Delving into the Latest Updates on Atamestane with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

BIOMED 777, BIOMED-777, SH 489

+ [3]

Target

aromatase

Action

inhibitors

Mechanism

aromatase inhibitors(Aromatase inhibitors)

Therapeutic Areas

NeoplasmsSkin and Musculoskeletal DiseasesUrogenital Diseases

Active Indication-

Inactive Indication

Advanced breast cancerBreast CancerMetastatic breast cancer+ [1]

Originator Organization

Bayer AG

Active Organization-

Inactive Organization

Intarcia Therapeutics, Inc.Bayer Schering Pharma AG

License Organization-

Drug Highest PhaseDiscontinuedPhase 3

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC20H26O2

InChIKeyPEPMWUSGRKINHX-TXTPUJOMSA-N

CAS Registry96301-34-7

Protocol 777-CLP-32 is the treatment and survival continuation protocol of Biomed 777-CLP-29, and will continue to compare combined hormonal therapy using the experimental aromatase inhibitor (AI) atamestane combined with the FDA-approved anti-estrogen toremifene (Fareston®), to the single agent FDA-approved aromatase inhibitor letrozole (Femara®) for the treatment of advanced breast cancer. The purpose of this study is to determine whether maximal estrogen suppression achieved via the combination of atamestane, plus toremifene (Fareston®), is more effective than letrozole (Femara®) in delaying the growth of breast cancer.

Start Date01 Nov 2005

Sponsor / Collaborator

Intarcia Therapeutics, Inc.

NCT00097344

/ TerminatedPhase 3

Phase 3 Study of Atamestane Plus Toremifene Versus Letrozole in Advanced Breast Cancer

The purpose of this study is to determine whether maximal estrogen suppression achieved via the combination of an experimental drug, atamestane, plus an FDA-approved drug, toremifene (Fareston®), is more effective than another approved drug, letrozole (Femara®), in delaying the growth of breast cancer, and whether the side effects of the combined hormonal therapy are different from the side effects of letrozole.

Start Date01 Dec 2004

Sponsor / Collaborator

Intarcia Therapeutics, Inc.

NCT00044291

/ CompletedPhase 3

Phase III Study of Atamestane Plus Toremifene Versus Letrozole in Advanced Breast Cancer

The purpose of this study is to determine whether the first line combination hormonal therapy of an experimental drug, atamestane, plus an FDA-approved drug, toremifene (Fareston®), is more effective than another approved drug, letrozole (Femara®), in delaying the growth of breast cancer in postmenopausal patients with locally advanced or metastatic breast cancer, and whether the side effects of the combination are different from the side effects of letrozole.

Start Date01 Jun 2002

Sponsor / Collaborator

Intarcia Therapeutics, Inc.

100 Clinical Results associated with Atamestane

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100 Translational Medicine associated with Atamestane

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100 Patents (Medical) associated with Atamestane

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48

Literatures (Medical) associated with Atamestane

01 Jul 2020·Journal of advanced researchQ2 · CROSS-FIELD

Whole-cell fungal-mediated structural transformation of anabolic drug metenolone acetate into potent anti-inflammatory metabolites

Q2 · CROSS-FIELD

ArticleOA

Author: Siddiqui, Mahwish ; Wang, Wei ; Atta-Ur-Rahman ; Atia-Tul-Wahab ; Wang, Yan ; Jabeen, Almas ; Choudhary, M Iqbal

Seven new derivatives, 6α-hydroxy-1-methyl-3-oxo-5α-androst-1-en-17-yl acetate (2), 6α,17β-dihydroxy-1-methyl-3-oxo-5α-androst-1-en (3), 7β-hydroxy-1-methyl-3-oxo-5α-androst-1-en-17-yl acetate (4), 15β,20-dihydroxy-1-methyl-3-oxo-5α-androst-1-en-17-yl acetate (5), 15β-hydroxy-1-methyl-3-oxo-5α-androst-1-en-17-yl acetate (6), 12β,17β-dihydroxy-1-methyl-3-oxoandrosta-1,4-dien (11), and 7β,15β,17β-trihydroxy-1-methyl-3-oxo-5α-androst-1-en (14), along with six known metabolites, 17β-hydroxy-1-methyl-3-oxoandrosta-1,4-dien (7), 17β-hydroxy-1-methyl-3-oxo-5α-androst-1-en (8), 17β-hydroxy-1-methyl-3-oxo-5β-androst-1-en (9), 1-methyl-5β-androst-1-en-3,17-dione (10), 1-methyl-3-oxoandrosta-1,4-dien-3,17-dione (12), and 17β-hydroxy-1α-methyl-5α-androstan-3-one (13) of metenolone acetate (1), were synthesized through whole-cell biocatalysis with Rhizopus stolonifer, Aspergillus alliaceous, Fusarium lini, and Cunninghamella elegans. Atamestane (12), an aromatase inhibitor, was synthesized for the first time via F. lini-mediated transformation of 1 as the major product. Hydroxylation, dehydrogenation, and reduction were occurred during biocatalysis. Study indicated that F. lini was able to catalyze dehydrogenation reactions selectively. Structures of compounds 1-14 were determined through NMR, HRFAB-MS, and IR spectroscopic data. Compounds 1-14 were identified as non-cytotoxic against BJ human fibroblast cell line (ATCC CRL-2522). Metabolite 5 (81.0 ± 2.5%) showed a potent activity against TNF-α production, as compared to the substrate 1 (62.5 ± 4.4%). Metabolites 2 (73.4 ± 0.6%), 8 (69.7 ± 1.4%), 10 (73.2 ± 0.3%), 11 (60.1 ± 3.3%), and 12 (71.0 ± 7.2%), also showed a good inhibition of TNF-α production. Compounds 3 (IC₅₀ = 4.4 ± 0.01 µg/mL), and 5 (IC₅₀ = 10.2 ± 0.01 µg/mL) showed a significant activity against T-cell proliferation. Identification of selective inhibitors of TNF-α production, and T-cell proliferation is a step forward towards the development of anti-inflammatory drugs.

01 Oct 2019·The Lancet. OncologyQ1 · MEDICINE

Endocrine treatment versus chemotherapy in postmenopausal women with hormone receptor-positive, HER2-negative, metastatic breast cancer: a systematic review and network meta-analysis

Q1 · MEDICINE

Review

Author: Rognoni, Carla ; Arpino, Grazia ; Prat, Aleix ; Milani, Manuela ; De Placido, Sabino ; Giordano, Antonio ; Del Mastro, Lucia ; Thomas, Guglielmo ; Generali, Daniele ; Venturini, Sergio ; Cristofanilli, Massimo ; Giuliano, Mario ; Puglisi, Fabio ; De Placido, Pietro ; Schettini, Francesco ; De Laurentiis, Michelino ; Pistilli, Barbara ; Jerusalem, Guy ; Bachelot, Thomas

BACKGROUND:

Although international guidelines support the administration of hormone therapies with or without targeted therapies in postmenopausal women with hormone-receptor-positive, HER2-negative metastatic breast cancer, upfront use of chemotherapy remains common even in the absence of visceral crisis. Because first-line or second-line treatments, or both, based on chemotherapy and on hormone therapy have been scarcely investigated in head-to-head randomised controlled trials, we aimed to compare these two different approaches.

METHODS:

We did a systematic review and network meta-analysis with a systematic literature search on PubMed, Embase, Cochrane Central Register of Clinical Trials, Web of Science, and online archives of the most relevant international oncology conferences. We included all phase 2 and 3 randomised controlled trials investigating chemotherapy with or without targeted therapies and hormone therapies with or without targeted therapies as first-line or second-line treatments, or both, in postmenopausal women with hormone-receptor-positive, HER2-negative metastatic breast cancer, published between Jan 1, 2000, and Dec 31, 2017. Additional recently published randomised controlled trials relevant to the topic were also subsequently added. No language restrictions were adopted for our search. A Bayesian network meta-analysis was done to compare hazard ratios (HRs) for progression-free survival (the primary outcome), and to compare odds ratios (ORs) for the proportion of patients achieving an overall response (the secondary outcome). All treatments were compared to anastrozole and to palbociclib plus letrozole. This study is registered in the Open Science Framework online public database, registration DOI 10.17605/OSF.IO/496VR.

FINDINGS:

We identified 2689 published results and 140 studies (comprising 50 029 patients) were included in the analysis. Palbociclib plus letrozole (HR 0·42; 95% credible interval [CrI] 0·25-0·70), ribociclib plus letrozole (0·43; 0·24-0·77), abemaciclib plus anastrozole or letrozole (0·42; 0·23-0·76), palbociclib plus fulvestrant (0·37; 0·23-0·59), ribociclib plus fulvestrant (0·48; 0·31-0·74), abemaciclib plus fulvestrant (0·44; 0·28-0·70), everolimus plus exemestane (0·42; 0·28-0·67), and, in patients with a PIK3CA mutation, alpelisib plus fulvestrant (0·39; 0·22-0·66), and several chemotherapy-based regimens, including anthracycline and taxane-containing regimens, were associated with better progression-free survival than was anastrozole alone. No chemotherapy or hormone therapy regimen was significantly better than palbociclib plus letrozole for progression-free survival. Paclitaxel plus bevacizumab was the only clinically relevant regimen that was significantly better than palbociclib plus letrozole in terms of the proportion of patients achieving an overall response (OR 8·95; 95% CrI 1·03-76·92).

INTERPRETATION:

In the first-line or second-line setting, CDK4/6 inhibitors plus hormone therapies are better than standard hormone therapies in terms of progression-free survival. Moreover, no chemotherapy regimen with or without targeted therapy is significantly better than CDK4/6 inhibitors plus hormone therapies in terms of progression-free survival. Our data support treatment guideline recommendations involving the new combinations of hormone therapies plus targeted therapies as first-line or second-line treatments, or in both settings, in women with hormone-receptor-positive, HER2-negative metastatic breast cancer.

FUNDING:

None.

03 Apr 2015·Drug and chemical toxicologyQ4 · MEDICINE

Evidence for the contribution of non-covalent steroid interactions between DNA and topoisomerase in the genotoxicity of steroids

Q4 · MEDICINE

Article

Author: John O. Trent ; Ronald D. Snyder ; Patrick A. Holt ; Jon M. Maguire

Fifty two steroids and 9 Vitamin D analogs were docked into ten crystallographically-defined DNA dinucleotide sites and two human topoisomerase II ATP binding sites using two computational programs, Autodock and Surflex. It is shown that both steroids and Vitamin D analogs exhibit a propensity for non-covalent intercalative binding to DNA. A higher predicted binding affinity was found, however, for steroids and the ATP binding site of topoisomerase; in fact these drugs exhibited among the highest topo II binding observed in over 1370 docked drugs. These findings along with genotoxicity data from 26 additional steroids not subjected to docking analysis, support a mechanism wherein the long known, but poorly understood, clastogenicity of steroids may be attributable to inhibition of topoisomerase. A "proof of principle" experiment with dexamethasone demonstrated this to be the likely mechanism of clastogenicity of, at least, this steroid. The generality of this proposed mechanism of genotoxicity across the steroids and vitamin-D analogs is discussed.

100 Deals associated with Atamestane

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External Link

KEGG	Wiki	ATC	Drug Bank
-	Atamestane	-	DB12194

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Advanced breast cancer	Phase 3	United States	Intarcia Therapeutics, Inc.	01 Jun 2002
Advanced breast cancer	Phase 3	Canada	Intarcia Therapeutics, Inc.	01 Jun 2002
Advanced breast cancer	Phase 3	Russia	Intarcia Therapeutics, Inc.	01 Jun 2002
Advanced breast cancer	Phase 3	Ukraine	Intarcia Therapeutics, Inc.	01 Jun 2002
Metastatic breast cancer	Phase 3	United States	Intarcia Therapeutics, Inc.	01 Oct 2000
Breast Cancer	Phase 2	Germany	Bayer Schering Pharma AG	01 Jan 1999
Prostatic Hyperplasia	Phase 2	Europe	Bayer Schering Pharma AG	01 Nov 1996

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ASCO2006	Phase 3	Advanced breast cancer First line	865	Atamestane 500 mg per day + Toremifene 60 mg per day	eevkemddvr(ztjretwxip) = kqmexuoiez npddaoqcoq (vxuannvhtz )	-	20 Jun 2006
				Letrozole 2.5 mg per day	eevkemddvr(ztjretwxip) = smrootyypv npddaoqcoq (vxuannvhtz )