Request Demo
Last update 25 Feb 2026
HSK-31858
Last update 25 Feb 2026
Overview
Basic Info
Drug Type Small molecule drug |
Synonyms CHF10196, HSK 31858, HSK-31858 + [1] |
Target |
Action inhibitors |
Mechanism DPP-1 inhibitors(Cathepsin C inhibitors) |
Therapeutic Areas |
Active Indication |
Inactive Indication- |
Originator Organization |
Active Organization |
Inactive Organization- |
License Organization |
Drug Highest PhasePhase 3 |
First Approval Date- |
RegulationBreakthrough Therapy (China) |
Login to view timeline
Structure/Sequence
Molecular FormulaC23H23FN4O4 |
InChIKeyONJDRXNRBKHINH-UWJYYQICSA-N |
CAS Registry2762114-61-2 |
Related
11
Clinical Trials associated with HSK-31858CTR20253262
评价HSK31858片在非囊性纤维化支气管扩张患者中长期安全性的多中心、单臂、开放扩展研究
[Translation] A multicenter, single-arm, open-label extension study to evaluate the medium- and long-term safety of HSK31858 tablets in patients with non-cystic fibrosis bronchiectasis
NCT07134465
A Single-center, Open-label, Two-period, Fixed-sequence Clinical Study to Evaluate the Effect of Itraconazole on the Pharmacokinetics of HSK31858 in Healthy Subjects
NCT06820749
A Multicenter, Randomized, Double-blind, Placebo-controlled Phase II Study to Evaluate the Efficacy and Safety of HSK31858 Tablets in Patients with Airway Mucus Hypersecretion in Chronic Airway Inflammatory Diseases
100 Clinical Results associated with HSK-31858
Login to view more data
100 Translational Medicine associated with HSK-31858
Login to view more data
100 Patents (Medical) associated with HSK-31858
Login to view more data
5
Literatures (Medical) associated with HSK-3185801 Aug 2025BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
Safety, tolerability, pharmacokinetics and pharmacodynamics of HSK31858, a novel oral dipeptidyl peptidase‐1 inhibitor, in healthy volunteers: An integrated phase 1, randomized, double‐blind, placebo‐controlled, single‐ and multiple‐ascending dose study
Article
Author: Jie Hou ; Yuhao Wang ; Chao Yu ; Mengyue Hu ; Meixia Chen ; Hanmo Liu ; Nan Wu ; Lu Wang
Abstract:
Aim:
Dipeptidyl peptidase‐1 (DPP‐1) inhibitors have been studied for the treatment of neutrophil‐mediated inflammatory diseases including bronchiectasis, bronchial asthma and cystic fibrosis. This study evaluated the pharmacokinetics, pharmacodynamics, safety and tolerability of DPP‐1 inhibitor HSK31858 in healthy Chinese volunteers.
Methods:
Volunteers in Part A randomly received single doses of HSK31858 (15, 40, 60 and 80 mg) or placebo in fasted states. The 40‐mg cohort also received HSK31858 40 mg or placebo in fed states. In Part B, volunteers randomly received HSK31858 10, 20 and 40 mg or placebo once daily for 28 days in fasted states. The primary endpoints were safety and tolerability of HSK31858.
Results:
Among 38 volunteers in Part A and 36 in Part B, HSK31858 was well tolerated; no deaths, serious adverse events, or discontinuations due to adverse events occurred. The median Tmax was 0.75 to 1.0 h and the mean terminal t1/2 was 16.5 to 21.0 h in the fasted state with single doses of HSK31858. Both Cmax and AUC0‐t exhibited a dose‐dependent rise. Food had no effect on AUC. Multiple doses of HSK31858 demonstrated a similar pharmacokinetics profile, with about 2‐fold accumulation in AUC. HSK31858 dose‐dependently inhibited neutrophil count‐normalized neutrophil elastase (NEnorm) activity. The maximal percentage decrease in NEnorm activity relative to baseline during 28 days of HSK31858 treatments was 13.6% and 76.4% with HSK31858 10 and 40 mg once‐daily, respectively.
Conclusion:
HSK31858 was safe and well tolerated. The pharmacokinetics and pharmacodynamics profile of HSK31858 supports further clinical development for the treatment of neutrophil‐mediated inflammatory diseases.
Trial Registration:
NCT05663593.
01 Jul 2025Journal of Thoracic Disease
Dipeptidyl peptidase 1 inhibitors and neutrophilic inflammation in bronchiectasis: a narrative review
Review
Author: Tang, Rui-Di ; Guan, Wei-Jie ; Yue, Jun-Qing ; Chalmers, James D
Background and Objective:
Bronchiectasis is a chronic respiratory disease characterized by predominantly neutrophilic inflammation, recurrent infection and pathological dilatation of the airways. Current therapeutic strategies primarily target infections and improving mucus clearance. However, no current treatment can directly ameliorate neutrophilic inflammation. Recently, dipeptidyl peptidase 1 (DPP-1) inhibitors effectively abrogated neutrophilic inflammation in bronchiectasis. This narrative review aimed to analyze the structural characteristics and functional effects of DPP-1, explore the mechanism of DPP-1 inhibitors in bronchiectasis, and highlight major clinical trial findings.
Methods:
We performed an online electronic search for relevant English literature on PubMed and Web of Science databases, with the keywords of "dipeptidyl peptidase 1", "cathepsin C", "cathepsin C structure", "cathepsin C maturation", "cathepsin C loss-of-function", "neutrophil serine proteases and bronchiectasis", "neutrophil serine proteases and cathepsin C", "neutrophil serine proteases and DPP-1", "DPP-1 inhibitors", "cathepsin C inhibitors", "DPP-1 inhibitors and bronchiectasis", "cathepsin C inhibitors and bronchiectasis". Two authors (R.D.T. and J.Q.Y.) independently searched and reviewed the articles.
Key Content and Findings:
Excessive and uncontrolled release of neutrophil serine proteases (NSPs) can lead to airway inflammatory responses and structural damage in bronchiectasis. Elevated levels of neutrophil elastase (NE) and other neutrophil markers in the airway are associated with exacerbations and lung function decline. In light of the pivotal role of DPP-1 in eliciting neutrophilic inflammation, several DPP-1 inhibitors have been developed and entered clinical trials for safety and efficacy assessment in bronchiectasis. Of these, brensocatib markedly prolonged the time to the first exacerbation and decreased the exacerbation frequency via decreasing the activity of NSPs. The phase III ASPEN trial has been completed and confirms reduced exacerbations and slower lung function decline with DPP-1 inhibitor treatment. Treatment with BI 1291583 reduced the risk of bronchiectasis exacerbations in the phase II Airleaf® trial. HSK31858 significantly decreased the exacerbation frequency and prolonged the time to the first exacerbation in the latest phase II trial among the Chinese population.
Conclusions:
DPP-1 inhibitors have exhibited promising effects in improving several major clinical outcomes in bronchiectasis via suppressing the activity of NSPs.
01 May 2025Lancet Respiratory Medicine
Effects of the DPP-1 inhibitor HSK31858 in adults with bronchiectasis in China (SAVE-BE): a phase 2, multicentre, double-blind, randomised, placebo-controlled trial
Article
Author: Xu, Xing-xiang ; Huang, Zeng-yu ; Li, Fang-qiong ; Xie, Shi-guang ; Ye, Huan ; Xie, Shi-Guang ; Lin, Ying-xiang ; Xu, Xing-Xiang ; Wu, Xiao-fei ; Liu, Han-mo ; Zhong, Nan-shan ; Zhang, Xian-ming ; Zhong, Nan-Shan ; Zhang, Xiao-ju ; Lin, Dian-Jie ; Qiu, Rong ; Xiong, Hao ; Chalmers, James D ; Zhang, Xian-Ming ; Zheng, Yao ; Lin, Dian-jie ; Huang, Yan-ming ; Guan, Wei-jie ; Yang, Zhi-Ren ; Li, Fang-Qiong ; Xu, Jin-fu ; Huang, Yan-Ming ; Shen, Yao ; Xiao, Zu-ke ; Xu, Jin-Fu ; Guan, Wei-Jie ; Zhao, Li ; Zhang, Guo-jun ; Song, Yuan-lin ; Li, Yuan-yuan ; Gao, Ling-yun ; Gao, Ling-Yun ; Cao, Jie ; Li, Ya-ming ; Yang, Zhi-ren ; Zhou, Hua ; Wen, Fu-qiang ; Qu, Jie-ming ; Wang, Ling-wei ; Chalmers, James Duncan ; Xiao, Zu-Ke
BACKGROUND:
Airway neutrophil inflammation with excessive neutrophil serine proteases is implicated in frequent exacerbations of bronchiectasis. HSK31858 is a novel reversible inhibitor of DPP-1. We aimed to assess the efficacy and safety of HSK31858 in decreasing the frequency of bronchiectasis exacerbations among adults with bronchiectasis.
METHODS:
SAVE-BE was a phase 2, double-blind, randomised, placebo-controlled trial in 25 tertiary centres in China. Participants were aged 18 years or older with a physician diagnosis of bronchiectasis, according to chest high-resolution CT showing bronchial dilatation and compatible respiratory symptoms, and at least two exacerbations within 12 months before screening. Participants were randomly assigned (1:1:1) via a central interactive web-response system to receive 20 mg HSK31858, 40 mg HSK31858, or placebo, orally, once daily for 24 weeks. Randomisation was stratified by exacerbation frequency in the previous year (less than three vs three or more annually) and study investigators and participants were masked to group assignment for analysis of study outcomes. The primary endpoint was the annualised exacerbation frequency over 24 weeks, assessed in the full analysis set. Safety was monitored throughout the study. This trial is registered with ClinicalTrials.gov, NCT05601778.
FINDINGS:
Between Dec 6, 2022, and March 31, 2024, 292 patients were screened, 226 of whom were enrolled and randomly assigned (75 to the 20 mg HSK31858 group, 76 to the 40 mg HSK31858 group, and 75 to the placebo group. 74 patients received 20 mg HSK31858, 75 received 40 mg HSK31858, and 75 received placebo and were included in the full analysis set. In the full analysis set, 136 (61%) participants were female and 88 (39%) were male. The mean annualised frequency of exacerbations was 1·00 per person-year (SD 1·44) in the 20 mg HSK31858 group, 0·75 per person-year (1·37) in the 40 mg HSK31858 group, and 1·88 per person-year (1·97) in the placebo group. The least-squares mean frequency of exacerbations was 1·05 per person-year (95% CI 0·73-1·51) in the 20 mg HSK31858 group, 0·83 per person-year (0·55-1·25) in the 40 mg HSK31858 group, and 2·01 per person-year (1·53-2·63) in the placebo group. The incidence rate ratio compared with placebo was 0·52 (95% CI 0·34-0·80; p=0·0031) for the 20 mg HSK31858 group and 0·41 (0·26-0·66; p=0·0002) for the 40 mg HSK31858 group. The incidence of adverse events was similar across the three groups. Neither HSK31858 dose was associated with an increased incidence of adverse events of special interest (eg, hyperkeratosis, gingivitis, or life-threatening infections).
INTERPRETATION:
Both HSK31858 doses improved clinical outcomes in adults with bronchiectasis, significantly reducing the exacerbation frequency compared with placebo. The development of new drugs targeted at amelioration of neutrophilic inflammation (eg, via suppression of DPP-1 activity) might lead to new options for hindering the progression of bronchiectasis.
FUNDING:
Haisco.
2
News (Medical) associated with HSK-3185821 Nov 2023
License out/inPhase 2
100 Deals associated with HSK-31858
Login to view more data
R&D Status
10 top R&D records. to view more data
Login
| Indication | Highest Phase | Country/Location | Organization | Date |
|---|---|---|---|---|
| Non-cystic fibrosis bronchiectasis | Phase 3 | China | 26 Sep 2024 | |
| airway disease | Phase 2 | China | 01 Dec 2024 | |
| Catarrhal bronchitis | Phase 2 | China | 01 Dec 2024 | |
| Pulmonary Disease, Chronic Obstructive | Phase 2 | China | 01 Dec 2024 | |
| Asthma | Phase 2 | China | 22 Oct 2024 | |
| Acute Lung Injury | Phase 1 | China | 28 Oct 2024 | |
| Respiratory Distress Syndrome, Acute | Phase 1 | China | 28 Oct 2024 |
Login to view more data
Clinical Result
Clinical Result
Indication
Phase
Evaluation
View All Results
Phase 1 | - | - | lynedpoohl(nnyxzbbdby) = qtbjmhvlgj nlvwcnaquo (nktifjwywq ) View more | - | 01 Aug 2025 | ||
hdvxrwcgvc(khcokqcsqe) = igcofdwayw jzjvzhjjkm (fekaoildfl ) View more | |||||||
Phase 2 | 136 | HSK31858 20 mg | zasxqnhmmd(fjvnqjcgqa) = yaqwwzrgdn hsrsegergb (mperhpyqjr, 1.44) | Positive | 25 Mar 2025 | ||
HSK31858 40 mg | zasxqnhmmd(fjvnqjcgqa) = fkeyktvdvv hsrsegergb (mperhpyqjr, 1.37) | ||||||
NCT05663593 (ERS2023) Manual  | Phase 1 | - | pevhiuymrq(neohfafwqe) = HSK31858 was absorbed rapidly, with no significant accumulation of Cmax, while AUC accumulation was more pronounced. There was dose-dependent inhibitory effect in whole blood NE activity, with maximum inhibition of 13.6%, 44.1%,and 76.4% in the 10mg,20mg, and 40mg groups, repectively. uzueubunsl (hvimvpigam ) | Positive | 09 Sep 2023 |
Login to view more data
Translational Medicine
Boost your research with our translational medicine data.
login
or
Deal
Boost your decision using our deal data.
login
or
Core Patent
Boost your research with our Core Patent data.
login
or
Clinical Trial
Identify the latest clinical trials across global registries.
login
or
Approval
Accelerate your research with the latest regulatory approval information.
login
or
Regulation
Understand key drug designations in just a few clicks with Synapse.
login
or
AI Agents Built for Biopharma Breakthroughs
Accelerate discovery. Empower decisions. Transform outcomes.
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
Sign up for free
Chemical
Chemical Structures Search & Analysis
Sign up for free