更新于：2024-05-08
Uproleselan
更新于：2024-05-08
概要
基本信息
药物类型 化学药 |
别名 Uproleselan (USAN/INN)、Uproleselan injection、Uproleselan sodium + [2] |
靶点 |
作用机制 E-sel抑制剂(选择素-E抑制剂) |
在研适应症 |
非在研适应症 |
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)临床3期 |
特殊审评突破性疗法 (美国)、快速通道 (美国)、突破性疗法 (中国) |
结构
分子式C60H109N3NaO27 |
InChIKeyHHTBXHJWLLMOLI-CVDXTIKBSA-N |
CAS号1914993-95-5 |
关联
19
项与 Uproleselan 相关的临床试验A Phase 1 and Pharmacokinetic Study of Uproleselan (GMI-1271, NSC #801708) in Combination With Fludarabine and Cytarabine for Patients With Acute Myeloid Leukemia Myelodysplastic Syndrome or Mixed Phenotype Acute Leukemia That Expresses E-Selectin Ligand on the Cell Membrane and is in Second or Greater Relapse or That is Refractory to Relapse Therapy
A Phase 1/2 Trial of Uproleselan Combined With High Dose Busulfan Pre-Transplant Conditioning in Hematopoietic Stem Cell Transplantation for Patients With Chemotherapy Resistant Acute Myeloid Leukemia
A Pilot Study to Assess the Safety, Tolerability and Efficacy of Selectin Inhibitor Uproleselan (GMI-1271) in Patients With COVID-19 Pneumonia
100 项与 Uproleselan 相关的临床结果
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100 项与 Uproleselan 相关的转化医学
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100 项与 Uproleselan 相关的专利（医药）
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14
项与 Uproleselan 相关的文献（医药）2022-03-01Xenotransplantation3区 · 医学
Effects of human TFPI and CD47 expression and selectin and integrin inhibition during GalTKO.hCD46 pig lung perfusion with human blood
3区 · 医学
Article
作者: Ayares, David ; Karavi, Kasinath ; Phelps, Carol ; Azimzadeh, Agnes ; Connolly, Margaret ; Burdorf, Lars ; Sorrells, Lori ; Pierson, Richard N. ; Habibabady, Zahra A. ; Eyestone, Will ; Pollok, Franziska ; Miura, Shuhei ; Dandro, Amy ; Pratts, Shannon
Abstract:
Background:
Loss of barrier function when GalTKO.hCD46 porcine lungs are perfused with human blood is associated with coagulation pathway dysregulation, innate immune system activation, and rapid sequestration of human formed blood elements. Here, we evaluate whether genetic expression of human tissue factor pathway inhibitor (hTFPI) and human CD47 (hCD47), alone or with combined selectin and integrin adhesion pathway inhibitors, delays GalTKO.hCD46 porcine lung injury or modulates neutrophil and platelet sequestration.
Methods:
In a well‐established paired ex vivo lung perfusion model, GalTKO.hCD46.hTFPI.hCD47 transgenic porcine lungs (hTFPI.hCD47, n = 7) were compared to GalTKO.hCD46 lungs (reference, n = 5). All lung donor pigs were treated with a thromboxane synthase inhibitor, anti‐histamine, and anti‐GPIb integrin‐blocking Fab, and were pre‐treated with Desmopressin. In both genotypes, one lung of each pair was additionally treated with PSGL‐1 and GMI‐1271 (P‐ and E‐selectin) and IB4 (CD11b/18 integrin) adhesion inhibitors (n = 6 hTFPI.hCD47, n = 3 reference).
Results:
All except for two reference lungs did not fail within 480 min when experiments were electively terminated. Selectin and integrin adhesion inhibitors moderately attenuated initial pulmonary vascular resistance (PVR) elevation in hTFPI.hCD47 lungs. Neutrophil sequestration was significantly delayed during the early time points following reperfusion and terminal platelet activation was attenuated in association with lungs expressing hTFPI.hCD47, but additional adhesion pathway inhibitors did not show further effects with either lung genotype.
Conclusion:
Expression of hTFPI.hCD47 on porcine lung may be useful as part of an integrated strategy to prevent neutrophil adhesion and platelet activation that are associated with xenograft injury. Additionally, targeting canonical selectin and integrin adhesion pathways reduced PVR elevation associated with hTFPI.hCD47 expression, but did not significantly attenuate neutrophil or platelet sequestration. We conclude that other adhesive mechanisms mediate the residual sequestration of human formed blood elements to pig endothelium that occurs even in the context of the multiple genetic modifications and drug treatments tested here.
2022-02-24Blood
A nonstick marrow may help to fry leukemia
Communications
作者: Maiti, Abhishek ; Daver, Naval G.
Resistance to cytotoxic therapy and the persistence of leukemia stem cells (LSCs) that drive relapse have been formidable challenges in the field of AML.Non-immunol. leukemia-microenvironmental interactions have been demonstrated to support leukemia cells escape from cytotoxic chemotherapy.In this study authors report the promising results of targeting the bone marrow vascular niche with the endothelial selectin (E-selectin) inhibitor uproleselan in combination with intensive chemotherapy in a phase 1/2 single-arm trial in acute myeloid leukemia (AML).They noted no additive toxicity and encouraging response rates in both the relapsed/refractory (R/R) and first-line settings.
2022-02-24Blood1区 · 医学
Phase 1/2 study of uproleselan added to chemotherapy in patients with relapsed or refractory acute myeloid leukemia
1区 · 医学
Article
作者: Magnani, John L. ; Liesveld, Jane L. ; Thackray, Helen M. ; Bixby, Dale L. ; Marlton, Paula ; Feldman, Eric J. ; DeAngelo, Daniel J. ; Becker, Pamela S. ; Jonas, Brian A. ; O’Dwyer, Michael E. ; Advani, Anjali S.
Abstract:
Uproleselan (GMI-1271) is a novel E-selectin antagonist that disrupts cell survival pathways, enhances chemotherapy response, improves survival in mouse xenograft and syngeneic models, and decreases chemotherapy toxicity in vivo. A phase 1/2 study evaluated the safety, tolerability, and antileukemic activity of uproleselan (5-20 mg/kg) with MEC (mitoxantrone, etoposide, and cytarabine) among patients with relapsed/refractory (R/R) acute myeloid leukemia (AML). Among the first 19 patients, no dose-limiting toxicities were observed. The recommended phase 2 dose (RP2D) was 10 mg/kg twice daily. An additional 47 patients with R/R AML were treated with uproleselan at the RP2D plus MEC. At the RP2D, the remission rate (complete response [CR]/CR with incomplete count recovery [CRi]) was 41% (CR, 35%), and the median overall survival (OS) was 8.8 months. In a separate cohort, 25 newly diagnosed patients age ≥60 years received uproleselan at the RP2D plus cytarabine and idarubicin (7 + 3). In these frontline patients, the CR/CRi rate was 72% (CR, 52%), and the median OS was 12.6 months. The addition of uproleselan was associated with low rates of oral mucositis. E-selectin ligand expression on leukemic blasts was higher in patients with relapsed vs primary refractory AML and in newly diagnosed older patients with high-risk cytogenetics and secondary AML. In the R/R cohort, E-selectin expression >10% was associated with a higher response rate and improved survival. The addition of uproleselan to chemotherapy was well tolerated, with high remission rates, low induction mortality, and low rates of mucositis, providing a strong rationale for phase 3 randomized confirmatory studies. This trial was registered at www.clinicaltrials.gov as #NCT02306291.
44
项与 Uproleselan 相关的新闻（医药）2024-05-08
临床3期临床结果临床失败
2024-05-06
·医药魔方
临床3期临床成功
2024-05-06
临床3期抗体药物偶联物临床2期上市批准临床失败
100 项与 Uproleselan 相关的药物交易
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研发状态
| 适应症 | 最高研发状态 | 国家/地区 | 公司 |
|---|---|---|---|
| 复发性急性髓细胞白血病 | 临床3期 | 英国 更多 | |
| 成人急性髓性白血病 | 临床3期 | 中国 更多 | |
| 多发性骨髓瘤 | 临床2期 | 美国 更多 | |
| 实体瘤 | 无进展 | 美国 更多 | |
| 干细胞动员 | 无进展 | 美国 更多 |
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临床结果
临床结果
适应症
分期
评价
查看全部结果
临床2期 | 51 | (Uproleselan + Standard of Care Melphalan) | 築膚製製憲積窪簾醖選(廠獵齋齋憲醖網憲餘鏇) = 襯範齋餘壓鹹蓋憲製窪 夢淵網願積壓觸齋製範 (鬱鑰鏇膚窪積衊憲襯顧, 蓋廠繭顧觸鹹鬱觸積獵 ~ 築範鹹鹽鏇齋遞繭製夢) 更多 | - | 2023-12-15 | ||
Placebo+Melphalan (Placebo + Standard of Care Melphalan) | 築膚製製憲積窪簾醖選(廠獵齋齋憲醖網憲餘鏇) = 鏇廠觸窪願夢窪觸鬱襯 夢淵網願積壓觸齋製範 (鬱鑰鏇膚窪積衊憲襯顧, 鹽鑰顧鏇構齋範膚構鹽 ~ 膚繭糧糧壓醖範淵鑰網) 更多 | ||||||
临床1/2期 | 20 | 獵廠選襯夢醖網觸壓顧(蓋鹹願憲膚蓋構鏇構網) = 獵範襯餘網醖襯夢遞繭 齋鹽淵淵餘蓋艱鑰醖繭 (壓蓋遞衊窪壓壓遞繭觸 ) 更多 | - | 2023-12-10 | |||
临床1/2期 | 6 | 構鏇醖鏇襯鑰醖網衊獵(範廠餘鏇齋鏇簾夢憲艱) = 廠淵淵膚遞壓顧願積窪 餘獵憲構衊選醖餘顧衊 (顧築鏇獵獵膚繭憲壓築, 鏇艱糧鏇構構壓鹹觸獵 ~ 遞積廠鑰鑰淵繭鹹廠簾) 更多 | - | 2023-07-10 | |||
临床1期 | 急性髓性白血病 一线 | 8 | 鏇網蓋範衊網顧鏇範壓(蓋壓製獵製夢選鑰鏇衊) = 繭膚積壓遞鏇鏇鑰齋築 餘窪觸糧選衊衊觸鬱獵 (衊積網夢衊範鬱構積簾 ) 更多 | 积极 | 2022-11-15 | ||
临床1/2期 | 10 | 鹽範製衊齋簾淵餘遞遞(築餘淵淵衊鏇壓遞糧鬱) = The most common SAEs were ≥ grade 3 neutropenic fever (70%), (including 2 grade 5 events), grade 3 bleeding (10%), and grade 2 thrombosis (5%) 糧願範壓淵鬱襯選願製 (糧衊願範積鹽觸衊繭襯 ) | 积极 | 2022-11-15 | |||
临床1/2期 | - | Chemotherapy+Uproleselan | 艱餘範範遞鏇構繭觸鏇(觸餘簾憲積憲築餘淵獵) = 10 mg/kg twice daily 淵壓網餘鬱醖膚憲築糧 (構簾糧觸窪構選範積製 ) | 积极 | 2021-09-20 | ||
临床2期 | 24 | 積網積選簾簾鹹製網鹹(糧窪蓋壓膚鑰夢鑰鬱築) = 獵艱積築壓衊選艱膚鬱 憲網壓餘壓鏇網醖醖餘 (蓋網網構齋窪窪製廠醖 ) | - | 2017-05-30 | |||
临床1/2期 | 47 | 獵鹽糧選積窪衊鏇鬱膚(淵積鏇簾鏇願遞廠顧鏇) = 13% 憲網廠遞獵觸鹽鑰夢簾 (糧憲獵蓋醖醖醖淵壓獵 ) 更多 | 积极 | 2017-05-18 | |||
临床2期 | 24 | 構願鏇顧獵艱範鏇繭遞(膚獵餘襯齋顧糧鏇簾醖) = 47% 願簾鏇觸夢鑰範壓遞鏇 (蓋鏇鏇鏇膚鑰願鏇獵顧 ) 更多 | 积极 | 2017-05-18 |
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