Delving into the Latest Updates on Marimastat with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Marimastat (USAN/INN), BB 2516, BB-2516

+ [2]

Target

MMPs

Mechanism

MMPs inhibitors(Matrix metalloproteinase inhibitors)

Therapeutic Areas

NeoplasmsNervous System DiseasesDigestive System Disorders+ [4]

Active Indication-

Inactive Indication

Breast CancerGliomaHead and Neck Neoplasms+ [8]

Originator Organization

Merck & Co., Inc.

Active Organization-

Inactive Organization

Mitsubishi Tanabe Pharma Corp.

Merck Sharp & Dohme Corp.ILEX Oncology Services, Inc.

Drug Highest PhaseDiscontinuedPhase 3

First Approval Date-

Regulation-

Structure

Molecular FormulaC15H29N3O5

InChIKeyOCSMOTCMPXTDND-OUAUKWLOSA-N

CAS Registry154039-60-8

3 patients were enrolled in each of 3 study cohorts. There three cohorts were given differing, incrementally larger doses of this phase I drug. The same safety measures are being obtained on all patients. Efficacy measures were individualized as enrolllees do not have the same underlying vascular anomaly. The study is structured to include a 24 month drug-phase and a 24 month follow-up phase. The study is now closed to enrollment.

Start Date01 Oct 2000

Sponsor / Collaborator

The Children's Hospital Corp.

NCT00003010 / CompletedPhase 3IIT

A Randomized Phase III Trial of Marimastat Versus Placebo in Patients With Metastatic Breast Cancer Who Have Responding or Stable Disease After Induction Chemotherapy

RATIONALE: Marimastat may stop the growth of breast cancer by stopping blood flow to the tumor. It is not known whether chemotherapy is more effective with or without marimastat for breast cancer.
PURPOSE: Randomized double-blinded phase III trial to compare the effectiveness of marimastat with that of no further therapy in treating women who have metastatic breast cancer that is responding or stable after chemotherapy.

Start Date02 Dec 1997

Sponsor / Collaborator

Eastern Cooperative Oncology Group

[+2]

NCT00003011 / CompletedPhase 3

A Phase III Study of Marimastat in Patients With Small Cell Lung Cancer Following a Response to First Line Chemotherapy

RATIONALE: Marimastat may stop the growth of lung cancer by stopping blood flow to the tumor. It is not yet known if marimastat is an effective treatment for small cell lung cancer.
PURPOSE: Randomized phase III trial to compare the effectiveness of marimastat with a placebo following chemotherapy in treating patients who have small cell lung cancer.

Start Date31 Jan 1997

Sponsor / Collaborator

NCIC Clinical Trials Group

100 Clinical Results associated with Marimastat

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100 Translational Medicine associated with Marimastat

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100 Patents (Medical) associated with Marimastat

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267

Literatures (Medical) associated with Marimastat

25 Oct 2023·Aging

Chronic kidney disease causes blood-brain barrier breakdown via urea-activated matrix metalloproteinase-2 and insolubility of tau protein.

Article

Author: Susa, Koichiro ; Ida, Saaya ; Uchida, Shinichi ; Koide, Takaaki ; Takahashi, Naohiro ; Yanagi, Tomoki ; Mori, Yutaro ; Matsuki, Hisazumi ; Fujiki, Tamami ; Mandai, Shintaro ; Shiwaku, Hiroki ; Mori, Takayasu ; Sohara, Eisei ; Ando, Fumiaki ; Inaba, Shunsuke ; Takahashi, Hidehiko ; Iimori, Soichiro

Chronic kidney disease (CKD) causes cognitive impairment and contributes to the overall global burden of dementia. However, mechanisms through which the kidneys and brain communicate are not fully understood. We established a CKD mouse model through adenine-induced tubulointerstitial fibrosis. Novel object recognition tests indicated that CKD decreased recognition memory. Sarkosyl-insoluble-proteomic analyses of the CKD mouse hippocampus revealed an accumulation of insoluble MAPT (microtubule-associated protein tau) and RNA-binding proteins such as small nuclear ribonucleoprotein U1 subunit 70 (SNRNP70). Additionally, there was an accumulation of Immunoglobulin G (IgG), indicating blood-brain barrier (BBB) breakdown. We identified that expressions of essential tight-junction protein claudin-5 and adherens-junction protein platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) were decreased in the brain endothelial cells of CKD mice. We determined urea as a major uremic solute that dose dependently decreased both claudin-5 and PECAM-1 expression in the mouse brain endothelial cell line bEnd.3 cells. Gelatin zymography indicated that the serum of CKD mice activated matrix metalloproteinase-2 (MMP2), while marimastat ameliorated the reduction of claudin-5 expression by urea in bEnd.3 cells. This study established a brain proteomic signature of CKD indicating BBB breakdown and insolubility of tau protein, which are pathologically linked to Alzheimer's disease. Urea-mediated activation of MMP2 was partly responsible for BBB breakdown in CKD.

30 Sep 2023·bioRxiv : the preprint server for biology

Peptidoglycan from Bacillus anthracis Inhibits Human Macrophage Efferocytosis in Part by Reducing Cell Surface Expression of MERTK and TIM-3.

Author: Redinger, Nancy ; Lawrence, Christina ; Pan, Zijian ; Popescu, Narcis I ; Mytych, Joshua S ; Ziegler, Jadith ; Lopez-Davis, Charmaine ; James, Judith A ; Farris, A Darise

Bacillus anthracis peptidoglycan (PGN) is a major component of the bacterial cell wall and a key pathogen-associated molecular pattern (PAMP) contributing to anthrax pathology, including organ dysfunction and coagulopathy. Increases in apoptotic lymphocytes are a late-stage feature of anthrax and sepsis, suggesting there is a defect in apoptotic clearance. Here, we tested the hypothesis that B. anthracis PGN inhibits the capacity of human monocyte-derived macrophages (MΦ) to efferocytose apoptotic cells. Exposure of CD163⁺CD206⁺ MΦ to PGN for 24h impaired efferocytosis in a manner dependent on human serum opsonins but independent of complement component C3. PGN treatment reduced cell surface expression of the pro-efferocytic signaling receptors MERTK, TYRO3, AXL, integrin αVβ5, CD36 and TIM-3, whereas TIM-1, αVβ3, CD300b, CD300f, STABILIN-1 and STABILIN-2 were unaffected. ADAM17 is a major membrane-bound protease implicated in mediating efferocytotic receptor cleavage. We found multiple ADAM17-mediated substrates increased in PGN-treated supernatant suggesting involvement of membrane-bound proteases. ADAM17 inhibitors TAPI-0 and Marimastat prevented TNF release, indicating effective protease inhibition, and modestly increased cell-surface levels of MerTK and TIM-3 but only partially restored efferocytic capacity by PGN-treated MΦ. We conclude that human serum factors are required for optimal recognition of PGN by human MΦ and that B. anthracis PGN inhibits efferocytosis in part by reducing cell surface expression of MERTK and TIM-3.

01 Aug 2023·Chemistry & biodiversity

Green Synthesis of Genistein‐Fortified Zinc Ferrite Nanoparticles as a Potent Hepatic Cancer Inhibitor: Validation through Experimental and Computational Studies

Article

Author: Jaremko, Mariusz ; Khalilullah, Habibullah ; Otuechere, Chiagoziem A ; Grishina, Maria ; Pathak, Prateek ; Verma, Amita ; Novak, Jurica ; Neupane, Netra P ; Adewuyi, Adewale

Abstract:

In hepatic cancer, precancerous nodules account for damage and inflammation in liver cells. Studies have proved that phyto‐compounds based on biosynthetic metallic nanoparticles display superior action against hepatic tumors. This study targeted the synthesis of genistein‐fortified zinc ferrite nanoparticles (GENP) trailed by anticancer activity assessment against diethylnitrosamine and N‐acetyl‐2‐aminofluorene induced hepatic cancer. The process of nucleation was confirmed by UV/VIS spectrophotometry, X‐ray beam diffraction, field‐emission scanning electron microscopy, and FT‐IR. An in vitro antioxidant assay illustrated that the leaves of Pterocarpus mildbraedii have strong tendency as a reductant and, in the nanoformulation synthesis, as a natural capping agent. A MTT assay confirmed that GENP have a strong selective cytotoxic potential against HepG2 cancer cells. In silico studies of genistein exemplified the binding tendency towards human matrix metalloproteinase comparative to the standard drug marimastat. An in vivo anticancer evaluation showed that GENP effectively inhibit the growth of hepatic cancer by interfering with hepatic and non‐hepatic biochemical markers.

100 Deals associated with Marimastat

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External Link

KEGG	Wiki	ATC	Drug Bank
D03795	Marimastat	-	DB00786

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Non-small cell lung cancer stage III	Phase 3	US	ILEX Oncology Services, Inc.	01 Dec 1996
Non-small cell lung cancer stage III	Phase 3	CA	ILEX Oncology Services, Inc.	01 Dec 1996
Breast Cancer	Phase 3	US	-	-
Glioma	Phase 3	US	-	-
Glioma	Phase 3	EU	-	-
Glioma	Phase 3	CA	-	-
Lung Cancer	Phase 3	-	Merck Sharp & Dohme Corp.	-
Non-Small Cell Lung Cancer	Phase 3	US	-	-
Non-Small Cell Lung Cancer	Phase 3	EU	-	-
Non-Small Cell Lung Cancer	Phase 3	CA	-	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00003010 (E2196, Pubmed \| J Urol)	Phase 3	Metastatic breast cancer First line	-	Marimastat	udczgaibxx(twnpdlmzpl) = Patients with grade 2 or 3 MST had significantly inferior survival compared with patients who had grade 0 or 1 MST (median, 22.5 months v 28.2 months; P = .04) qgddewvxly (ykmdmagbdc ) View more	Negative	01 Dec 2004
				Placebo
NCT00003011 (Pubmed \| J Urol)	Phase 3	Small Cell Lung Cancer Adjuvant	532	Marimastat 10 mg	pmvtdzhboe(vkvdstemul) = aeqpokbfya aergrtdgcu (ijoalfmimi ) View more	Negative	15 Nov 2002
				Placebo	pmvtdzhboe(vkvdstemul) = xklityoxjd aergrtdgcu (ijoalfmimi ) View more