Delving into the Latest Updates on Delanzomib with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Delanzomib (USAN)

+ [7]

Target

Proteasome

Mechanism

Proteasome inhibitors, Apoptosis stimulants

Therapeutic Areas

NeoplasmsImmune System DiseasesCardiovascular Diseases+ [1]

Active Indication

Multiple Myeloma

Inactive Indication

Advanced Malignant Solid NeoplasmSystemic Lupus Erythematosus

Originator Organization

Teva Pharmaceutical Industries Ltd.

Active Organization

Institute For Myeloma & Bone Cancer Research

Inactive Organization

Cephalon, Inc.

EOS (Ethical Oncology Science)

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

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Structure

Molecular FormulaC21H28BN3O5

InChIKeySJFBTAPEPRWNKH-CCKFTAQKSA-N

CAS Registry847499-27-8

This Phase 1 escalating-dose study is designed to assess, the safety, tolerability, pharmacokinetics, and pharmacodynamics of the novel proteasome inhibitor CEP 18770, given intravenously as single agent, in patients with advanced, incurable solid tumours or NHL, and to identify the recommended dose of CEP 18770 to be used in Phase 2 studies.

Start Date01 Nov 2007

Sponsor / Collaborator

EOS (Ethical Oncology Science)

100 Clinical Results associated with Delanzomib

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100 Translational Medicine associated with Delanzomib

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100 Patents (Medical) associated with Delanzomib

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39

Literatures (Medical) associated with Delanzomib

01 Feb 2023·Biological and Pharmaceutical Bulletin

Potential Efficacy of Proteasome Inhibitor, Delanzomib, for the Treatment of Renal Fibrosis

Article

Author: Yamada, Yoshihisa ; Nagao, Goshi ; Ishida, Tatsuhiro ; Hattori, Katsuji ; Sawa-Aihara, Ayano

Renal fibrosis is scarring and tissue hardening caused by the excess deposition of extracellular matrix proteins in response to chronic inflammation. Renal fibrosis is the primary cause of a progressive loss of renal function, and is an important therapeutic target because it ultimately leads to end-stage renal failure, which can be treated only by either dialysis or kidney transplantation. There is no effective treatment that specifically targets renal fibrosis. Myofibroblasts are known to evade apoptosis by activating molecular mechanisms in response to pro-survival biomechanical and growth factor signals from the fibrotic microenvironment. In this study, we screened and selected compounds that selectively cause cell death in myofibroblasts in vitro and studied their possible potency against renal fibrosis in a mouse model. Several proteasome inhibitors induced selective cell death in myofibroblasts differentiated from the human fibroblast cell line (MRC5). The in vivo antifibrotic effect of Delanzomib (Dz), one of the proteasome inhibitors most sensitive to myofibroblasts in vitro, was investigated in a Unilateral Ureteric Obstruction (UUO) mouse model. Treatment with Dz decreased the expression levels of the actin-alpha-2 (ACTA2) and collagen-type-1-alpha-1 (COL1A1) genes in the kidney, which are common fibrosis markers. These results suggest that Dz might be a compound that suppresses renal fibrosis by inducing selective cell death of myofibroblasts, although further investigation is required.

01 Jan 2023·Frontiers in chemistry

Unlocking the potential of approved drugs for the allosteric inhibition of tropomyosin-receptor kinase A using molecular docking and molecular dynamics studies.

Article

Author: Sherif, Asmaa E ; Ghaboosh, Hiba ; Mahgoub, Mohanad A ; Ashour, Ahmed ; Abdelmoniem, Nihal ; Edris, Alaa ; Samman, Waad A ; Garelnabi, Elrashied A E ; Mukhtar, Rua M ; Ibrahim, Sabrin R M ; Mohamed, Gamal A ; Bafail, Rawan ; Osman, Wadah ; Ghazawi, Kholoud F ; Alzain, Abdulrahim A ; Alhaddad, Aisha A ; Elrufaie, Hisham A

Tropomyosin-receptor kinase A (TrkA) is the primary isoform among the tropomyosin-receptor kinases that have been associated with human cancer development, contributing to approximately 7.4% of all cancer cases. TrkA represents an attractive target for cancer treatment; however, currently available TrkA inhibitors face limitations in terms of resistance development and potential toxicity. Hence, the objective of this study was to identify new allosteric-approved inhibitors of TrkA that can overcome these challenges and be employed in cancer therapy. To achieve this goal, a screening of 9,923 drugs from the ChEMBL database was conducted to assess their repurposing potential using molecular docking. The top 49 drug candidates, exhibiting the highest docking scores (-11.569 to -7.962 kcal/mol), underwent MM-GBSA calculations to evaluate their binding energies. Delanzomib and tibalosin, the top two drugs with docking scores of -10.643 and -10.184 kcal/mol, respectively, along with MM-GBSA dG bind values of -67.96 and -50.54 kcal/mol, were subjected to 200 ns molecular dynamic simulations, confirming their stable interactions with TrkA. Based on these findings, we recommend further experimental evaluation of delanzomib and tibalosin to determine their potential as allosteric inhibitors of TrkA. These drugs have the potential to provide more effective and less toxic therapeutic alternatives. The approach employed in this study, which involves repurposing drugs through molecular docking and molecular dynamics, serves as a valuable tool for identifying novel drug candidates with distinct therapeutic uses. This methodology can contribute to reducing the attrition rate and expediting the process of drug discovery.

01 Jan 2023·Frontiers in endocrinology

Proteasome inhibitors in medullary thyroid carcinoma: time to restart with clinical trials?

Review

Author: Modica, Roberta ; Grossrubatscher, Erika Maria ; Fanciulli, Giuseppe ; Florio, Tullio ; Veresani, Alessandro ; Colao, Annamaria ; Ferraù, Francesco ; Russo, Flaminia ; La Salvia, Anna ; Faggiano, Antongiulio

IntroductionMedullary thyroid cancer (MTC) is a rare thyroid tumour whose management in advanced stages is challenging, despite effective therapeutic options having expanded in recent years. Proteasome inhibitors (PrIn) have shown the ability to improve patient outcomes, including survival and quality of life, in several malignancies, due to their ability to impair cell proliferation and cause apoptosis through the inhibition of the proteasome activity. Consequently, these drugs could represent a useful tool, alone or in combination with other treatments, in MTC patients.Aim of the studyThis review aims to summarize the available in vitro and in vivo data about the role of PrIn in MTC.Materials and methodsWe performed an extensive search for relevant data sources, including full-published articles in international online databases (PubMed, Web of Science, Scopus), preliminary reports in selected international meeting abstract repositories, and short articles published as supplements of international meetings, by using the following terms: medullary thyroid carcinoma, proteasome inhibitors, bortezomib, carfilzomib, ixazomib, delanzomib, marizomib, oprozomib, and MG132. Additionally, we conducted with the same keywords, an in-depth search in registered clinical trials repositories.ResultsOur search revealed in vitro studies in human and murine MTC cell lines, based on the use of PrIns, both alone and in combination with other anticancer drugs, and two pertinent clinical trials.ConclusionWe found a strong discrepancy between the evidence of PrIns effects in preclinical studies, and the scarcity or early interruption of clinical trials. We might speculate that difficulties in enrolling patients, as happens in other rare diseases, may have discouraged trials' implementation in favor of drugs already approved for MTC. However, given the concrete improvement in the comprehension of the molecular basis of PrIn effects in MTC, new clinical trials with accurate inclusion criteria of enrollment might be warranted, in order to ascertain whether this treatment, alone or in combination with other drugs, could indeed represent an option to enhance the therapeutic response, and to ultimately improve patients' outcome and survival.

100 Deals associated with Delanzomib

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External Link

KEGG	Wiki	ATC	Drug Bank
D10110	-	-	DB11956

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Multiple Myeloma	Preclinical	US	Cephalon, Inc.	01 Jan 2010
Advanced Malignant Solid Neoplasm	Discovery	IT	EOS (Ethical Oncology Science)	01 Nov 2007
Advanced Malignant Solid Neoplasm	Discovery	CH	EOS (Ethical Oncology Science)	01 Nov 2007
Non-Hodgkin Lymphoma	Discovery	CH	EOS (Ethical Oncology Science)	01 Nov 2007
Non-Hodgkin Lymphoma	Discovery	IT	EOS (Ethical Oncology Science)	01 Nov 2007
Systemic Lupus Erythematosus	Discovery	US	-	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01348919 (CTgov)	Phase 1/2	Plasma cell myeloma refractory	11	Lenalidomide+CEP-18770+Dexamethasone (CEP-18770 Dose B)	ucexpaondj(xyklgafzlz) = lgojogavcj mqnotbpwyx (xhacztmykn, doghsujhwm - puqcicngkj) View more	-	28 Jun 2023
				Lenalidomide+CEP-18770+Dexamethasone (CEP-18770 Dose A)	byyseolfyc(rgahzbbjto) = qblpjfiawi stngzgpjlm (knhrnyylri, ofdewyxfzy - aswrnkkcgu) View more
NCT01023880 (Pubmed \| Leukemia) Manual	Phase 1/2	Multiple Myeloma	105	Delanzomib (during dose escalation)	(vtipnwyjjt) = cxsaqszktv zwzxihovoy (anpzsrhghk ) View more	Negative	01 Aug 2017
				Delanzomib (expansion cohort)	(vtipnwyjjt) = ohkquowxeu zwzxihovoy (anpzsrhghk ) View more