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Neoplasms

Other Diseases

Nervous System Diseases

Chemical drugs

Small molecule drug

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A glimpse into the focused therapeutic areas

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Most used technologies in drug development

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Most frequently developed targets

Disease Domain	Count

Neoplasms	10
Nervous System Diseases	4
Infectious Diseases	3
Endocrinology and Metabolic Disease	2
Hemic and Lymphatic Diseases	2

Top 5 Drug Type	Count

Chemical drugs	11
Unknown	6
Small molecule drug	2

Top 5 Target	Count

MALT1(Mucosa-associated lymphoid tissue lymphoma translocation protein 1)	2
GLUD1(glutamate dehydrogenase 1)	2
ZEB1(zinc finger E-box binding homeobox 1)	2
ENPP1(Ectonucleotide pyrophosphatase/phosphodiesterase family member 1)	2
NTCP(Sodium/bile acid cotransporter)	2

The p53 Y220C mutation is frequently observed in human cancers. This mutation renders the p53 Y220C unstable at physiological temperatures, leading to a loss of its normal function and promoting tumor development. In this study, a total of eight compounds were designed and synthesized based on the active compound C8. The protein thermal shift assay revealed that both C8-3b and C8-6 exhibited similar activity of C8, with a ΔT_m value of +0.5 °C. Compounds C8-1a, C8-1b, and C8-2b were found to enhance the thermostability of p53 Y220C (ΔT_m: + 1.0 °C), the melting temperature exhibits an enhancement of 0.5 °C over the C8, indicating that these compounds possess the ability to stabilize p53 Y220C. The results of the cell viability assay revealed that C8-1b exhibited selective inhibitory effects on the proliferation of tumor cells harboring the p53 Y220C mutation. Furthermore, we utilized molecular docking and two-dimensional interaction analysis to elucidate the binding mode and key interactions of these compounds with p53 Y220C. Our study suggests that these compounds could potentially serve as lead compounds for enhancing the stability of p53 Y220C, thus providing a rational approach for designing small molecule stabilizers against p53 mutations.

01 Jun 2025·European Journal of Medicinal Chemistry

Structural optimization and discovery of high effective isopropanolamine-based TPS1 inhibitors as promising broad-spectrum fungicide candidates

Article

Author: Shi, Dongmei ; Wang, Dongli ; Qian, Chen ; Jiang, Zhiyang ; Chen, Jinxiu ; Hu, Xinyue ; Yang, Xinling ; Wang, Na ; Liu, Junfeng ; Zhu, Wenya ; Xu, Huan ; Duan, Hongxia ; Xu, Zhijian ; Shi, Jie

To address the growing resistance and environmental issues of existing fungicides, the development of novel broad-spectrum fungicides based on new targets, such as TPS1, has been prioritized. However, related research remains limited. In this study, we optimized our previously reported isopropanolamine-based MoTPS1 inhibitor, j11, by replacing its groups on both sides of its isopropanolamine linker with sulfonamide and 1,2,4-triazole fragments through a fragment replacement combining rational design approach. This approach led to the identification of novel isopropanolamine compounds, including g12, g18, o1, and o3, exhibiting significantly improved TPS1 inhibition compared to j11, with IC₅₀ values against MoTPS1 and BcTPS1 of 8.38-14.73 and 38.70-59.99 μM, respectively. The interaction mechanism research confirmed that hydrogen bonds and salt bridges between the novel isopropanolamine compounds and the Glu396 residue in MoTPS1 were crucial during their interaction. Plant leaf and fruit inoculation experiment revealed that these novel isopropanolamine compounds exhibiting substantial inhibition against MoTPS1 and BcTPS1 significantly suppressed the infection of Magnaporthe oryzae and Botrytis cinerea. Preliminary fungicidal mechanism studies indicated that these novel isopropanolamine compounds disrupted various fungal physiological processes including sporulation, conidia germination, appressorium formation, and turgor pressure accumulation within appressorium, while also causing conidia deformation. The hyphal growth inhibition assay against various plant pathogenic fungi suggested that the novel isopropanolamine compounds such as o1 and o3 held the potential as broad-spectrum fungicide candidates with EC₅₀ values of 2.80-17.55 μg/mL. The toxicological assessment suggested that compounds o1 and o3 had no potential toxicity towards diverse non-target organisms. This study provided a valuable insight for optimizing and developing high effective TPS1 inhibitors to be applied in the control of plant diseases.

01 May 2025·International Journal of Biological Macromolecules

Discovery of multi-chitinase inhibitors cinnamyl thiazolidinone compounds as candidates for insect growth regulators via ligand-based optimization strategies

Article

Author: Tang, Bin ; Shi, Jie ; Zou, Renxuan ; He, Ziqi ; Shen, Lijuan ; Jiang, Zhiyang ; Duan, Hongxia ; Xu, Zhijian ; Fu, Haoyu ; Li, Yan ; Yang, Qing ; Shi, Dongmei

Chitinases are recognized as potential targets to develop novel insecticides to control lepidopteran pests. However, the design and development of effective multi-chitinase inhibitors remains a huge challenge. Based on the backgrounds, in this study, we designed and synthesized a series of cinnamyl-thiazolidinedione compounds as potential inhibitors against OfChtI, OfChtII and OfChi-h, for the first time, by integrating strategies including fragment replacement, 3D QSAR-guided design, and bioelectronic isosteric replacement. Among all synthesized compounds, those displayed substantial activities against three chitinases, such as 5f and 9m, simultaneously demonstrated significant larvicidal activities and growth regulation effects against various lepidopteran pests. Inhibition mechanism studies indicated that the π interactions, hydrophobic stacking, and electrostatic interactions between cinnamyl-thiazolidinone compounds and the conserved aromatic tryptophan and phenylalanine residues, as well as the polar asparagine residues in three chitinases, were crucial for their interactions. Furthermore, the qPCR experiment suggested that cinnamyl-thiazolidinone compounds could regulate the chitin metabolism pathway of Ostrinia furnacalis in vivo. This study provides the first successful example of developing novel multi-chitinase inhibitors through ligand-based optimization strategies, offering promising candidates for controlling lepidopteran pests.

100 Deals associated with Centre for Drug Design & Discovery

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100 Translational Medicine associated with Centre for Drug Design & Discovery

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Pipeline

Pipeline Snapshot as of 08 May 2025

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

Preclinical

19

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Current Projects

Drug(Targets)	Indications	Global Highest Phase

CGAS inhibitor (CD3) ( CGAS )	Inflammation More	Preclinical
ZEB antagonist (CD3) ( ZEB1 )	Solid tumor More	Preclinical
KRAS inhibitors (CD3) ( KRAS )	Solid tumor More	Preclinical
Myeloid Receptor Modulator (CD3) ( TREM1 )	Neoplasms More	Preclinical
MALT1 inhibitors (CD3) ( MALT1 )	Hematologic Neoplasms More	Preclinical