rrna synthesis

4-Thiouridine (4-TU) 是一种光活化核糖核苷类似物，广泛用于RNA 分析。

Erythromycin (E-Mycin) 是由放线菌产生的大环内酯类抗生素。它结合细菌的 50S 核糖体亚基，通过阻断转肽和易位反应来抑制 RNA 依赖性蛋白的合成。

CX5461 是一种 rRNA 合成抑制剂，具有口服活性，可抑制 Pol I 驱动的 rRNA 转录。CX5461 激活 DNA 损伤反应，在卵巢癌等肿瘤中具有抗肿瘤活性。

Clindamycin hydrochloride monohydrate（Clindamycin alcoholate）是一种口服蛋白质合成抑制剂，具有在金黄色葡萄球菌中以亚抑制浓度(sub-MICs)抑制毒力因子表达的能力。其抗性来源于50S核糖体亚基（23S rRNA）的抗生素结合位点通过酶促甲基化。此外，Clindamycin hydrochloride monohydrate能显著减少杀白细胞毒素（PVL）、毒性休克-葡萄球菌毒素（TSST-1）或α-溶血素（Hla）的产生。

7-Methylguanosine 5’-diphosphate (7-Methyl-GDP) sodium, a cap analog, can be used in the synthesis of mRNA cap analogues[1]. 7-Methylguanosine 5’-diphosphate sodium inhibits binding of eukaryotic initiation factors to reovirus capped mRNA and complex formation involving uncapped mRNA or 18 S rRNA[1].T. brucei mRNA decapping enzyme (TbDcp2) that cleaves 7-Methylguanosine 5’-diphosphate sodium from capped RNA to generate pRNA, a substrate for TbCe1[2]. [1]. Sonenberg N, et al. Nonspecific effect of m7GMP on protein-RNA interactions. J Biol Chem. 1978;253(19):6630-6632.[2]. Ignatochkina AV, et al. The messenger RNA decapping and recapping pathway in Trypanosoma. Proc Natl Acad Sci U S A. 2015;112(22):6967-6972.

NusB-IN-1 (Compound 22r) is a highly effective bacterial rRNA synthesis inhibitor, administered orally. It exhibits potent antimicrobial activity against MRSA and VRSA [1].

Amikacin disulfate (BAY-416651 sulfate) 是氨基糖苷类抗生素，也是卡那霉素的半合成类似物。它具有杀菌作用，直接作用于 30S 和 50S 细菌核糖体亚基，可抑制蛋白质合成。它对大多数革兰氏阴性细菌都有效。它还抑制易感诺卡氏菌和非结核分枝杆菌引起的感染。

CX-5461 dihydrochloride 是一种有效的、口服具有活力的 Pol I 介导的 rRNA synthesis 抑制剂，能够作用于 HCT-116 细胞 (IC50: 142 nM)，A375 细胞 (IC50: 113 nM) 和 MIA PaCa-2 细胞 (IC50: 54 nM)，对 Pol II 作用较小 (IC50≥25 μM)。

Pidnarulex HCl is the salt form of CX-5461, a first-in-class non-genotoxic small molecule targeted inhibitor of RNA polymerase I (Pol I) that activates the p53 pathway without causing DNA damage. CX-5461 selectively inhibits rRNA synthesis by Pol I in the nucleolus, but does not inhibit mRNA synthesis by RNA Polymerase II (Pol II) and does not inhibit DNA replication or protein synthesis. Inhibition of Pol I results in nucleolar stress and release of ribosomal proteins (RP) from the nucleolus. The RP bind to Mdm2 and liberate p53 to orchestrate apoptosis in cancer cells. CX-5461 demonstrates a favorable preclinical profile, potently and selectively kills cancer cells, demonstrates robust in vivo efficacy in multiple models, and has demonstrated oral bioavailability in multiple species.