Amcasertib(Amcasertib) - 药物靶点：NANOG_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Amcasertib (USAN/INN)

+ [3]

靶点

NANOG

作用方式

调节剂

作用机制

NANOG调节剂(Nanog homeobox modulators)

治疗领域

肿瘤消化系统疾病内分泌与代谢疾病+ [3]

在研适应症-

非在研适应症

晚期癌症晚期肝细胞癌晚期恶性实体瘤+ [7]

原研机构

Avania LLC

在研机构-

非在研机构

Sumitomo Pharma America, Inc.

Avania LLC

北京强新生物科技有限公司

+ [1]

最高研发阶段终止临床2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C31H33N5O2S

InChIKeyQDWKGEFGLQMDAM-UHFFFAOYSA-N

CAS号1129403-56-0

关联

9

项与 Amcasertib 相关的临床试验

NCT02232620

/ Terminated临床2期

A Phase II Clinical Study of BBI503 in Adult Patients With Advanced Gastrointestinal Stromal Tumors

This is an open label, multi-center, phase II study of BBI503 administered to adult patients with advanced gastrointestinal stromal tumor who have exhausted all currently approved standard anti-cancer treatment options. BBI503 will be administered orally, daily, in continuous 28-day cycles at a dose of 300 mg once daily. Cycles will be repeated until patients are no longer clinically benefiting from therapy due to disease progression, adverse events, or another discontinuation criterion.
Safety, tolerability and efficacy of BBI503 will be assessed for the duration of study treatment.

开始日期2017-03-13

申办/合作机构

Sumitomo Pharma America, Inc.

NCT02232646

/ Withdrawn临床2期

A Phase II Clinical Study of BBI503 in Adult Patients With Advanced Urologic Malignancies

This is an open label, multi-center, Phase II study of BBI503 administered to adult patients with selected advanced urologic malignancies. The primary objective of this study is to evaluate the disease control rate of patients with renal cell cancer and urothelial carcinoma treated with BBI503.

开始日期2017-01-01

申办/合作机构

Sumitomo Pharma America, Inc.

NCT02483247

/ Completed临床1期

A Phase Ib/II Clinical Study of BBI503 in Combination With Selected Anti-Cancer Therapeutics in Adult Patients With Advanced Cancer

This is an open label, multi-center, Phase 1/2 study of BBI503 administered in combination with selected anti-cancer therapeutics in adult patients with advanced cancer. The goal of the study is to determine the safety, tolerability, and RP2D of BBI503 in combination with each of the selected anti-cancer agents.

开始日期2015-09-01

申办/合作机构

Sumitomo Pharma America, Inc.

100 项与 Amcasertib 相关的临床结果

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100 项与 Amcasertib 相关的转化医学

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100 项与 Amcasertib 相关的专利（医药）

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6

项与 Amcasertib 相关的文献（医药）

2025-01-01·Naunyn-Schmiedeberg's Archives of Pharmacology

In silico method and bioactivity evaluation to discover novel antimicrobial agents targeting FtsZ protein: Machine learning, virtual screening and antibacterial mechanism study

Article

作者: Qin, Qi ; Ruan, Wei ; Lan, Feixiang ; Zheng, Pengwu ; Zhao, Jing ; Xie, Zhouling ; Tu, Yuanbiao ; Wang, Linxiao ; Zhu, Wufu

This research paper utilizes a fused-in-silico approach alongside bioactivity evaluation to identify active FtsZ inhibitors for drug discovery. Initially, ROC-guided machine learning was employed to obtain almost 13182 compounds from three libraries. After conducting virtual screening to assess the affinity of 2621 acquired compounds, cluster analysis and bonding model analysis led to the discovery of five hit compounds. Additionally, antibacterial activity assays and time-killing kinetics revealed that T3995 could eliminate Staphylococcus aureus ATCC6538 and Bacillus subtilis ATCC9732, with MIC values of 32 and 2 μg/mL. Further morphology and FtsZ polymerization assays indicated that T3995 could be an antimicrobial inhibitor by targeting FtsZ protein. Moreover, hemolytic toxicity evaluation demonstrated that T3995 is safe at or below 16 ug/mL concentration. Additionally, bonding model analysis explained how the compound T3995 can display antimicrobial activity by targeting the FtsZ protein. In conclusion, this study presents a promising FtsZ inhibitor that was discovered through a fused computer method and bioactivity evaluation.

2021-06-21·Chemical Research in Toxicology3区 · 医学

Reactive Metabolites from Thiazole-Containing Drugs: Quantum Chemical Insights into Biotransformation and Toxicity

3区 · 医学

Article

作者: Khatun, Samima ; Bharatam, Prasad V. ; Jaladanki, Chaitanya K. ; Gohlke, Holger

Drugs containing thiazole and aminothiazole groups are known to generate reactive metabolites (RMs) catalyzed by cytochrome P450s (CYPs). These RMs can covalently modify essential cellular macromolecules and lead to toxicity and induce idiosyncratic adverse drug reactions. Molecular docking and quantum chemical hybrid DFT study were carried out to explore the molecular mechanisms involved in the biotransformation of thiazole (TZ) and aminothiazole (ATZ) groups leading to RM epoxide, S-oxide, N-oxide, and oxaziridine. The energy barrier required for the epoxidation is 13.63 kcal/mol, that is lower than that of S-oxidation, N-oxidation, and oxaziridine formation (14.56, 17.90, and 20.20, kcal/mol respectively). The presence of the amino group in ATZ further facilitates all the metabolic pathways, for example, the barrier for the epoxidation reaction is reduced by ∼2.5 kcal/mol. Some of the RMs/their isomers are highly electrophilic and tend to form covalent bonds with nucleophilic amino acids, finally leading to the formation of metabolic intermediate complexes (MICs). The energy profiles of these competitive pathways have also been explored.

2020-06-01·Gynecologic Oncology2区 · 医学

Short-term organoid culture for drug sensitivity testing of high-grade serous carcinoma

2区 · 医学

Article

作者: Tepper, Clifford G ; Karnezis, Anthony N ; Leiserowitz, Gary S ; Smith, Lloyd H ; De Souza, Cristabelle ; Chen, Hui ; Gotimer, Kristin ; Chien, Jeremy

OBJECTIVECancer patient-derived organoids (PDOs) grow as three dimensional (3D) structures in the presence of extracellular matrix and have been found to represent the original tumor's genetic complexity. In addition, PDOs can be grown and subjected to drug sensitivity testing in a shorter time course and with lesser expense than patient-derived xenograft models. Many patients with recurrent ovarian cancer develop malignant effusions that become refractory to chemotherapy. Since these same patients often present for palliative aspiration of ascites or pleural effusions, there is a potential opportunity to obtain tumor specimens in the form of multicellular spheroids (MCS) present in malignant effusion fluids. Our objective was to develop a short duration culture of MCS from ovarian cancer malignant effusions in conditions selected to support organoid growth and use them as a platform for empirical drug sensitivity testing.METHODSIn this study, malignant effusion specimens were collected from patients with high-grade serous ovarian carcinoma (HGSOC). MCS were recovered and subjected to culture conditions designed to support organoid growth. In a subset of specimens, RNA-sequencing was performed at two time points during the short-term culture to determine changes in transcriptome in response to culture conditions. Organoid induction was also characterized in these specimens using Ki67 staining and histologic analysis. Drug sensitivity testing was performed on all specimens.RESULTSOur model describes organoids formed within days of primary culture, which can recapitulate the histological features of malignant ascites fluid and can be expanded for at least 6 days. RNA-seq analysis of four patient specimens showed that within 6 days of culture, there was significant up-regulation of genes related to cellular proliferation, epithelial-mesenchymal transition, and KRAS signaling pathways. Drug sensitivity testing identified several agents with therapeutic potential.CONCLUSIONSShort duration organoid culture of MCS from HGSOC malignant effusions can be used as a platform for empiric drug sensitivity testing. These ex vivo models may be helpful in screening new or existing therapeutic agents prior to individualized treatment options.

100 项与 Amcasertib 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D10903	-	-	DB14866

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
肝胆癌	临床2期	加拿大	Sumitomo Pharma America, Inc.	2015-02-01
晚期肝细胞癌	临床2期	美国	Sumitomo Pharma America, Inc.	2014-12-01
胆管癌	临床2期	-	Avania LLC	-
胆管癌	临床2期	-	Avania LLC	-
胆管癌	临床2期	-	北京强新生物科技有限公司	-
胆管癌	临床2期	-	北京强新生物科技有限公司	-
肝细胞癌	临床2期	-	北京强新生物科技有限公司	-
肝细胞癌	临床2期	-	北京强新生物科技有限公司	-
肝细胞癌	临床2期	-	Avania LLC	-
肝细胞癌	临床2期	-	Avania LLC	-

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临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT02432690 (CTgov)	临床2期	复发性卵巢癌	13	BBI503	廠齋膚鹽製觸齋鑰簾壓(糧簾夢醖築襯遞繭膚構) = 窪製選簾膚鹹廠壓構廠選築齋鏇鑰壓鏇製遞襯 (壓壓襯膚鏇淵網鏇衊構, 鹽製齋網襯獵鹽夢簾糧 ~ 膚廠鏇夢選窪鹹醖蓋鏇) 更多	-	2022-08-29
NCT01781455 (ASCO2017)	临床1/2期	腺样囊性癌	14	Amcasertib	(顧夢網醖構餘範鹹獵鹽) = 選獵齋窪築製襯蓋壓製獵廠鏇鹹積鹽衊衊窪膚 (膚鹹蓋積鹹鹹簾淵衊壓 ) 更多	-	2017-05-30
NCT01781455 (ASCO2017)	临床1/2期	晚期头颈癌	21	Amcasertib	(遞遞製簾網鑰憲觸鹽醖) = 膚糧壓衊憲齋遞鑰醖壓鑰構憲鹽齋製鏇獵簾鬱 (簾觸醖醖廠艱廠膚觸窪 ) 更多	-	2017-05-30
NCT01781455 (ASCO2016)	临床1期	晚期头颈癌	33	BB503	(鏇鹽蓋鬱淵壓繭鏇齋選) = Grade 3 AE included rapidly reversible diarrhea (n = 5) and nausea/vomiting (n = 1) 淵淵鹽構製糧願製顧壓 (範淵鹽膚遞築鏇鏇鹽選 )	积极	2016-05-20
NCT01781455 (ASCO2015)	临床1期	晚期结直肠腺癌	47	BBI503 monotherapy	(膚遞網顧築窪網構積構) = 憲積獵夢積夢觸簾鹹構製齋夢製窪餘範觸壓鑰 (齋窪繭簾積餘範鬱淵齋 )	-	2015-05-20
NCT01781455 (ASCO2014)	临床1期	HR阳性/HER2低表达实体瘤	26	BBI503	(淵繭鑰鬱鹹鑰構憲積窪) = 遞鹽積範膚遞壓夢網壓膚壓膚顧衊願築選鹹選 (鹽鹽餘構網製範網遞窪 ) 更多	-	2014-05-20