drug-drug interactions

Mitotane (NCI-C04933) 是 DDD 的同分异构体和 DDT 的衍生物，可作用于肾上腺皮质癌，有抗癌活性。

Pitavastatin calcium (NK-104) 是一种羟甲基戊二酰-CoA 还原酶抑制剂。它在 HepG2 细胞中抑制乙酸合成胆固醇的IC50为 5.8 nM。它是高效的肝细胞低密度脂蛋白胆固醇受体诱导剂。具有抗癌活性。

DSSeb CrosslinkerDisuccinimidyl sebacate)是一种双NHS酯和可透过细胞膜的胺反应性交联剂，可用于蛋白质交联和研究蛋白-蛋白相互作用。

SJPUT-328 是一种PXR (Pregnane X receptor)激动剂，该受体在药物代谢及药物之间的相互作用方面发挥关键作用。

(E)-2,6-Di-tert-butyl-4-(4-(diethylamino)styryl)pyrylium TFA (Compound 4a) 是一种革兰氏阴性外膜渗透剂，通过靶向 LptA 中的 Met47 来阻断 LptA/LptC 的相互作用，显示出协同抗菌效果。(E)-2,6-Di-tert-butyl-4-(4-(diethylamino)styryl)pyrylium (trifluoromethanesulfonate) 能增强 pol B 对野生型和 MDR A. baumannii 及 E. coli 菌株的活性，可作为耐多药革兰氏阴性菌感染的抗生素辅助剂。

2,5-Dioxopyrrolidin-1-yl 6-acrylamidohexanoate可以作为交联剂将固定基质蛋白于凝胶表面，以增强细胞与基质的相互作用，广泛应用于生物化学实验和药物合成研究。

BNS808 是一种具口服活性的选择性CB1R拮抗剂 (IC50= 0.8 nM)，展现了显著的CB2R选择性且脑渗透性极低。目前，BNS808 正在用于研究肥胖及相关代谢并发症，如代谢功能障碍相关的脂肪肝 (MASLD)。通过降低药物进入中枢神经系统的游离利用率，BNS808 提高了安全性，并通过高血浆结合率最大限度减少药物间相互作用。

BI-9627 hydrochloride 是一种高效的钠氢交换体 1(NHE1)抑制剂，在细胞内 pH 恢复实验与人血小板肿胀实验中，其 IC₅₀值分别为 6 nM 和 31 nM，对 NHE2 的选择性超过 30 倍，且对 NHE3 无明显抑制作用。 BI-9627 hydrochloride 可降低 HTR-8/SVneo 细胞的自噬水平，显著降低人精子的细胞内 pH，并可部分逆转 DMA 的效应，同时，能够延长 KO hiPSC-CM 中 Ca²⁺的恢复时间。 BI-9627 hydrochloride 具有较低的药物相互作用风险，在大鼠与犬体内展现出良好的药代动力学特性，并且在缺血再灌注损伤的离体心脏模型中表现出强效活性

(Iso)-ML399是ML399的异构体，对Menin-MLL(Mixed Lineage Leukemia)蛋白相互作用具有抑制活性（IC50=1.4 µM），可用于生物化学实验和药物合成研究。

Febuxostat Acyl Glucuronide 是强效黄嘌呤氧化酶 (XO) 抑制剂非布司他的主要代谢产物。在生物系统中，非布司他通过尿苷二磷酸葡萄糖醛酸转移酶 (UGT) 的催化作用，在羧酸位点发生葡萄糖醛酸化，生成该酰基结合物。该代谢物的形成是非布司他清除的关键途径之一，对于评估药物的代谢稳定性、潜在的药物相互作用以及在特殊人群(如 UGT 酶多态性个体)中的药代动力学行为具有重要研究价值。

5-Benzyloxygramine 是一种 N 蛋白、蛋白互作的原位稳定剂，具有抗病毒和稳定 N-NTD 蛋白的作用。它能够阻断多巴胺受体，可拮抗 5-HT 对大鼠子宫和兔耳的作用。

N-hydroxy Riluzole is a metabolite of the antiglutamatergic agent riluzole .1It is formed from riluzole predominantly by the cytochrome P450 (CYP) isoform CYP1A2 in human hepatic microsomes. 1.Sanderink, G.J., Bournique, B., Stevens, J., et al.Involvement of human CYP1A isoenzymes in the metabolism and drug interactions of riluzole in vitroJ. Pharmacol. Exp. Ther.282(3)1465-1472(1997)

Imidafenacin metabolite M4 is a metabolite of the muscarinic acetylcholine receptor antagonist imidafenacin.1It is formed from imidafenacin by the cytochrome P450 (CYP) isoform CYP3A4. 1.Kanayama, N., Kanari, C., Masuda, Y., et al.Drug-drug interactions in the metabolism of imidafenacin: Role of the human cytochrome P450 enzymes and UDP-glucuronic acid transferases, and potential of imidafenacin to inhibit human cytochrome P450 enzymesXenobiotica37(2)139-154(2007)

Dolutegravir O-β-D-glucuronide is a metabolite of the HIV integrase inhibitor dolutegravir .1It is formed from dolutegravir primarily by the UDP-glucuronosyltransferase (UGT) isoform UGT1A1in vivobut is also metabolized by UGT1A9 in human liver and kidney microsomes and UGT1A3 in human intestinal microsomes.2,1 1.Liu, S.N., Lu, J.B., Watson, C.J.W., et al.Mechanistic assessment of extrahepatic contributions to glucuronidation of integrase strand transfer inhibitorsDrug Metab. Dispos.47(5)535-544(2019) 2.Reese, M.J., Savina, P.M., Generaux, G.T., et al.In vitro investigations into the roles of drug transporters and metabolizing enzymes in the disposition and drug interactions of dolutegravir, a HIV integrase inhibitorDrug Metab. Dispos.41(2)353-361(2013)

6'7'-Epoxybergamottin is a furanocoumarin found in grapefruit. It is a potent inhibitor of the cytochrome P450 (CYP) isoform CYP3A4 with an IC50 value of 0.30 ppm in a cell-free assay, 0.33 μM in HL7 human liver cells, and 0.22 μM in S9 human intestine cells. It has been studied in the context of drug interactions with grapefruit constituents. It is found in grapefruit juice at concentrations of 0.1-7.4 μM and inhibits the transport of talinolol , a permeability glycoprotein (P-gp/ABCB1) transporter substrate, across Caco-2 cell monolayers (IC50 = 0.7 μM). 6'7'-Epoxybergamottin also has insecticidal properties with a concentration of 5 μg/cm2 leading to 100% mortality of adult olive fruit flies.

Isosilybin (Isosilibinin) 是一种类黄酮，来源于乳蓟；能够抑制CYP3A4诱导(IC50:74 μM)。

KS15是一种cryptochrome(CRY)抑制剂，能够促进G1细胞周期阻滞，增强MCF-7细胞的药物敏感性，对人乳腺癌细胞具有抗肿瘤活性。

Ga(III)protoporphyrin-IX, a model for interporphyrin interactions in malaria pigment, possesses potent antibacterial effects against gram-negative, gram-positive, and acid-fast bacteria. It exhibits high solubility in methanol (MeOH) and serves as a malarial pigment analogue for drug development, as well as a potential antibacterial agent.

Tetradecanedioic acid (Tetradecanedicarboxylate) 是一种长链脂肪酸，属于内源性代谢物的一种。它能够作为有机阴离子转运多肽介导的药物-药物相互作用的候选生物标志物。

Epiberberine 是一种从黄连中得到的生物碱，是AChE 和BChE 抑制剂，和非竞争性BACE1抑制剂。在 3T3-L1 细胞分化早期，它能够下调 Raf/MEK1/2/ERK1/2 和 AMPKα/Akt 信号通路。它具有抗氧化作用，能够清除 ONOO-，可用于阿尔滋海默症和糖尿病的研究。

5-HT7 receptor ligand 1是一种强效、高选择性的 5-HT7 受体配体。它常作为药理学工具用于研究 5-HT7 受体在昼夜节律调控、学习记忆及情绪管理中的作用机制。

LY3154885 是一种口服具有活力的多巴胺 D1 受体正变构调节剂 (PAM)。LY3154885 对药物-药物相互作用 (DDI) 的风险具有改善作用。

Coproporphyrin I dihydrochloride is an appropriate clinical biomarker to recapitulate drug-drug interactions mediated by OATP inhibition.

ARRY-403, also known as AMG-151, is an orally available allosteric glucokinase (GK) activator developed for the treatment of type 2 diabetes mellitus (T2DM). ARRY-403 has many favorable physicochemical characteristics and ADME properties (low potential to cause drug–drug interactions (DDIs). ARRY-403 potently activates human glucokinase (GK) in vitro (EC50 = 79 nM at 5 mM glucose), with an S0.5 = 0.93 mM glucose (ARRY-403 at 5 mM) and Vmax = 134% compared to the no activator control. It possesses good in vitro drug-like properties (aqueous solubility, cell permeability, low low potential for drug-drug interactions, low predicted hepatic clearance), and selectivity against broad panels of receptors and enzymes.