreostats in bovine blood plasma. Anal. Bioanal. Chem. 406(3), 735-743 (2014).
O-desmethyl Brinzolamide is an active metabolite of the carbonic anhydrase (CA) inhibitor brinzolamide .1,2It inhibits CAII and CAIV (IC50s = 0.136 and 165 nM, respectively).1
1.Huang, Q., Rui, E.Y., Cobbs, M., et al.Design, synthesis, and evaluation of NO-donor containing carbonic anhydrase inhibitors to lower intraocular pressureJ. Med. Chem.58(6)2821-2833(2015) 2.Lo Faro, A.F., Tini, A., Gottardi, M., et al.Development and validation of a fast ultra-high-performance liquid chromatography tandem mass spectrometry method for determining carbonic anhydrase inhibitors and their metabolites in urine and hairDrug Test Anal.13(8)1552-1560(2021)
PSB-KD477 is an Agonist of the Cannabinoid-Activated Orphan G-Protein-Coupled Receptor GPR18. PSB-KD477 displayed significantly higher potency and efficacy than THC, determined in a GPR18-dependent β-arrestin recruitment assay, and were found to be selective versus the CB-sensitive receptors CB1, CB2, and GPR55. Structure-activity relationships were steep, and indole substitution was crucial for biological activity. These first selective agonists, which are structurally distinct from the lipidic agonist(s), will allow target validation studies and may eventually contribute to the deorphanization of GPR18.
Ritlecitinib, also known as PF-06651600, is a potent and selective JAK3 inhibitor. PF-06651600 is a potent and low clearance compound with demonstrated in vivo efficacy. The favorable efficacy and safety profile of this JAK3-specific inhibitor PF-06651600 led to its evaluation in several human clinical studies. JAK3 was among the first of the JAKs targeted for therapeutic intervention due to the strong validation provided by human SCID patients displaying JAK3 deficiencies.
PFI-6 is a selective and non-cytotoxic probe targeting the YEATS domain of MLLT1 (ENL/YEATS1) and MLLT3 (AF9/YEATS3), with IC50 values of 140 nM for MLLT1 and 160 nM for MLLT3. It serves as a molecular tool to investigate the role of MLLT1/3 in diseases and genome validation studies [1].