Delving into the Latest Updates on HGS-1029 with Synapse

Overview

Basic Info

Drug Type

Chemical drugs

Synonyms

+ [1]

Target

IAP

Mechanism

Inhibitors of apoptosis (IAP) protein family inhibitors

Therapeutic Areas

NeoplasmsImmune System DiseasesHemic and Lymphatic Diseases

Active Indication-

Inactive Indication

Advanced Malignant Solid NeoplasmLymphomaNeoplasms+ [1]

Originator Organization

Aegera Therapeutics, Inc.

Active Organization-

Inactive Organization

Human Genome Sciences, Inc.

Pharmascience, Inc.

Aegera Therapeutics, Inc.

Drug Highest PhaseDiscontinuedPhase 1

First Approval Date-

Regulation-

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Structure

Molecular FormulaC58H80N10O8

InChIKeyZPZYSWMWQKSQBU-HFMNLVBRSA-N

CAS Registry949963-04-6

Protein-protein interactions (PPI) are involved in virtually every cellular process and thus represent an attractive target for therapeutic interventions. A significant number of protein interactions are frequently formed between globular domains and short linear peptide motifs (DMI). Targeting these DMIs has proven challenging and classical approaches to inhibiting such interactions with small molecules have had limited success. However, recent new approaches have led to the discovery of potent inhibitors, some of them, such as Obatoclax, ABT-199, AEG-40826 and SAH-p53-8 are likely to become approved drugs. These novel inhibitors belong to a wide range of different molecule classes, ranging from small molecules to peptidomimetics and biologicals. This article reviews the main reasons for limited success in targeting PPIs, discusses how successful approaches overcome these obstacles to discovery promising inhibitors for human protein double minute 2 (HDM2), B-cell lymphoma 2 (Bcl-2), X-linked inhibitor of apoptosis protein (XIAP), and provides a summary of the promising approaches currently in development that indicate the future potential of PPI inhibitors in drug discovery.

15 Nov 2015·Clinical Cancer ResearchQ1 · MEDICINE

Promises and Challenges of Smac Mimetics as Cancer Therapeutics

Q1 · MEDICINE

Review

Author: Fulda, Simone

AbstractInhibitor of Apoptosis (IAP) proteins block programmed cell death and are expressed at high levels in various human cancers, thus making them attractive targets for cancer drug development. Second mitochondrial activator of caspases (Smac) mimetics are small-molecule inhibitors that mimic Smac, an endogenous antagonist of IAP proteins. Preclinical studies have shown that Smac mimetics can directly trigger cancer cell death or, even more importantly, sensitize tumor cells for various cytotoxic therapies, including conventional chemotherapy, radiotherapy, or novel agents. Currently, several Smac mimetics are under evaluation in early clinical trials as monotherapy or in rational combinations (i.e., GDC-0917/CUDC-427, LCL161, AT-406/Debio1143, HGS1029, and TL32711/birinapant). This review discusses the promise as well as some challenges at the translational interface of exploiting Smac mimetics as cancer therapeutics. Clin Cancer Res; 21(22); 5030–6. ©2015 AACR.See all articles in this CCR Focus section, “Cell Death and Cancer Therapy.”

15 Jan 2014·Clinical Cancer ResearchQ1 · MEDICINE

Molecular Pathways: Targeting Inhibitor of Apoptosis Proteins in Cancer—From Molecular Mechanism to Therapeutic Application

Q1 · MEDICINE

Review

Author: Fulda, Simone

AbstractInhibitor of apoptosis (IAP) proteins play a critical role in the control of survival and cell death by regulating key signaling events such as caspase activation and NF-κB signaling. Because aberrantly high expression of IAP proteins represents a frequent oncogenic event in human cancers, therapeutic targeting of IAP proteins is considered as a promising approach. Several small-molecule pharmacologic inhibitors of IAP proteins that mimic the binding domain of the endogenous IAP antagonist second mitochondrial activator of caspases (Smac) to IAP proteins have been developed over the past few years. IAP antagonists have been shown in various preclinical cancer models to either directly initiate cell death or, alternatively, to prime cancer cells for cytotoxic therapies by lowering the threshold for cell death induction. IAP antagonists (i.e., GDC-0917/CUDC-427, LCL161, AT-406, HGS1029, and TL32711) are currently under evaluation in early clinical trials alone or in combination regimens. Thus, the concept to therapeutically target IAP proteins in human cancer has in principle been successfully transferred into a clinical setting and warrants further evaluation as a treatment approach. Clin Cancer Res; 20(2); 289–95. ©2013 AACR.

100 Deals associated with HGS-1029

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Lymphoma	Phase 1	US	Human Genome Sciences, Inc.	01 Oct 2009
Lymphoma	Phase 1	GB	Human Genome Sciences, Inc.	01 Oct 2009
Advanced Malignant Solid Neoplasm	Phase 1	US	Human Genome Sciences, Inc.	01 May 2008
Neoplasms	Phase 1	CA	Aegera Therapeutics, Inc.	-
Solid tumor	Phase 1	CA	Pharmascience, Inc.	-