Application of Dominant Fragment Hybridization Strategy in Drug Development

Hybridization strategy for dominant fragments

It is a classic drug design method.

01

Development of LSD1 inhibitors

Trans-2-Phenylcyclopropylamine (PCPA) has strong inhibitory activity on monoamine oxidase (MAOs) and can be used to treat depression.

02

Development of Mcl-1 inhibitors

Myeloid leukemia factor-1 is highly expressed in a variety of tumor cells, and has a promoting effect on the abnormal proliferation of tumor cells.

03

Development of NMT inhibitors

Derivatives 6 and 7 obtained through high-throughput screening have strong inhibitory activity on N-myristoyltransferase (NMT).

04

Research and development of anti-HIV-1 drugs

Researchers comparatively analyzed the docking results of derivatives 9 and 10 with HIV-1 non-nucleoside reverse transcriptase and found that carbamate groups are one of the key factors for high-efficiency anti-drug resistance, and derivatives 9 and HIV-1 The X-ray crystal complex of non-nucleoside reverse transcriptase showed that 3,5-dichlorophenyl and amino acid residues can interact through hydrogen bonds.

Later, through molecular docking and hybridization strategies of dominant fragments, other researchers discovered that new pyridine amide and pyridone derivatives have strong inhibitory activity against HIV.

The hybridization strategy based on dominant fragments has the advantages of clear thinking, short development time and low cost in drug design.

references

[1] Ueda R, Suzuki T, Mino K, et al.

[2] Pelz NF, Bian ZG, Zhao B, et al.

[3] Hutton JA.

[4] Liu ZQ, Chen WM, Zhan P, etal.

[5] Chen WM, Zhan P, Rai D, et al.