dhfr-in-3

DHFR-IN-3 (7-bromoquinazoline-2,4-diamine) 是一种二氢叶酸还原酶 (DHFR) 抑制剂。

EGFR HER2 DHFR-IN-3（compound 4c）是一种针对EGFR和HER2的高效双重抑制剂，其IC50分别为0.138 μM和0.092 μM。该化合物同时对DHFR具有抑制作用，IC50为0.193 M。在生物活性方面，EGFR HER2 DHFR-IN-3能够导致MCF7乳腺癌细胞周期在S期发生阻滞，并进而诱导细胞凋亡。

Brivudine monophosphate is a phosphate ester of Brivudine. Brivudine, also known as bromovinyl-deoxyuridine, is a uridine derivative and nucleoside analog with pro-apoptotic and chemosensitizing properties. In vitro, bromovinyl-deoxyuridine (BVDU) has been shown to downregulate the multifunctional DNA repair enzyme APEX nuclease 1, resulting in the inhibition of DNA repair and the induction of apoptosis. In addition, this agent may inhibit the expression of STAT3 (signal transducer and activator of transcription 3), which may result in the downregulation of vascular endothelial growth factor (VEGF). BVDU has also been found to inhibit the upregulation of chemoresistance genes (Mdr1 and DHFR) during chemotherapy.

DHFR-IN-9（化合物8A）是一种二氢叶酸还原酶（DHFR）抑制剂，通过干扰细胞内嘌呤和胸苷酸的生物合成而影响细胞生长和增殖。该化合物对抗耐甲氧西林金黄色葡萄球菌（MRSA）ATCC 43300展现出显著的抑制效果（IC50=0.25 μg mL），并在全身及大腿感染的小鼠模型中显示出抗感染能力（剂量：2.5 mg kg，5 mg kg；ip）。此外，DHFR-IN-9在乳腺癌小鼠模型中展示了超过紫杉醇（Y-B0015）的抗癌活性（剂量：2.5 mg kg；ip；每3天1次）。

EGFR HER2 DHFR-IN-2 (Compound 4b) 是针对EGFR、HER2和DHFR的三重抑制剂，IC50分别为0.248、0.156、0.138 μM。该化合物对包括Hep G2, HeLa, HEp-2, HCT 116, PC-3, MCF7在内的多种癌细胞系展现出显著的抗癌活性(IC50分别为9.14、7.33、14.18、24.87、20.07、6.16 μM)，并能有效减缓乳腺癌肿瘤的生长。