Dezapelisib(Dezapelisib) - 药物靶点：PI3Kδ_在研适应症：伯基特淋巴瘤，巨球蛋白血症_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Dezapelisib (USAN)

+ [2]

靶点

PI3Kδ

作用方式

抑制剂

作用机制

PI3Kδ抑制剂(磷脂酰肌醇-3激酶δ抑制剂)

治疗领域

在研适应症

非在研适应症

原研机构

在研机构

非在研机构-

最高研发阶段临床1期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构/序列

分子式C20H16FN7OS

InChIKeyRSIWALKZYXPAGW-NSHDSACASA-N

CAS号1262440-25-4

关联

2

项与 Dezapelisib 相关的临床试验

NCT02456675

/ Terminated临床2期

A Phase 2, Open-Label Study of the Safety and Efficacy of INCB40093 and INCB40093 Combined With Itacitinib (INCB039110) in Subjects With Relapsed or Refractory Hodgkin Lymphoma

A Phase 2, open-label study to evaluate the safety and efficacy of INCB040093 as monotherapy and as combination therapy with itacitinib (INCB039110) in subjects with relapsed or refractory Hodgkin Lymphoma.

开始日期2015-06-01

申办/合作机构

Incyte Corp.

NCT01905813

/ Active, not recruiting临床1期

A Phase 1, Open-label, Dose Escalation, Safety and Tolerability Study of INCB040093 in Subjects With Previously Treated B-Cell Malignancies

The study will be conducted in three parts. Part 1 is a dose escalation phase to determine the maximum tolerated dose (MTD) of INCB040093, a PI3Kδ inhibitor, or a tolerated, pharmacologically active dose; Part 2 will evaluate the combination of INCB040093 and itacitinib (INCB039110), a JAK1 inhibitor, to determine the MTD of the combination or a tolerated dose that produces substantial pharmacologic inhibition of both targets; Part 3 will further evaluate the chosen doses of INCB040093 alone and in combination with itacitinib (INCB039110) in subjects with relapsed/refractory B-cell malignancies.

开始日期2013-06-30

申办/合作机构

Incyte Corp.

100 项与 Dezapelisib 相关的临床结果

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100 项与 Dezapelisib 相关的转化医学

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100 项与 Dezapelisib 相关的专利（医药）

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4

项与 Dezapelisib 相关的文献（医药）

2019-11-14·ACS Medicinal Chemistry Letters3区 · 医学

INCB050465 (Parsaclisib), a Novel Next-Generation Inhibitor of Phosphoinositide 3-Kinase Delta (PI3Kδ)

3区 · 医学

Article

作者: Shin, Niu ; Polam, Padmaja ; Scherle, Peggy ; He, Xin ; Diamond, Sharon ; Yue, Eddy W. ; Sparks, Richard B. ; Falahatpisheh, Nikoo ; Mei, Song ; Hall, Leslie ; Zhu, Wenyu ; Zhang, Ke ; Maduskuie, Thomas ; Glenn, Joseph ; Douty, Brent ; Koblish, Holly K. ; Li, Yanlong ; Wang, Kathy He ; Feldman, Patricia ; He, Chunhong ; Feng, Hao ; Katiyar, Kamna ; Metcalf, Brian ; Combs, Andrew P. ; Yeleswaram, Swamy ; Yao, Wenqing ; Li, Yu ; Covington, Maryanne ; Li, Yun-Long ; Wayland, Brian ; Xue, Chu-Biao

A medicinal chemistry effort focused on identifying a structurally diverse candidate for phosphoinositide 3-kinase delta (PI3Kδ) led to the discovery of clinical candidate INCB050465 (20, parsaclisib). The unique structure of 20 contains a pyrazolopyrimidine hinge-binder in place of a purine motif that is present in other PI3Kδ inhibitors, such as idelalisib (1), duvelisib (2), and INCB040093 (3, dezapelisib). Parsaclisib (20) is a potent and highly selective inhibitor of PI3Kδ with drug-like ADME properties that exhibited an excellent in vivo profile as demonstrated through pharmacokinetic studies in rats, dogs, and monkeys and through pharmacodynamic and efficacy studies in a mouse Pfeiffer xenograft model.

2018-07-19·Blood1区 · 医学

Phase 1 study of the PI3Kδ inhibitor INCB040093 ± JAK1 inhibitor itacitinib in relapsed/refractory B-cell lymphoma

1区 · 医学

Article

作者: Diefenbach, Catherine S. ; Scherle, Peggy ; Phillips, Tycel J. ; Sher, Taimur ; Barr, Paul M. ; Zhou, Li ; Johnston, Patrick ; Talpaz, Moshe ; Chen, Xuejun ; Forero-Torres, Andres ; Pulini, Jennifer

Key PointsINCB040093 was active across lymphoma subtypes, and the addition of itacitinib provided substantial activity in classic Hodgkin lymphoma. INCB040093 ± itacitinib had a manageable safety and tolerability profile; severe hepatic adverse effects were less common with the combination.

2018-01-01·The Journal of Pharmacology and Experimental Therapeutics

INCB040093 Is a Novel PI3Kδ Inhibitor for the Treatment of B Cell Lymphoid Malignancies

Article

作者: Favata, Margaret ; Hollis, Gregory ; Katiyar, Kamna ; Huber, Reid ; Rupar, Mark ; Leffet, Lynn ; Koblish, Holly ; Liu, Mike ; Yeleswaram, Swamy ; Burn, Timothy ; Newton, Robert ; Mei, Song ; Li, Jun ; Vaddi, Kris ; Wang, Kathy He ; Fridman, Jordan ; Shuey, Dana ; Soloviev, Maxim ; Scherle, Peggy ; Li, Yun-Long ; Li, Yanlong ; Yao, Wenqing ; Hall, Leslie ; Diamond, Sharon ; Covington, Maryanne ; Yang, Gengjie ; Combs, Andrew ; Wang, Qian ; Bowman, Kevin ; Shin, Niu ; He, Xin ; Rumberger, Beth

Phosphatidylinositol 3-kinase delta (PI3Kδ) is a critical signaling molecule in B cells and is considered a target for development of therapies against various B cell malignancies. INCB040093 is a novel PI3Kδ small-molecule inhibitor and has demonstrated promising efficacy in patients with Hodgkin's lymphoma in clinical studies. In this study, we disclose the chemical structure and the preclinical activity of the compound. In biochemical assays, INCB040093 potently inhibits the PI3Kδ kinase, with 74- to >900-fold selectivity against other PI3K family members. In vitro and ex vivo studies using primary B cells, cell lines from B cell malignancies, and human whole blood show that INCB040093 inhibits PI3Kδ-mediated functions, including cell signaling and proliferation. INCB040093 has no significant effect on the growth of nonlymphoid cell lines and was less potent in assays that measure human T and natural killer cell proliferation and neutrophil and monocyte functions, suggesting that the impact of INCB040093 on the human immune system will likely be restricted to B cells. INCB040093 inhibits the production of macrophage-inflammatory protein-1β (MIP-1beta) and tumor necrosis factor-β (TNF-beta) from a B cell line, suggesting a potential effect on the tumor microenvironment. In vivo, INCB040093 demonstrates single-agent activity in inhibiting tumor growth and potentiates the antitumor growth effect of the clinically relevant chemotherapeutic agent, bendamustine, in the Pfeiffer cell xenograft model of non-Hodgkin's lymphoma. INCB040093 has a favorable exposure profile in rats and an acceptable safety margin in rats and dogs. Taken together, data presented in this report support the potential utility of orally administered INCB040093 in the treatment of B cell malignancies.

100 项与 Dezapelisib 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D10924	-	-	DB16137

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
伯基特淋巴瘤	临床1期	美国	Incyte Corp.	2013-06-30
巨球蛋白血症	临床1期	美国	Incyte Corp.	2013-06-30
难治性霍奇金淋巴瘤	临床前	-	Incyte Corp.	2015-06-01

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT01905813 (Pubmed \| Circulation \| Blood) 人工标引	临床1期	难治性B细胞淋巴瘤	121	INCB040093	(鹹襯襯淵齋獵鬱構鏇願) = The most common serious adverse events with monotherapy were pneumonia (n = 5) and pyrexia (n = 4), and with combination Pneumocystis jiroveci pneumonia (n = 5), pneumonia (unrelated to P jiroveci; n = 5), and pyrexia (n = 4). 憲鹽顧鹹廠憲衊鹽廠醖 (餘壓憲鑰鏇繭鏇膚顧蓋 )	积极	2018-07-19
				INCB040093+itacitinib
ICML2015	临床1期	B细胞恶性肿瘤	83	INCB040093 monotherapy	鬱夢醖範鏇簾鑰憲鑰網(遞齋蓋鹽網膚鬱齋廠鬱) = 28% 鬱築齋顧襯簾遞獵簾醖 (選襯淵繭簾淵選糧範鏇 ) 更多	积极	2015-06-09
				INCB040093+INCB039110 combination therapy
NCT01905813 (ASCO2015)	临床1期	复发性经典霍奇金淋巴瘤	17	INCB040093	(鏇觸憲範顧憲憲選簾鏇) = 41% 顧網獵衊製構築夢壓窪 (壓簾願夢鬱積遞網窪網 ) 更多	-	2015-05-20
				INCB040093 + INCB039110