A Multicenter, Randomized, Double-Blind, Placebo-Controlled, 2-Period, 2-Arm, 4-Sequence, Crossover Phase 1b Study to Assess the Safety, Tolerability, and Pharmacokinetics of Ang-3070 in Subjects With Idiopathic Pulmonary Fibrosis Who Are Treatment-Naïve or Who Have Failed or Refused Standard of Care Treatment

The purpose of this study is to assess safety and tolerability of once daily (QD) and twice daily (BID) dosing of ANG-3070 in subjects with idiopathic pulmonary fibrosis (IPF) who are treatment-naïve, refused therapy, or discontinued for any reason current standard of care with nintedanib or pirfenidone.

Start Date01 Jun 2022

Sponsor / Collaborator

Angion Biomedica Corp.

CTR20213113

/ RecruitingPhase 1

一项评价ICP-033在实体瘤患者中的安全性、耐受性、药代动力学的I 期临床试验

[Translation] A Phase I clinical trial evaluating the safety, tolerability, and pharmacokinetics of ICP-033 in patients with solid tumors

主要目的：评价不同剂量的ICP-033治疗晚期实体瘤的安全性和耐受性。次要目的：初步评估ICP-033治疗晚期实体瘤的药代动力学（PK）特征;初步探索ICP-033治疗实体瘤的有效性。

[Translation]

Primary objective: To evaluate the safety and tolerability of different doses of ICP-033 in the treatment of advanced solid tumors. Secondary objective: To preliminarily evaluate the pharmacokinetic (PK) characteristics of ICP-033 in the treatment of advanced solid tumors; to preliminarily explore the effectiveness of ICP-033 in the treatment of solid tumors.

Start Date09 Mar 2022

Sponsor / Collaborator

Beijing InnoCare Pharma Tech Co., Ltd.

NCT05367232

/ RecruitingPhase 1

A Phase I Clinical Trial to Evaluate the Safety, Tolerability, and Pharmacokinetics of ICP-033 in Patients With Solid Tumors

A Dose finding Study to Evaluate the Safety, Tolerability and Pharmacokinetics and Preliminary Anti-Tumor Activity of ICP-033 Tablets in Patients with Advanced Solid Tumors.

Start Date25 Feb 2022

Sponsor / Collaborator

Beijing InnoCare Pharma Tech Co., Ltd.

100 Clinical Results associated with DDR1 x DDR2

100 Translational Medicine associated with DDR1 x DDR2

0 Patents (Medical) associated with DDR1 x DDR2

128

Literatures (Medical) associated with DDR1 x DDR2

01 Nov 2024·British Journal of Pharmacology

A highly selective inhibitor of discoidin domain receptor‐1 (DDR1‐IN‐1) protects corneal epithelial cells from YAP/ACSL4‐mediated ferroptosis in dry eye

Article

Author: Li, Yue ; Dai, Yiqin ; Xu, Jianjiang ; Zhang, Jing

Background and PurposeThis study investigated the involvement of discoidin domain receptor (DDR) in dry eye and assessed the potential of specific DDR inhibitors as a therapeutic strategy for dry eye by exploring the underlying mechanism.Experimental ApproachDry eye was induced in Wistar rats by applying 0.2% benzalkonium chloride (BAC), after which rats were treated topically for 7 days with DDR1‐IN‐1, a selective inhibitor of DDR1. Clinical manifestations of dry eye were assessed on Day‐7 post‐treatment. Histological evaluation of corneal damage was performed using haematoxylin and eosin (H&E) staining. In vitro, immortalized human corneal epithelial cells (HCECs) exposed to hyperosmotic stress (HS) were treated with varying doses of DDR1‐IN‐1 for 24 h. The levels of lipid peroxidation in dry eye corneas or HS‐stimulated HCECs were assessed. Protein levels of DDR1/DDR2 and related pathways were detected by western blotting. The cellular distribution of acyl‐CoA synthetase long chain family member 4 (ACSL4) and Yes‐associated protein (YAP) was evaluated using immunohistochemistry or immunofluorescent staining.Key ResultsIn dry eye corneas, only DDR1 expression was significantly up‐regulated compared with normal controls. DDR1‐IN‐1 treatment significantly alleviated dry eye symptoms in vivo. The treatment remarkably reduced lipid hydroperoxide (LPO) levels and suppressed the expression of ferroptosis markers, particularly ACSL4. Overexpression or reactivation of YAP diminished the protective effects of DDR1‐IN‐1, indicating the involvement of the Hippo/YAP pathway in DDR1‐targeted therapeutic effects.Conclusions and ImplicationsThis study confirms the significance of DDR1 in dry eye and highlights the potential of selective DDR1 inhibitor(s) for dry eye treatment.

13 Jul 2024·Biological and Pharmaceutical Bulletin

Expression of the Discoidin Domain Receptor Family Depended on Glucose and Their High Expression in Arterial Tissues in the Rat Model of Type 2 Diabetes

Article

Author: Nguyen, Quynh-Mai ; Yang, Beom-Seok ; Phan, Trong-Nhat

The active form of discoidin domain receptors (DDRs) is expressed in cell surface and regulated post-translationally by glucose. The DDR2 and DDR1 transfected in HEK293 cells were expressed mainly in their active forms with sizes of 130 and 120 kDa, respectively. DDRs were observed predominantly as 100 kDa proteins in glucose-depleted culture conditions. However, transfection of endothelial growth factor receptor (EGFR) in HEK293 cells resulted in the expression of only one form regardless of glucose concentration. Vascular smooth muscle cells, HT1080s, and MDA-MB-231 cancer cells expressed DDRs in their active forms in high glucose concentrations, which did not occur with EGFR. In diabetic rats, DDRs were expressed at high levels in arterial tissue but EGFR was not highly expressed. Taken together, these results suggest that DDRs expression depends on glucose concentration it may cooperate in the development of atherosclerosis and kidney fibroblasts, promoting nephropathy in diabetic rats.

01 Jan 2024·The Journal of General and Applied Microbiology

Addition of α-1,3-glucan-binding domains to α-1,3-glucanase Agn1p from　 <i>Schizosaccharomyces pombe</i> enhances hydrolytic activity of insoluble α-1,3-glucan

Article

Author: Makabe, Koki ; Takahashi, Masaki ; Yokomichi, Moe ; Horaguchi, Yui ; Konno, Hiroyuki ; Xu, Fusheng ; Yano, Shigekazu

The glycoside hydrolase (GH) 71 α-1,3-glucanase (Agn1p) from Schizosaccharomyces pombe consists of an N-terminal signal sequence and a catalytic domain. Meanwhile, the GH87 α-1,3-glucanase (Agl-KA) from Bacillus circulans KA-304 consists of an N-terminal signal sequence, a first discoidin domain (DS1), a carbohydrate-binding module family 6 (CBM6), a threonine and proline repeat linker (TP), a second discoidin domain (DS2), an uncharacterized domain, and a catalytic domain. DS1, CBM6, and DS2 exhibit α-1,3-glucan binding activity. This study involved genetically fusing TP, DS1, CBM6, TP, and DS2 to the C-terminus of Agn1p, generating the fusion enzyme Agn1p-DCD. The fusion enzyme was then expressed in Escherichia coli and purified from the cell-free extract. Agn1p-DCD and Agn1p exhibited similar characteristics, such as optimal pH, optimal temperature, pH stability, and thermostability. Insoluble α-1,3-glucan (1%) hydrolyzing assay showed that Agn1p-DCD and Agn1p released approximately 7.6 and 5.0 mM of reducing sugars, respectively, after 48 h of reaction. Kinetic analysis and an α-1,3-glucan binding assay indicated that the addition of DS1, CBM6, and DS2 enhanced the affinity of Agn1p for α-1,3-glucan. Moreover, Agn1p-DCD contributed to enhancing the fungal growth inhibition activity when combined with a mixture of GH19 chitinase and GH16 β-1,3-glucanase.

Analysis

Perform a panoramic analysis of this field.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis