small molecule compounds

Chromium(III) acetate （Chromium acetate） 是一种小分子离子交联剂，是用于合成其他化合物的原料。

Fexaramine 是小分子法尼醇 X 受体 (FXR) 激动剂，EC50为 25 nM，与天然化合物相比，亲和力提高了 100 倍。

Zotiraciclib（又名TG02和SB1317）是一种新型小分子化合物，具有强效的CDK JAK2 FLT3抑制作用。该化合物可通过抑制周期蛋白依赖性激酶9（CDK9），耗竭Myc来治疗能穿越血脑屏障的癌症。Zotiraciclib是正在研究的众多CDK抑制剂之一，其他针对CDK9的化合物，用于治疗急性髓细胞性白血病的还包括alvocidib和atuveciclib。许多癌症中的Myc过表达是一个已知因素，其中80%的胶质母细胞性瘤展现此特性。

DDRI-18 是一种调节 DNA 损伤反应的新型小分子抑制剂，具有增敏活性和抗癌活性，抑制非同源末端连接 (NHEJ) DNA 修复过程，增强抗癌 DNA 损伤化合物的细胞毒性作用。

UMK57 是一种CENP-Ei、MCAK 增强剂，选择性促进 k-MT 附着错误纠正以抑制染色体错误分离的小分子化合物，可以通过破坏有丝分裂过程中动粒微管 (k-MT) 附着的稳定性来提高染色体分离保守性。

Mitochondrial release of cytochrome c triggers apoptosis via the assembly of a multimeric complex including caspase-9, Apaf-1, and other components, sometimes called the apoptosome. Library screens have identified small molecules that activate the apoptosome by binding to one or more of its components. CAY10443 is one such molecule. In a cell free, multi-component assay, it activated caspase-3 with an EC50 of 5 μM. These apoptotic activators represent therapeutic lead compounds for the development of antitumor drugs.

Purfalcamine is an orally active, selective Plasmodium falciparum calcium-dependent protein kinase 1 (PfCDPK1) inhibitor with an IC50 of 17 nM and an EC50 of 230 nM. Purfalcamine has antimalarial activity and causes malaria parasites developmental arrest at the schizont stage[1][2]. Purfalcamine has low activity against Toxoplasma gondii calcium-dependent protein kinase 3 (TgCDPK3)[1]. Purfalcamine (225, 450 nM) has no effect on the parasitemia in the first 32 hours. After about 40 hours, parasite level remains stable and then begins dropping[1]. Purfalcamine inhibits proliferation with EC50s of 171-259 nM for P. falciparum strains (3D7, Dd2, FCB, HB3 and W2), which indicates effectiveness against drug-resistant parasites[1]. Given that the EC50 value for P. falciparum (3D7) is 230 nM, Purfalcamine shows a therapeutic window ranging from 23-fold to 36-fold (EC50s for CHO=12.33 μM, HEp2=7.235 μM, HeLa=7.029 μM and Huh7=5.476 μM)[1]. Purfalcamine (10 mg kg; oral gavage; BID; for 6 days) demonstrates a delay in the onset of parasitemia in treated mice[1]. Purfalcamine (20 mg kg; orally gavage) exhibits a Cmax of 2.6 μM with a half-life of 3.1 hours[1]. Animal Model: Male BALB c mice, 7 weeks of age with the malaria parasite[1] [1]. Nobutaka Kato, et al. Gene expression signatures and small-molecule compounds link a protein kinase to Plasmodium falciparum motility. Nat Chem Biol. 2008 Jun;4(6):347-56. [2]. Rajshekhar Y Gaji, et al. Expression of the essential Kinase PfCDPK1 from Plasmodium falciparum in Toxoplasma gondii facilitates the discovery of novel antimalarial drugs. Antimicrob Agents Chemother. 2014 May;58(5):2598-607.