Delving into the Latest Updates on NSC23766 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

NSC23766

Target

RAC1 x TIAM1

Action

inhibitors

Mechanism

RAC1 inhibitors(Rac family small GTPase 1 inhibitors), TIAM1 inhibitors(TIAM Rac1 associated GEF 1 inhibitors)

Therapeutic Areas

NeoplasmsUrogenital Diseases

Active Indication

Prostatic HyperplasiaProstatic Cancer

Inactive Indication-

Originator Organization

Children's Hospital Research Foundation

Active Organization

Texas Tech University Health Sciences CenterChildren's Hospital Research Foundation

Inactive Organization-

License Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Structure/Sequence

Molecular FormulaC24H35N7

InChIKeyDEFBCZWQLILOJF-UHFFFAOYSA-N

CAS Registry733767-34-5

Platelet function during inflammation is dependent on activation by endogenous nucleotides acting on purinergic receptors. The P2Y14 receptor has been reported to be expressed on platelets and is involved in leukocyte recruitment during inflammation. However, a role for P2Y14 receptors in platelet function has not yet been determined.

Experimental Approach:

Platelets obtained from healthy human volunteers were incubated with the P2Y14 receptor agonist, UDP‐Glucose (UDP‐G), and PPTN, a selective P2Y14 receptor antagonist. Platelet activation was quantified using Ca2+ mobilization, aggregation and chemotaxis assays. Cooperativity with P2Y1 receptor activation was also assessed after stimulation with UDP‐G in the presence of MRS2500, a selective P2Y1 receptor antagonist.

Key Results:

Ca2+ mobilization occurred in platelets after incubation with UDP‐G in a concentration‐dependent manner, and this was suppressed in platelets treated with PPTN. Platelets did not aggregate, or bind to fibrinogen after incubation with UDP‐G. However, platelet chemotaxis towards f‐MLP was dependent on P2Y14 receptor stimulation with UDP‐G and this was reduced by Rho‐GTPase inhibitors. Furthermore, UDP‐G‐induced Ca2+ mobilization and chemotaxis were also inhibited when platelets were pretreated with MRS2500. Conversely, ADP‐induced Ca2+ mobilization, chemotaxis and aggregation were not affected by the incubation with PPTN.

Conclusion and Implications:

Platelets can be activated via P2Y14 receptor stimulation to induce chemotaxis but not aggregation. Furthermore, this was dependent on concomitant activation of P2Y1 receptor. Activation of P2Y14 receptors on platelets may therefore be relevant during inflammation, but cooperation with P2Y1 receptor activation is required.

01 Jun 2025·Translational Cancer Research

The effect and related mechanisms of RAC1 GTP on radiotherapy for hepatocellular carcinoma

Article

Author: Chou, Jianbo ; Lu, Yi ; Xu, Xiaoyu ; Jiang, Wei ; Fang, Zhengxuying

Background:

Ras-related C3 botulinum toxin substrate 1 (RAC1), a pivotal Rho guanosine triphosphatases (GTPase) implicated in oncogenic processes and radiotherapeutic resistance across malignancies, has not been extensively examined within the context of hepatocellular carcinoma (HCC) radiotherapy. Therefore, this study aimed to evaluate the expression and prognostic significance of RAC1 in HCC, investigate the molecular mechanisms by which radiation-induced RAC1 GTPase activity mediates radioresistance, and validate targeted inhibition of this activity as a potential strategy to enhance HCC radiosensitivity.

Methods:

RAC1 expression was assessed in HCC versus adjacent tissues via The Cancer Genome Atlas (TCGA) and immunohistochemical (IHC) staining of clinical specimens. Its prognostic significance was rigorously evaluated using Cox regression models and visualized via nomogram construction. Radiation-induced RAC1 GTP activity in MHCC97-H cells was quantified by G-protein-linked immunosorbent assay (G-LISA), with downstream signaling (p-IκBα/Bcl-xL) and cell cycle dynamics analyzed via Western blotting and flow cytometry. NSC23766, a RAC1 GTP inhibitor, was employed to identify the pathway-specific effects.

Results:

RAC1 exhibited marked overexpression in HCC tissues, correlating with advanced pathological stages and inferior prognosis. Radiation triggered RAC1 GTP activation in MHCC97-H cells, driving p-IκBα/Bcl-xL antiapoptotic signaling and G2/M arrest. NSC23766 suppressed radiation-induced IκBα phosphorylation (P<0.05), Bcl-xL upregulation, and cell cycle arrest attenuating radioresistance.

Conclusions:

RAC1 overexpression portends poor HCC prognosis and mediates radioresistance through GTP-dependent activation of antiapoptotic pathways and cell cycle modulation. Targeting RAC1 GTP activity may enhance the radiosensitivity of HCC.

01 Dec 2024·VIROLOGY

The actin cytoskeleton is important for pseudorabies virus infection

Article

Author: Wang, Jin-Yuan ; Wan, Bo ; Wang, Jiang ; Pan, Jia-Jia ; Xu, Kun ; Wang, Xiao-Han ; Guo, Jie-Yuan ; Li, Xin-Man ; Chu, Bei-Bei ; Yang, Guo-Yu ; Zeng, Lei ; Hao, Wen-Bo

Viruses are dependent on the host factors for their replication and survival. Therefore, identification of host factors that druggable for antiviral development is crucial. The actin cytoskeleton plays an important role in the virus infection. The dynamics change of actin and its function are regulated by multiple actin-associated proteins (AAPs). However, the role and mechanism of various AAPs in the life cycle of virus are still enigmatic. In this study, we analyzed the roles of actin and AAPs in the replication of pseudorabies virus (PRV). Using a library of compounds targeting AAPs, our data found that multiple AAPs, such as Rho-GTPases, Rock, Myosin and Formin were involved in PRV infection. Besides, our result demonstrated that the actin-binding protein Drebrin was also participated in PRV infection. Further studies are necessary to elucidate the molecular mechanism of AAPs in the virus life cycle, in the hope of mining host factors for antiviral developments.

100 Deals associated with NSC23766

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