Delving into the Latest Updates on NHWD-870 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

BET

Mechanism

BET inhibitors(Bromodomain and extra terminal domain protein inhibitors)

Therapeutic Areas

NeoplasmsImmune System DiseasesHemic and Lymphatic Diseases+ [3]

Active Indication

Advanced NUT CarcinomaDiffuse Large B-Cell LymphomaNon-Hodgkin Lymphoma+ [6]

Inactive Indication-

Originator Organization

Ningbo Wenda Pharmaceutical Technology Co., Ltd

Active Organization

Ningbo Wenda Pharmaceutical Technology Co., Ltd

Inactive Organization-

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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BackgroundNuclear protein in testis (NUT) carcinoma (NC) is a rare, highly aggressive neoplasm, usually accompanying with NUTM1 (NUT midline carcinoma family member 1) gene fusions. Primary thyroid NC is clinically rare and to date there is no established treatment guideline available for NC. We report a case of histopathologically confirmed thyroid NC and provide reference for diagnosis and treatment.Case DescriptionWe presented a 32-year-old female admitted to hospital with "painful neck swelling and progressive dysphagia". Preoperative ultrasound-guided core needle aspiration biopsy suggested a poorly differentiated tumor. Considering the tumor was totally unresected on computed tomography (CT) scan, a partial thyroidectomy was performed to obtain sufficient tissue for a clear diagnosis. Histopathological specimens showed features of sudden keratosis. Strong immunoreactivity with NUT was detected by immunohistochemistry (IHC) and thus confirmed the diagnosis of NC. CK5/6, P40 and P63 were partially positive exclusively in keratosis area. Next-generation sequencing (NGS) and RNA sequencing results revealed a NSD3-NUTM1 fusion. The patient was treated with a combined regimen of radiotherapy of 70 Gy, chemotherapy with paclitaxel (albumin-bound), immunotherapy with nivolumab, targeted therapy with anlotinib and BET inhibitor NHWD-870, but the patient died 7 months after diagnosis.ConclusionsThyroid NC is a rare and distinct pathological subset of NUT carcinoma with a higher rate of NSD3-NUTM1 fusion. In the clinical diagnosis process, we recommended performing NUT IHC for poorly differentiated thyroid tumors. Gene rearrangement detection is also helpful for diagnosis and treatment. At present, surgery and radiation are still first choices for NC, and advances in targeted immunotherapy such as bromodomain and end motif inhibitors (BETi) may bring better treatment options to patients.

01 Apr 2024·European Journal of Pharmacology

A BET inhibitor, NHWD-870, can downregulate dendritic cells maturation via the IRF7-mediated signaling pathway to ameliorate imiquimod-induced psoriasis-like murine skin inflammation

Article

Author: Jin, Liping ; Chen, Xiang ; Pei, Shiyao ; Dong, Liang ; Chen, Wangqing ; Yin, Mingzhu ; Kuang, Yehong ; Zhu, Wu

Psoriasis is a chronic, recurrent, inflammatory dermatosis accompanied by excessive activation of dendritic cells (DCs), which are primarily responsible for initiating an immune response. The bromodomain and extraterminal domain (BET) family plays a pivotal role in the transcriptional regulation of inflammation and its inhibitors can downregulate DCs maturation and activation. Here we investigated the effect of NHWD-870, a potent BET inhibitor, on inflammation in an imiquimod (IMQ)-induced psoriasis-like mouse model and murine bone marrow-derived dendritic cells (BMDCs) stimulated by lipopolysaccharide (LPS) and IMQ. Application of NHWD-870 significantly ameliorated IMQ-triggered skin inflammation in mice, and markers associated with DC maturation (CD40, CD80 and CD86) were decreased in skin lesions, spleen and lymph nodes. Additionally, NHWD-870 reduced LPS or IMQ induced DCs maturation and activation in vitro, with lower expression of inflammatory cytokines [interleukin (IL)-12, IL-23, tumor necrosis factor-α, IL-6, IL-1β, chemokine (C-X-C motif) ligand (CXCL)9 and CXCL10]. In addition, we found that interferon regulatory factor 7 (IRF7) significantly increased during DCs maturation, and inhibition of IRF7 could impair BMDCs maturation and activation. What's more, IRF7 was highly expressed in both psoriatic patients and IMQ-induced psoriasis-like mice. Single-cell RNA sequencing of normal and psoriatic skin demonstrated that IRF7 expression was increased in DCs of psoriatic skin. While NHWD-870 could inhibit IRF7 and phosphorylated-IRF7 expression in vivo and in vitro. These results indicate that NHWD-870 suppresses the maturation and activation of DCs by decreasing IRF7 proteins which finally alleviates psoriasis-like skin lesions, and NHWD-870 may be a potent therapeutic drug for psoriasis.

01 Feb 2024·Experimental Eye Research

IL1R2 promotes retinal angiogenesis to participate in retinopathy of prematurity by activating the HIF1α/PFKFB3 pathway

Article

Author: Li, Qiaolian ; Liu, Li ; Zhou, Na

Retinopathy of prematurity (ROP) is the leading cause of blindness in children, but there is no safe and effective treatment available. Interleukin-1 receptor type 2 (IL1R2) acts as a decoy receptor for IL-1 may affect ROP progression. This study aimed to investigate the role of IL1R2 in ROP. A microglial cell model was established under hypoxia conditions and co-cultured with choroidal endothelial cells, while an oxygen-induced retinopathy (OIR) model was also established. Microglial activation and IL1R2 levels in retinal tissues were analyzed using immunofluorescence assay. Endothelial cell migration was evaluated by Transwell assay and scratch test, angiogenesis was assessed using ELISA and tube formation assay, and proliferation was evaluated by EdU assay. The HIF1α/PFKFB3 pathway was analyzed by western blot. We observed that IL1R2 expression was predicted to be upregulated in ROP and was increased in hypoxia-treated BV2 cells. Additionally, IL1R2 levels were upregulated in the retinal tissues of OIR mice and correlated with microglial activation. In vitro experiments, we found that hypoxia promoted endothelial cell migration, angiogenesis, proliferation, and activated the HIF1α/PFKFB3 pathway, which were rescued by IL1R2 knockdown. Moreover, NHWD-870 (a HIF1α/PFKFB3 pathway inhibitor) suppressed endothelial cell migration, angiogenesis, and proliferation induced by IL1R2 overexpression. In conclusion, IL1R2 facilitates the migration, angiogenesis, and proliferation of choroidal endothelial cells by activating the HIF1α/PFKFB3 pathway to regulate ROP progression.

100 Deals associated with NHWD-870

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Advanced NUT Carcinoma	Phase 2	CN	Ningbo Wenda Pharmaceutical Technology Co., Ltd	25 Apr 2024
Diffuse Large B-Cell Lymphoma	Phase 2	CN	Ningbo Wenda Pharmaceutical Technology Co., Ltd	26 Oct 2023
Non-Hodgkin Lymphoma	Phase 2	-	Ningbo Wenda Pharmaceutical Technology Co., Ltd	-
NUT midline carcinoma	Phase 2	-	Ningbo Wenda Pharmaceutical Technology Co., Ltd	-
Advanced Malignant Solid Neoplasm	Phase 1	CN	Ningbo Wenda Pharmaceutical Technology Co., Ltd	29 Jan 2021
Melanoma, Cutaneous Malignant	Phase 1	CN	Ningbo Wenda Pharmaceutical Technology Co., Ltd	29 Jan 2021
Mucosal Melanoma	Phase 1	CN	Ningbo Wenda Pharmaceutical Technology Co., Ltd	29 Jan 2021
Non-Small Cell Lung Cancer	Phase 1	CN	Ningbo Wenda Pharmaceutical Technology Co., Ltd	29 Jan 2021
Small Cell Lung Cancer	Phase 1	CN	Ningbo Wenda Pharmaceutical Technology Co., Ltd	29 Jan 2021