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Tags

Neoplasms

Recombinant polypeptide

Diagnostic radiopharmaceuticals

Radionuclide Drug Conjugates (RDC)

Disease domain score

A glimpse into the focused therapeutic areas

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Most used technologies in drug development

Targets

Most frequently developed targets

Disease Domain	Count

Neoplasms	2

Top 5 Drug Type	Count

Radionuclide Drug Conjugates (RDC)	1
Diagnostic radiopharmaceuticals	1
Recombinant polypeptide	1

Top 5 Target	Count

FGL1(Fibrinogen-like protein 1)	1
PDL1(Programmed death-ligand 1)	1

OBJECTIVESDiabetic gastrointestinal dysfunction (DGD) is a serious complication of diabetic mellitus (DM), affecting the enteric nervous system (ENS), particular enteric glial cells (EGCs). This study aimed to elucidate the effects and underlying molecular mechanisms of hyperglycemic stress on EGCs in in vitro and in vivo models of DM.METHODSIn in vitro studies, enteric glial cell line CRL-2690 was exposed to hyperglycemia stress, and cell viability, cell apoptosis and oxidative damage were assessed. In in vivo studies, STZ-induced diabetic mice were constructed, and cell apoptosis and oxidative damage of EGCs in the duodenum of DM mice were assessed.RESULTSThe results showed that hyperglycemic stress markedly induced oxidative damage of EGCs in in vitro and in vivo models of DM. This damage was found to be dependent on the activation of redoxosomes, which involved the phosphorylation of SRC and Vav2, the up-regulation of active RAC1-GTP, and the activation of NADPH oxidase (NOX). Moreover, inhibitors of redoxosomes, such as the RAC1 inhibitor NSC23766 and the NOX inhibitor VAS2870, effectively mitigated the hyperglycemic stress-induced oxidative damage of EGCs. Additionally, inhibition of p66SHC, a downstream target of redoxosomes, attenuated oxidative damage of EGCs under hyperglycemic stress.DISCUSSIONOur findings suggest that the redoxosomes/p66SHC signaling is involved in the oxidative damage of EGCs during the pathological process of DGD. This signaling cascade may represent a potential therapeutic target for the treatment of DGD.

01 Dec 2024·Bioorganic Chemistry

Synthesis and immunotherapy efficacy of a PD-L1 small-molecule inhibitor combined with its 131I-iodide labelled isostructural compound

Article

Author: Xie, Quan ; Zhu, Junyi ; Qiu, Ling ; Lv, Gaochao ; Gao, Xiaoqing ; Hu, Xin ; Zhang, Nan ; Lin, Jianguo ; Peng, Ying ; Xi, Hongjie

Although antibody-based immune checkpoint blockades have been successfully used in antitumor immunotherapy, the low response rate is currently the main problem. In this work, a small-molecule programmed cell death-ligand (PD-L1) inhibitor, LG-12, was developed and radiolabeled with ¹³¹I to obtain the chemically and biologically identical radiopharmaceutical [¹³¹I]LG-12, which aimed to improve the antitumor effect by combination of LG-12 and [¹³¹I]LG-12. LG-12 showed high inhibitory activity to PD-1/PD-L1 interaction. The results of cell uptake and biodistribution studies indicated that [¹³¹I]LG-12 could specifically bind to PD-L1 in B16-F10 tumors. It could induce immunogenic cell death and the release of high mobility group box 1 and calreticulin. The combination of [¹³¹I]LG-12 and LG-12 could significantly inhibit tumor growth and resulted in enhanced antitumor immune response. This PD-L1 small-molecule inhibitor based combination strategy has great potential for tumor treatment.

18 Sep 2024·Bioconjugate Chemistry

Preclinical Evaluation of a PSMA Aptamer-Based Bifunctional PET and Fluorescent Probe

Article

Author: Lin, Jianguo ; Qiu, Ling ; Peng, Ying ; Liu, Qingzhu ; Kong, Sudong ; Xie, Quan ; Xie, Minhao

100 Deals associated with Jiangsu Institute Of Nuclear Medicine

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100 Translational Medicine associated with Jiangsu Institute Of Nuclear Medicine

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Pipeline

Pipeline Snapshot as of 25 Nov 2024

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

Discovery

1

Preclinical

Other

4

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Current Projects

Drug(Targets)	Indications	Global Highest Phase

68Ga-NODA-CDV-Nb109 ( PDL1 )	Neoplasms More	Preclinical
CN118240024 ( FGL1 )	Neoplasms More	Discovery
Technetium[99m] Trodat-1 ( DAT )	Contrast agents More	Pending
131I-Epidepride ( D2 receptor )	Contrast agents More	Pending
99mTc-TRODAT-1 ( DAT )	Contrast agents More	Pending