Delving into the Latest Updates on Amcasertib with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Amcasertib (USAN/INN)

+ [3]

Target

NANOG

Action

modulators

Mechanism

NANOG modulators(Nanog homeobox modulators)

Therapeutic Areas

NeoplasmsDigestive System DisordersEndocrinology and Metabolic Disease+ [3]

Active Indication-

Inactive Indication

Advanced cancerAdvanced Hepatocellular CarcinomaAdvanced Malignant Solid Neoplasm+ [7]

Originator Organization

Avania LLC

Active Organization-

Inactive Organization

Sumitomo Pharma America, Inc.

Avania LLC

1Globe Biomedical Co Ltd

+ [1]

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC31H33N5O2S

InChIKeyQDWKGEFGLQMDAM-UHFFFAOYSA-N

CAS Registry1129403-56-0

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.

Start Date13 Mar 2017

Sponsor / Collaborator

Sumitomo Pharma America, Inc.

NCT02232646

/ WithdrawnPhase 2

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.

Start Date01 Jan 2017

Sponsor / Collaborator

Sumitomo Pharma America, Inc.

NCT02483247

/ CompletedPhase 1

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.

Start Date01 Sep 2015

Sponsor / Collaborator

Sumitomo Pharma America, Inc.

100 Clinical Results associated with Amcasertib

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100 Translational Medicine associated with Amcasertib

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100 Patents (Medical) associated with Amcasertib

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6

Literatures (Medical) associated with Amcasertib

01 Jan 2025·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

Author: 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.

21 Jun 2021·Chemical Research in ToxicologyQ3 · MEDICINE

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

Q3 · MEDICINE

Article

Author: 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.

01 Jun 2020·Gynecologic OncologyQ2 · MEDICINE

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

Q2 · MEDICINE

Article

Author: 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 Deals associated with Amcasertib

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External Link

KEGG	Wiki	ATC	Drug Bank
D10903	-	-	DB14866

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hepatobiliary cancer	Phase 2	Canada	Sumitomo Pharma America, Inc.	01 Feb 2015
Advanced Hepatocellular Carcinoma	Phase 2	United States	Sumitomo Pharma America, Inc.	01 Dec 2014
Bile Duct Neoplasms	Phase 2	-	Avania LLC	-
Bile Duct Neoplasms	Phase 2	-	Avania LLC	-
Bile Duct Neoplasms	Phase 2	-	1Globe Biomedical Co Ltd	-
Bile Duct Neoplasms	Phase 2	-	1Globe Biomedical Co Ltd	-
Hepatocellular Carcinoma	Phase 2	-	1Globe Biomedical Co Ltd	-
Hepatocellular Carcinoma	Phase 2	-	1Globe Biomedical Co Ltd	-
Hepatocellular Carcinoma	Phase 2	-	Avania LLC	-
Hepatocellular Carcinoma	Phase 2	-	Avania LLC	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02432690 (CTgov)	Phase 2	Recurrent ovarian cancer	13	BBI503	rameqfregz(pvmiujvxfu) = jckfjcqgiu dtawywxfze (mbldpxhjgh, ehqtizlwjs - ykdxuernnm) View more	-	29 Aug 2022
NCT01781455 (ASCO2017)	Phase 1/2	Adenoid Cystic Carcinoma	14	Amcasertib	(hcgckphnyj) = xylihuyfdz zxnmlvkeqd (svceungzkk ) View more	-	30 May 2017
NCT01781455 (ASCO2017)	Phase 1/2	Advanced Head and Neck Carcinoma	21	Amcasertib	(zmfcjqsxgm) = gsnbihdwfz icdmarhxli (sgloxhmubq ) View more	-	30 May 2017
NCT01781455 (ASCO2016)	Phase 1	Advanced Head and Neck Carcinoma	33	BB503	(jhyftqjdcn) = Grade 3 AE included rapidly reversible diarrhea (n = 5) and nausea/vomiting (n = 1) cliyixkhll (ahjqsabndo )	Positive	20 May 2016
NCT01781455 (ASCO2015)	Phase 1	Advanced Colorectal Adenocarcinoma	47	BBI503 monotherapy	(iihqehqnuc) = eiytlzdgli utzffawiue (ofiomvlywk )	-	20 May 2015
NCT01781455 (ASCO2014)	Phase 1	HR-positive/HER2-low Solid Tumors	26	BBI503	(oprlouompg) = nxqlkasgeo osnkusbcmv (gifdafyzpm ) View more	-	20 May 2014