tolerability

Nur77 modulator 1 可与Nur77结合，KD 为 3.58 μM。它上调 Nur77 表达，介导Nur77亚细胞定位，诱导Nur77 依赖的内质网应激和自噬，可导致细胞凋亡，Nur77 modulator 1显示出抗肝癌生物活性。

Apricitabine (SPD754) 是一种具有高选择性和口服活性的HIV-1逆转录酶抑制剂(Ki=0.08μM)，是2′-脱氧-3′-氧-4′-硫代胞苷(dOTC)的(-)对映体 。 Apricitabine 对DNA 聚合酶α、β和γ具有抑制作用，Ki 值分别为300μM、12μM 和112.25μM。Apricitabine 在抗逆转录病毒HIV 感染者中显示出良好的抗逆转录病毒治疗效果，具有良好的耐受性和较低的选择性抗性。

PHA 568487 free base 是一种选择性的 α7 烟碱乙酰胆碱受体激动剂，可用于减缓神经炎症。

ALZ-801 是一种可口服的小分子 β-淀粉样蛋白抗寡聚体和聚集抑制剂，是曲米酸的缬氨酸偶联前药，与母体化合物相比，具有显著改善的 PK 特性和胃肠道耐受性。它是治疗阿尔茨海默病的先进且显著改善的候选药物。

The prostaglandin E receptor 4 (EP4) is one of four G protein-coupled receptors that mediate the actions of prostaglandin E2 . Binding of PGE2 to the EP4 receptor causes an increase in intracellular cyclic AMP, which plays important roles in bone formation and resorption, cancer, and atherosclerosis. KMN-80 is a substituted γ-lactam (pyrrolidinone) derivative of PGE1 that acts as a selective and potent agonist of EP4 with an IC50 value of 3 nM (IC50 = 1.4 μM for EP3 and > 10 μM for all other prostanoid receptors). In functional assays it has been shown to stimulate secreted alkaline phosphatase gene reporter activity in EP4-transfected HEK293 cells with an EC50 value of 0.19 nM, demonstrating >5,000 and 50,000-fold selectivity against EP2 and TP, respectively. KMN-80 can induce the differentiation of bone marrow stem cells from both young and aged rats into osteoblasts in vitro (EC50s = 20 and 153 nM, respectively) and exhibits favorable tolerability up to at least 10 μM, whereas the EP4 agonist L-902,688 is highly cytotoxic at similar concentrations in these cells. KMN-80 has been used to repair calvarial defects in an in vivo rat craniomaxillofacial reconstruction model (rate of reduction in defect size equivalent to BMP-2 treated rats) and to promote bone formation in a rat incisor tooth socket model.

BAY 1214784是一种针对人促性腺激素释放激素受体(hGnRH-R)的高效、选择性口服活性拮抗剂，属于螺二氢吲哚衍生物化合物。该化合物能显著降低血浆促黄体激素水平，最高可达49%，同时显示出较低的药代动力学变异性和良好的耐受性，表现出研究子宫肌瘤的潜力。

ROCK2-IN-5是一种复合型化合物，融合了Rho激酶抑制剂fasudil以及NRF2诱导剂咖啡酸和阿魏酸的结构元素。该化合物展示了优秀的多靶点作用特性和较高的耐受性。ROCK2-IN-5在针对SOD1基因变异型ALS研究中具备应用潜力。

Tinengotinib(替恩戈替尼)是一种多激酶抑制剂，靶向一系列参与癌细胞增殖，血管生成和免疫反应调节的激酶，包括Aurora激酶A B、Janus激酶（JAK1 2）、成纤维细胞生长因子受体（FGFR1 2 3）、血管内皮生长因子受体（VEGFRs）等多种激酶，在多种晚期实体瘤的临床试验中显示出良好的耐受性和初步疗效。

Abraxane（Nab-Paclitaxel）为一种Paclitaxel纳米颗粒与白蛋白结合的制剂，展现出较高的疗效及耐受性。通过利用白蛋白传递Paclitaxel，Abraxane形成优异的药代动力学特性。

Mazdutide (IBI-362; LY-3305677) 是一种具有安全性和耐受性的胃泌酸调节素类似物，用于肥胖和2型糖尿病(T2D)的研究。它同时作为胰高血糖素样肽(GLP-1R)和胰高血糖素受体(GCGR)的共激动剂，表现出长效作用。

PTC258为针对伸长复合体蛋白1基因（ELP1）的特异性口服基因剪接调节剂，能促进ELP1在体外和体内的表达增加，并在小鼠模型中显示出良好的耐受性。

Rimegepant, also known as BMS-927711 and BHV-3000, is a potent, selective, competitive, and orally active calcitonin gene-related peptide (CGRP) antagonist in clinical trials for treating migraines. Rimegepant has shown in vivo efficacy without vasoconstriction effect. BMS-927711 is superior to placebo at several different doses (75 mg, 150 mg, and 300 mg) and has an excellent tolerability profile.

Blonanserin (AD-5423) 是一种有效的5-HT2A 和多巴胺 D2 受体拮抗剂，Ki 为 0.812 和 0.142 nM，是一种非典型的抗精神病试剂。

PIKfyve-IN-4 (Compound 40) 是一种具备口服活性且高选择性的磷脂酰肌醇-3-磷酸 5-激酶 (PIKfyve) 抑制剂，其IC50值为0.60 nM，并且展现出良好的全身耐受性。

Inupadenant is an orally active, highly selective A2A receptor antagonist. Inupadenant is not brain-penetrant. Inupadenant has potent anti-tumor activity[1]. [1]. Laurence Buisseret, et al. Phase 1 trial of the adenosine A2Areceptor antagonist inupadenant (EOS-850): Update on tolerability, and antitumor activity potentially associated with the expression of the A2A receptor within the tumor. Journal of Clinical Oncology. Volume 39, Issue 15_suppl.

PF04929113 (SNX-5422) 是一种合成的新型小分子 Hsp90 抑制剂。作为一种具有强大疗效和耐受性的口服制剂，它被定位为一种突破性疗法，在广泛的癌症中具有广泛的适用性。

AZ0108 is an orally bioavailable, potent PARP1,2,6 inhibitor that potently inhibits centrosome clustering and is suitable for in vivo efficacy and tolerability studies. AZ0108 has been utilized as in vitro tools and in vivo probes to investigate the biological consequences of inhibiting centrosome clustering through PARP enzymes. AZ0108 is more selective in its enzyme inhibition profile and effects on cellular pathways and phenotypes. Specifically, AZ0108 inhibits PARPs 1, 2, and 6 with approximately 100-fold selectivity against PARP3 and TNKS1. Consistent with this lack of potencytowards tankyrase, AZ0108 is not active in a DLD-1 Wnt luciferase reporter assay.

Blonanserin-d5 是 Blonanserin 的氘代化合物。Blonanserin 的 CAS 号为 132810-10-7。Blonanserin 是一种有效的5-HT2A和多巴胺 D2 受体拮抗剂，Ki为 0.812 和 0.142 nM，是一种非典型的抗精神病试剂。

Antitubercular agent-20 是口服具有活力的抗结核剂。Antitubercular agent-20 对 MTB H37Rv 和 MDR-MTB 表现出良好的抗结核效果，其 MIC＜0.016 μg ml。在 BALB c 小鼠中，Antitubercular agent-20 表现出较低的细胞毒性和较好的耐受性。

Lipid M (pKa: 6.75) 可用于递送 mRNA 疫苗，引发强大的免疫反应并提高耐受性。

Mazdutide (IBI-362; LY-3305677) TFA 是一款GLP-1R与GCGR的共激动剂，同时是长效合成胃泌酸调节素类似物。该化合物安全性和耐受性良好，适用于肥胖与T2D研究。

The immunoregulator spleen tyrosine kinase (SYK) is upregulated in cutaneous lupus erythematosus (CLE). This double-blind, multicentre, Phase Ib study evaluated the safety, tolerability, pharmacokinetics, pharmacodynamics and clinical efficacy of the selective SYK inhibitor GSK2646264 in active CLE lesions

Acemetacin (TVX 1322) 是一种非甾体抗炎类的化合物。