预约演示
更新于：2026-09-17
Quemliclustat
更新于：2026-09-17
概要
基本信息
非在研机构- |
最高研发阶段临床3期 |
首次获批日期- |
最高研发阶段(中国)- |
特殊审评孤儿药 (美国)、孤儿药 (欧盟) |
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结构/序列
分子式C20H24ClFN4O9P2 |
InChIKeyMFYLCAMJNGIULC-KCVUFLITSA-N |
CAS号2105904-82-1 |
关联
15
项与 Quemliclustat 相关的临床试验NCT07667335
A Phase Ib/II Study to Evaluate the Safety and Efficacy of Enfortumab Vedotin Plus Pembrolizumab in Combination With Quemliclustat in Unresectable Locally Advanced and Metastatic Urothelial Carcinoma
NCT07364214
A Phase 1, Open-Label Study to Characterize the Metabolism, Excretion, and Mass Balance of a Single Intravenous Dose of 100 mg Containing 75 µCi of [14C]-Quemliclustat in Healthy Adult Male Participants
JPRN-jRCT2051250013
Platform Study of Zipalertinib in Patients with EGFR-mutant NSCLC (REZILIENT5 study)
100 项与 Quemliclustat 相关的临床结果
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100 项与 Quemliclustat 相关的转化医学
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100 项与 Quemliclustat 相关的专利（医药）
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24
项与 Quemliclustat 相关的文献（医药）2026-10-01PHYTOMEDICINE
Celastrol Ameliorates Systemic Lupus Erythematosus via Restoring Nt5e/ adenosine-dependent Th17/Treg Balance
Article
作者: Li, Yiping ; Xu, Danna ; Zheng, Yingying ; Wen, Chengping ; Wang, Chenxi ; Li, Suling ; Pang, Zhengyi ; Huang, Lin ; Zhang, Yun ; Jiang, Zhangsheng ; He, Zhixing
BACKGROUND:
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the breakdown of immune tolerance, systemic inflammation, and multi-organ damage. The imbalance between T helper 17 (Th17) cells and regulatory T (Treg) cells is a key driver in SLE pathogenesis.
PURPOSE:
This study aimed to investigate whether Celastrol (Cel), a natural triterpenoid derived from Tripterygium wilfordii, exerts therapeutic effects in SLE by modulating the Th17/Treg balance, and to explore the underlying molecular mechanism.
STUDY DESIGN:
An in vivo study using the MRL/lpr lupus-prone mouse model was conducted to evaluate therapeutic efficacy, complemented by in vitro assays and molecular analysis to identify target pathways.
METHODS:
MRL/lpr mice were orally administered Cel and disease progression was assessed via survival analysis, spleen pathology, autoantibody levels, and renal histopathology. T cell subsets were analyzed using flow cytometry and Western blot. Proteomic profiling was performed to identify potential molecular targets, followed by molecular docking, molecular dynamics simulations, cellular thermal shift assay (CETSA), MicroScale Thermophoresis (MST) and surface plasmon resonance (SPR) to validate target engagement. AB680, a pharmacological inhibitor of ecto-5'-nucleotidase (Nt5e), was used to confirm the functional role of Nt5e.
RESULTS:
Cel treatment significantly improved survival, reduced splenomegaly, suppressed anti-dsDNA/ANA autoantibody levels, and alleviated renal damage in lupus-prone mice. It promoted Treg cell differentiation and inhibited Th17 polarization, evidenced by increased Foxp3 expression and decreased STAT3 phosphorylation. Nt5e was identified as a direct binding target of Cel. Target engagement was validated through CETSA, MST and SPR, and inhibition of Nt5e by AB680 partially reversed Cel's therapeutic effects, indicating that Nt5e mediates its immunomodulatory action.
CONCLUSION:
Our results indicate that Cel restores the Th17/Treg balance via upregulating Nt5e, thereby ameliorating SLE-associated injury. This study thus provides novel insights into the mechanism of Cel treating SLE and underscores the therapeutic potential of targeting Nt5e in SLE.
2026-04-01NATURE MEDICINE
Quemliclustat and chemotherapy with or without zimberelimab in metastatic pancreatic adenocarcinoma: a randomized phase 1 trial
Article
作者: DiRenzo, Daniel M ; Wang, Ning ; Ulahannan, Susanna V ; Walters, Matthew J ; Wainberg, Zev A ; Manji, Gulam A ; Scott, Jennifer R ; Mrouj, Karim ; Oberstein, Paul E ; Beagle, Brandon ; Kaplan, Angelo ; Pant, Shubham ; Wu, Wilson ; Weeder, Ben ; Spigel, David R ; Cho, Soonweng ; O'Reilly, Eileen M ; Bahary, Nathan ; Shitole, Shravani ; Saeed, Anwaar ; Uboha, Nataliya V ; Kabbarah, Omar ; Ensign, Lisa G ; Kim, Ji Yun
Abstract:
Quemliclustat potently inhibits CD73, a key enzyme producing immunosuppressive adenosine. In a phase 1b trial (ARC-8), we evaluated safety and efficacy of quemliclustat combined with gemcitabine/nab-paclitaxel (G/nP) with or without zimberelimab (anti-programmed cell death protein 1 (PD-1)) in first-line metastatic pancreatic ductal adenocarcinoma (PDAC). During the dose-escalation phase, 22 patients were enrolled across five dose levels of quemliclustat (25 mg, 50 mg, 75 mg, 100 mg or 125 mg) with G/nP + zimberelimab. During the dose-expansion phase, 116 patients were enrolled, beginning with a single-arm, non-randomized cohort receiving quemliclustat 100 mg + G/nP + zimberelimab, followed by a randomized cohort in which patients were assigned in a 2:1 ratio to receive quemliclustat 100 mg + G/nP with or without zimberelimab. The primary endpoint was safety and tolerability; secondary endpoints included assessments of clinical activity and survival. In all treatment arms, the safety profile was consistent with that of G/nP. Clinical response rates and survival outcomes were encouraging.
NR4A
family gene expression was upregulated by adenosine in vitro and by chemotherapy in human PDACs. High tumor
NR4A
expression was associated with improved overall survival (OS) in ARC-8 but not in two external cohorts from the PRINCE (G/nP + nivolumab (nivo)) or Morpheus-PDAC (G/nP) trials. Spatial tissue analyses revealed a scarcity of activated T cells near regions with high
NR4A1
expression, consistent with an immunosuppressed tumor microenvironment. In paired pretreatment/posttreatment biopsies, maximal downregulation of
NR4A
expression was associated with T cell activation and improved OS, pointing to a biological link between tumor adenosine and clinical benefit. ClinicalTrials.gov identifier:
NCT04104672
.
2026-01-09ACS Pharmacology & Translational Science
Potent Competitive Inhibitors of Ecto-5′-nucleotidase (CD73) based on 6-(Het)aryl-7-deazapurine Ribonucleoside 5′-
O
-Bisphosphonates
Article
作者: Konvalinka, Jan ; Poštová Slavětínská, Lenka ; Lepšík, Martin ; Šácha, Pavel ; Hocek, Michal ; Šinkevičiu̅tė, Ugnė ; Blažková, Kristýna ; Řezáč, Jan ; Staník, Radek ; Šímová, Magdalena ; Tichý, Michal ; Ormsby, Tereza
CD73 generates immunosuppressive adenosine in the tumor microenvironment and is a promising target for cancer immunotherapy. We have designed and systematically studied diverse 2-substituted 7-deazapurine ribonucleoside 5'-O-bisphosphonates bearing a variety of (het)-aryl groups at position 6 and discovered their highly potent and selective CD73 inhibition activity. The most active compounds (with single-digit picomolar K i) contained bicyclic (het)-aryl groups at position 6 in combination with chlorine at position 2. Further optimization of pharmacokinetic properties identified inhibitors with low clearance, long half-life, high solubility, and excellent selectivity over CD39 and NTPDase3. They effectively suppressed adenosine formation in MDA-MB-231 cells, rescued CD8+ T cell activation, and were nontoxic to human fibroblasts. Overall, their profile compares favorably with AB680, a CD73 inhibitor currently in phase I/II clinical trials.
103
项与 Quemliclustat 相关的新闻（医药）100 项与 Quemliclustat 相关的药物交易
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外链
| KEGG | Wiki | ATC | Drug Bank |
|---|---|---|---|
| D12373 | - | - | - |
研发状态
10 条进展最快的记录, 后查看更多信息
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| 转移性胰腺导管腺癌 | 临床3期 | 美国 | 2024-12-13 | |
| 转移性胰腺导管腺癌 | 临床3期 | 日本 | 2024-12-13 | |
| 转移性胰腺导管腺癌 | 临床3期 | 澳大利亚 | 2024-12-13 | |
| 转移性胰腺导管腺癌 | 临床3期 | 奥地利 | 2024-12-13 | |
| 转移性胰腺导管腺癌 | 临床3期 | 比利时 | 2024-12-13 | |
| 转移性胰腺导管腺癌 | 临床3期 | 加拿大 | 2024-12-13 | |
| 转移性胰腺导管腺癌 | 临床3期 | 捷克 | 2024-12-13 | |
| 转移性胰腺导管腺癌 | 临床3期 | 法国 | 2024-12-13 | |
| 转移性胰腺导管腺癌 | 临床3期 | 德国 | 2024-12-13 | |
| 转移性胰腺导管腺癌 | 临床3期 | 意大利 | 2024-12-13 |
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临床结果
临床结果
适应症
分期
评价
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临床1期 | 122 | quemliclustat + GnP or quemliclustat + zimberelimab + GnP | 積廠築襯衊範襯淵築鑰(廠衊壓網顧襯衊網蓋廠) = 繭夢鏇構簾齋衊夢積壓 積製憲構鑰積獵夢醖襯 (夢獵壓網餘繭鏇觸鏇顧 ) 更多 | 积极 | 2026-05-29 | ||
GnP | 積廠築襯衊範襯淵築鑰(廠衊壓網顧襯衊網蓋廠) = 壓糧獵選鹹衊鏇糧窪糧 積製憲構鑰積獵夢醖襯 (夢獵壓網餘繭鏇觸鏇顧 ) 更多 | ||||||
临床1期 | 122 | 範窪鬱構範醖範齋衊廠(壓糧廠網鹹衊製糧夢淵) = 遞遞窪鹽鏇觸獵願醖憲 壓願憲網憲鬱衊窪齋網 (觸簾選鬱鹹憲鏇窪壓廠, 24 ~ 61) 更多 | 积极 | 2024-01-18 | |||
範窪鬱構範醖範齋衊廠(壓糧廠網鹹衊製糧夢淵) = 蓋觸壓觸醖淵網餘餘鏇 壓願憲網憲鬱衊窪齋網 (觸簾選鬱鹹憲鏇窪壓廠, 28 ~ 48) 更多 | |||||||
临床1期 | 转移性胰腺腺癌 一线 | 13 | overall | 窪膚膚夢製糧淵鬱鑰觸(餘簾範齋襯繭觸簾範網) = 積願夢顧壓鹹齋廠築網 餘蓋繭壓觸鑰憲範繭壓 (遞觸蓋艱鹽鑰壓獵顧壓 ) 更多 | 积极 | 2021-01-20 | |
(Cohort 1 (25 mg AB680)) | 淵艱糧糧選選構壓廠糧(範廠遞繭醖願廠遞艱鹽) = 窪製觸衊願鏇願餘窪鏇 齋餘製窪糧構齋獵艱築 (壓襯壓壓選夢簾糧蓋觸 ) 更多 | ||||||
临床1期 | 转移性胰腺癌 一线 | 19 | 鹽壓餘衊醖憲壓窪網鏇(築餘憲餘簾獵淵範鹽鏇) = fatigue (68%), anemia (53%), alopecia (42%), diarrhea (42%) and neutrophil count decrease (42%) 積鬱蓋鏇築獵艱膚夢襯 (遞簾繭獵網遞選構窪襯 ) 更多 | 积极 | 2021-01-15 | ||
临床1期 | - | - | 壓餘鹹夢襯鑰網簾廠獵(鹽築鏇醖膚製窪衊構觸) = 遞製蓋範鹹鹽醖齋餘積 繭顧製餘蓋製鏇淵顧鑰 (簾鑰獵鏇願壓餘襯醖鏇 ) | - | 2019-08-06 |
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