Delving into the Latest Updates on Efatutazone hydrochloride with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Efatutazone, Inolitazone

+ [2]

Target

PPARγ

Mechanism

PPARγ agonists(Peroxisome proliferator-activated receptor γ agonists)

Therapeutic Areas

NeoplasmsEndocrinology and Metabolic DiseaseOther Diseases

Active Indication

Myxoid LiposarcomaAnaplastic Thyroid CarcinomaThyroid cancer recurrent

Inactive Indication

Advanced cancerAdvanced Lung Non-Small Cell CarcinomaColorectal Cancer+ [4]

Originator Organization

Daiichi Sankyo Co., Ltd.

Active Organization

Daiichi Sankyo, Inc.

Inactive Organization

Daiichi Sankyo Co., Ltd.

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC27H29ClN4O5S

InChIKeyJYVSNMNBGHMWQB-UHFFFAOYSA-N

CAS Registry1048002-36-3

View All Structures (2)

This phase II trial studies how well efatutazone dihydrochloride works in treating patients with previously treated myxoid liposarcoma that cannot be removed by surgery. Drugs used in chemotherapy, such as efatutazone dihydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Start Date01 Oct 2014

Sponsor / Collaborator

Alliance Foundation Trials LLC

[+2]

NCT02152137 / CompletedPhase 2IIT

A Phase 2 Study of Efatutazone, an Oral PPAR Agonist, In Combination With Paclitaxel in Patients With Advanced Anaplastic Thyroid Cancer

This phase II trial studies how well inolitazone dihydrochloride (efatutazone dihydrochloride) and paclitaxel work in treating patients with anaplastic thyroid cancer that has spread to other places in the body and usually cannot be cured or controlled with treatment (advanced). Drugs used in chemotherapy, such as efatutazone dihydrochloride and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Start Date01 Sep 2014

Sponsor / Collaborator

Alliance Foundation Trials LLC

[+2]

NCT01504490 / TerminatedPhase 1IIT

A Phase I Study of a Combination of the Proteosome Proliferator-Activated Receptor Gamma Agonist, CS-7017 and the Retinoid X Receptor Agonist, Bexarotene

This study is for patients with advanced solid tumors. The purpose of this study is to test the safety and effectiveness of a new combination of drugs, CS-7017 and Bexarotene in patients with advanced cancer. CS-7017 and Bexarotene both have many effects on cancer cells, including stopping cancer cells from growing and dividing, and causing the cancer cells to die. CS-7017 and Bexarotene work on cancer cells in a similar manner and both drugs together may have an even greater effect against cancer cells, hopefully, increasing the killing of cancer cells.
CS-7017 is an investigational or experimental anti-cancer agent that has not yet been approved by the Food and Drug Administration (FDA) for use in any type of cancer. Bexarotene is an anti-cancer agent that has been approved by the FDA for patients with a specific type of cancer, cutaneous T-cell lymphoma.
This study will help find out what effects the combination of drugs, CS-7017 and Bexarotene, has on cancer. This research is being done because it is not known if CS-7017 is safe to be given with Bexarotene.

Start Date01 Dec 2011

Sponsor / Collaborator

Georgetown University

[+1]

100 Clinical Results associated with Efatutazone hydrochloride

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100 Translational Medicine associated with Efatutazone hydrochloride

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100 Patents (Medical) associated with Efatutazone hydrochloride

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22

Literatures (Medical) associated with Efatutazone hydrochloride

13 Aug 2023·Journal of Biomolecular Structure and Dynamics

In-silico discovery of inhibitors against human papillomavirus E1 protein

Article

Author: Hwang, Siaw San ; Rahman, Taufiq ; Wezen, Xavier Chee ; Gunasinghe, Juliyan ; Yam, Wai Keat

High-risk (HR) Human papillomavirus (e.g. HPV16 and HPV18) causes approximately two-thirds of all cervical cancers in women. Although the first and second-generation vaccines confer some protection against individuals, there are no approved drugs to treat HR-HPV infections to-date. The HPV E1 protein is an attractive drug target because the protein is highly conserved across all HPV types and is crucial for the regulation of viral DNA replication. Hence, we used the Random Forest algorithm to construct a Quantitative-Structure Activity Relationship (QSAR) model to predict the potential inhibitors against the HPV E1 protein. Our QSAR classification model achieved an accuracy of 87.5%, area under the receiver operating characteristic curve of 1.00, and F-measure of 0.87 when evaluated using an external test set. We conducted a drug repurposing campaign by deploying the model to screen the Drugbank database. The top three compounds, namely Cinalukast, Lobeglitazone, and Efatutazone were analyzed for their cell membrane permeability, toxicity, and carcinogenicity. Finally, these three compounds were subjected to molecular docking and 200 ns-long Molecular Dynamics (MD) simulations. The predicted binding free energies for the candidates were calculated using the MM-GBSA method. The binding free energies for Cinalukast, Lobeglitazone, and Efatutazone were -37.84 kcal/mol, -25.30 kcal/mol, and -29.89 kcal/mol respectively. Therefore, we propose their chemical scaffolds for future rational design of E1 inhibitors.Communicated by Ramaswamy H. Sarma.

15 Aug 2021·Cancer ResearchQ1 · MEDICINE

An AIB1 Isoform Alters Enhancer Access and Enables Progression of Early-Stage Triple-Negative Breast Cancer

Q1 · MEDICINE

Article

Author: Riegel, Anna T. ; Loudig, Olivier ; Pearson, Gray W. ; Kushner, Max H. ; Kietzman, William B. ; Graham, Garrett T. ; Schmidt, Marcel O. ; Wellstein, Anton ; Sengupta, Surojeet ; Sharif, Ghada M. ; Campbell, Moray J. ; Nasir, Apsra ; Fineberg, Susan

AbstractAIB1Δ4 is an N-terminally truncated isoform of the oncogene amplified in breast cancer 1 (AIB1) with increased expression in high-grade human ductal carcinoma in situ (DCIS). However, the role of AIB1Δ4 in DCIS malignant progression has not been defined. Here we CRISPR-engineered RNA splice junctions to produce normal and early-stage DCIS breast epithelial cells that expressed only AIB1Δ4. These cells showed enhanced motility and invasion in 3D cell culture. In zebrafish, AIB1Δ4-expressing cells enabled invasion of parental cells when present in a mixed population. In mouse xenografts, a subpopulation of AIB1Δ4 cells mixed with parental cells enhanced tumor growth, recurrence, and lung metastasis. AIB1Δ4 chromatin immunoprecipitation sequencing revealed enhanced binding to regions including peroxisome proliferator-activated receptor (PPAR) and glucocorticoid receptor (GR) genomic recognition sites. H3K27ac and H3K4me1 genomic engagement patterns revealed selective activation of breast cancer-specific enhancer sites by AIB1Δ4. AIB1Δ4 cells displayed upregulated inflammatory response genes and downregulated PPAR signaling gene expression patterns. In the presence of AIB1Δ4 enabler cells, parental cells increased NF-κB and WNT signaling. Cellular cross-talk was inhibited by the PPARγ agonist efatutazone but was enhanced by treatment with the GR agonist dexamethasone. In conclusion, expression of the AIB1Δ4-selective cistrome in a small subpopulation of cells triggers an “enabler” phenotype hallmarked by an invasive transcriptional program and collective malignant progression in a heterogeneous tumor population.Significance:A minor subset of early-stage breast cancer cells expressing AIB1Δ4 enables bulk tumor cells to become invasive, suggesting that selective eradication of this population could impair breast cancer metastasis.

01 Dec 2020·Thyroid Research

Recent advances in the management of anaplastic thyroid cancer

Review

Author: Fugazzola, Laura ; De Leo, Simone ; Trevisan, Matteo

AbstractAnaplastic thyroid cancer (ATC) is undoubtedly the thyroid cancer histotype with the poorest prognosis. The conventional treatment includes surgery, radiotherapy, and conventional chemotherapy. Surgery should be as complete as possible, securing the airway and ensuring access for nutritional support; the current standard of care of radiotherapy is the intensity-modulated radiation therapy; chemotherapy includes the use of doxorubicin or taxanes (paclitaxel or docetaxel) generally with platin (cisplatin or carboplatin). However, frequently, these treatments are not sufficient and a systemic treatment with kinase inhibitors is necessary. These include multitarget tyrosine kinase inhibitors (Lenvatinib, Sorafenib, Sunitinib, Vandetanib, Axitinib, Pazopanib, Pyrazolo-pyrimidine compounds), single target tyrosine kinase inhibitors (Dabrafenib plus Trametinib and Vemurafenib against BRAF, Gefitinib against EGFR, PPARγ ligands (e.g. Efatutazone), Everolimus against mTOR, vascular disruptors (e.g. Fosbretabulin), and immunotherapy (e.g. Spartalizumab and Pembrolizumab, which are anti PD-1/PD-L1 molecules). Therapy should be tailored to the patients and to the tumor genetic profile. A BRAF mutation analysis is mandatory, but a wider evaluation of tumor mutational status (e.g. by next-generation sequencing) is desirable. When a BRAFV600E mutation is detected, treatment with Dabrafenib and Trametinib should be preferred: this combination has been approved by the Food and Drug Administration for the treatment of patients with locally advanced or metastatic ATC with BRAFV600E mutation and with no satisfactory locoregional treatment options. Alternatively, Lenvatinib, regardless of mutational status, reported good results and was approved in Japan for treating unresectable tumors. Other single target mutation agents with fair results are Everolimus when a mutation involving the PI3K/mTOR pathway is detected, Imatinib in case of PDGF-receptors overexpression, and Spartalizumab in case of PD-L1 positive tumors. Several trials are currently evaluating the possible beneficial role of a combinatorial therapy in ATC. Since in this tumor several genetic alterations are usually found, the aim is to inhibit or disrupt several pathways: these combination strategies use therapy targeting angiogenesis, survival, proliferation, and may act against both MAPK and PI3K pathways. Investigating new treatment options is eagerly awaited since, to date, even the molecules with the best radiological results have not been able to provide a durable disease control.

100 Deals associated with Efatutazone hydrochloride

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB11894

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Colorectal Cancer	Discovery	DE	Daiichi Sankyo, Inc.	31 Jul 2009
Colorectal Cancer	Discovery	RU	Daiichi Sankyo, Inc.	31 Jul 2009
Colorectal Cancer	Discovery	FR	Daiichi Sankyo, Inc.	31 Jul 2009
Colorectal Cancer	Discovery	PL	Daiichi Sankyo, Inc.	31 Jul 2009
Colorectal Cancer	Discovery	CZ	Daiichi Sankyo, Inc.	31 Jul 2009
Colorectal Cancer	Discovery	IT	Daiichi Sankyo, Inc.	31 Jul 2009
metastatic non-small cell lung cancer	Discovery	IN	Daiichi Sankyo Co., Ltd.	01 Dec 2008
metastatic non-small cell lung cancer	Discovery	RO	Daiichi Sankyo Co., Ltd.	01 Dec 2008
metastatic non-small cell lung cancer	Discovery	PL	Daiichi Sankyo Co., Ltd.	01 Dec 2008
metastatic non-small cell lung cancer	Discovery	US	Daiichi Sankyo Co., Ltd.	01 Dec 2008

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00986440 (CTgov)	Phase 2	Colorectal Cancer	84	Placebo	mddydkvcjy(kobbvkhwix) = pjcpcztbpj opyrwicowb (zmzfsenfjk, bpfxkuqzwg - jqesdspxqu) View more	-	05 Nov 2020
NCT00408434 (CTgov)	Phase 1	Neoplasm Metastasis	32	CS-7017 (CS-7017 0.10 mg)	wcmbvggqhk(ddxbcsyyxh) = heisftktbj vbwifhyynt (hzoooagrkb, cknnwncstb - kwruydjikv) View more	-	19 Oct 2020
				CS-7017 (CS-7017 0.15 mg)	wcmbvggqhk(ddxbcsyyxh) = avylqjrveg vbwifhyynt (hzoooagrkb, defngpgior - wzivpcrgfo) View more
NCT00603941 (CTgov)	Phase 1/2	Anaplastic Thyroid Carcinoma	19	Paclitaxel+CS-7017 (Cohort 1; 0.15 mg CS-7017)	muofeuuslo(dxjepcdlro) = rrrtnnraue vivszplbxk (juunssrcnl, sesutcamcn - ucendlyycm) View more	-	16 Sep 2020
				Paclitaxel+CS-7017 (Cohort 2; 0.30 mg CS-7017)	muofeuuslo(dxjepcdlro) = hszhpbddsy vivszplbxk (juunssrcnl, tvyyqgegvr - hnsyzgyejd) View more
NCT00881569 (CTgov)	Phase 1	Advanced cancer	2	CS-7017 (CS-7017 0.50 mg BID)	(ihzcxvhcnh) = akejvaejmi tfgmhtljiu (rbtiafglnw, adesnudxzg - tdkvegpsgq) View more	-	14 Aug 2020
				CS-7017 (CS-7017 0.75 mg BID)	(ihzcxvhcnh) = gwlgpdikvc tfgmhtljiu (rbtiafglnw, mkasbkcvdp - heqftskhsr) View more
NCT01199068 (CTgov)	Phase 1	Non-Small Cell Lung Cancer	15	CS-7017 (CS-7017 0.25 mg BID; Initial Portion)	vlvnhxwwkh(djdawmkidj) = vgnmsykzms geangnntkg (mhruflopmk, pxzuhztykt - fzsljbkdlz) View more	-	31 Jul 2020
				CS-7017 (CS-7017 0.50 mg BID; Initial Portion)	vlvnhxwwkh(djdawmkidj) = kyjcaojejz geangnntkg (mhruflopmk, ykecfntwhu - psddgedjne) View more
NCT01199055 (CTgov)	Phase 1	Non-Small Cell Lung Cancer	16	CS-7017 (CS-7017 0.25 mg BID; Initial Portion)	muxxnkahqq(cvfdzmcqjo) = bbyvhntmsb owswzylswe (ivghcfwyyt, isocpsqzns - wjeohmzdja) View more	-	07 Jul 2020
				CS-7017 (CS-7017 0.50 mg BID; Initial Portion)	muxxnkahqq(cvfdzmcqjo) = snjdfzqahv owswzylswe (ivghcfwyyt, hlmuzzcuxv - huqhlythwh) View more
NCT01101334 (CTgov)	Phase 2	Advanced Lung Non-Small Cell Carcinoma	90	Erlotinib+CS-7017 (CS-7017 Plus Erlotinib)	cpuqalwlea(qkoaniwvqm) = phbnhxjqkv imqbixmqyy (vwswrxuymz, lmchynvkbf - uqghsnsetz) View more	-	16 Jun 2020
				Erlotinib (Erlotinib)	cpuqalwlea(qkoaniwvqm) = efruspzyxn imqbixmqyy (vwswrxuymz, vyntavmsbo - jawpzrhpad) View more
NCT00806286 (CTgov)	Phase 2	metastatic non-small cell lung cancer	111	Carboplatin+Paclitaxel+CS7017 (CS7017+Carboplatin+Paclitaxel)	mrdqjevrih(auxbleqmjl) = beweymzzqr daxelvfvbs (tnmddkdiju, fcornginiu - qgmtatlhqz) View more	-	13 May 2020
				Placebo+Carboplatin+Paclitaxel+CS7017 (CS7017-matching Placebo+Carboplatin+Paclitaxel)	mrdqjevrih(auxbleqmjl) = iaeifdsuie daxelvfvbs (tnmddkdiju, ulmfcchqek - jwavmrimlr) View more
NCT02152137 (CTgov)	Phase 2	Anaplastic Thyroid Carcinoma \| Thyroid cancer recurrent	19	paclitaxel+efatutazone	owmnrclsrf(wigswwuvlk) = xiyythpvqk obphcazegg (mfmtnfqttr, ljrndrtlky - rvqsuuhpgo) View more	-	27 Dec 2019
NCT02249949 (CTgov)	Phase 2	Myxoid Liposarcoma	15	efatutazone	qaqvdgskqe(pvixaagfnz) = xvosrbagcy bnvgrgrajc (fkwnlnizzn, fsyvgbbmhr - otbwvkmiwf) View more	-	27 Jun 2019