Delving into the Latest Updates on CGC-11047 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target-

Mechanism

Apoptosis stimulants

Therapeutic Areas

NeoplasmsUrogenital DiseasesImmune System Diseases+ [6]

Active Indication-

Inactive Indication

Originator Organization

Cellgate, Inc.

Active Organization-

Inactive Organization

Progen Pharmaceuticals, Inc.Epi-Cure Pharmaceuticals, Inc.

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC14H36Cl4N4

InChIKeyMNJCMBNLXQCNHO-YGGCHVFLSA-N

CAS Registry206991-64-2

View All Structures (2)

RATIONALE: Drugs used in chemotherapy, such as SL-11047, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing.
PURPOSE: This phase I trial is studying the side effects and best dose of SL-11047 in treating patients with relapsed or refractory lymphoma.

Start Date01 Jan 2006

Sponsor / Collaborator

Progen Pharmaceuticals, Inc.

[+1]

100 Clinical Results associated with CGC-11047

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100 Translational Medicine associated with CGC-11047

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100 Patents (Medical) associated with CGC-11047

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14

Literatures (Medical) associated with CGC-11047

01 Jan 2021·Cancer Chemotherapy and PharmacologyQ4 · MEDICINE

A Phase Ib multicenter, dose-escalation study of the polyamine analogue PG-11047 in combination with gemcitabine, docetaxel, bevacizumab, erlotinib, cisplatin, 5-fluorouracil, or sunitinib in patients with advanced solid tumors or lymphoma

Q4 · MEDICINE

Article

Author: Garbo, Lawrence E ; Becerra, Carlos H Roberto ; Stephenson, Joe J ; Richards, Donald A ; Wu, Hillary H ; Von Hoff, Daniel ; Casero, Robert A ; Vogelzang, Nicholas J ; Murray Stewart, Tracy ; Boyd, Thomas E ; Smith, David A ; Jotte, Robert M ; Fitzgerald, Michael ; Marton, Laurence J ; Conkling, Paul R

PURPOSEPolyamines are absolutely essential for maintaining tumor cell proliferation. PG-11047, a polyamine analogue, is a nonfunctional competitor of the natural polyamine spermine that has demonstrated anticancer activity in cells and animal models of multiple cancer types. Preclinical investigations into the effects of common chemotherapeutic agents have revealed overlap with components of the polyamine metabolic pathway also affected by PG-11047. This report describes a Phase Ib clinical trial investigating PG-11047 in combination with cytotoxic and anti-angiogenic chemotherapeutic agents in patients with advanced refractory metastatic solid tumors or lymphoma.METHODSA total of 172 patients were assigned to treatment arms based on cancer type to receive the appropriate standard-of-care therapy (gemcitabine, docetaxel, bevacizumab, erlotinib, cisplatin, 5-fluorouracil (5-FU), or sunitinib as directed) along with once weekly intravenous infusions of PG-11047. PG-11047 dose escalation ranged from 50 to 590 mg.RESULTSThe maximum tolerated dose (MTD) of PG-11047 in combination with bevacizumab, erlotinib, cisplatin, and 5-FU was 590 mg. Dose-limiting toxicities (DLTs) in these groups were rare (5 of 148 patients). Overall partial responses (PR) were observed in 12% of patients treated with PG-11047 and bevacizumab, with stable disease documented in an additional 40%. Stable disease occurred in 71.4% of patients in the 5-FU arm, 54.1% in the cisplatin arm, and 33.3% in the erlotinib arm. Four of the patients receiving cisplatin + PG-11047 (20%) had unconfirmed PRs. MTDs for gemcitabine, docetaxel, and sunitinib could not be determined due to DLTs at low doses of PG-11047 and small sample size.CONCLUSIONSResults of this Phase Ib trial indicate that PG-11047 can be safely administered to patients in combination with bevacizumab, erlotinib, cisplatin, and 5-FU on the once weekly dosing schedule described and may provide therapeutic benefit. The manageable toxicity profile and high MTD determination provide a safety profile for further clinical studies.

01 Jun 2020·Cancer Chemotherapy and PharmacologyQ4 · MEDICINE

A phase I dose-escalation study of the polyamine analog PG-11047 in patients with advanced solid tumors

Q4 · MEDICINE

Article

Author: Casero, Robert A ; Desai, Apurva A ; Fitzgerald, Michael L ; Marton, Laurence J ; Murray Stewart, Tracy

PURPOSEPolyamines are essential for the sustained proliferation and biomass required by tumor cells. Bis-alkylated polyamine analogs are nonfunctional competitors of natural polyamines. Of these, PG-11047, a second-generation unsaturated analog of the polyamine spermine, has demonstrated anticancer activity in cell lines and animal models of multiple cancer types. This report describes the first phase I clinical trial to investigate PG-11047 in patients with advanced refractory metastatic solid tumors.METHODSForty-six patients were treated with 60-min intravenous infusions of PG-11047 using a 28-day dosing cycle with treatments on days 1, 8, and 15. Doses ranged from 50 to 750 mg. The treatment period consisted of at least two cycles.RESULTSThe maximum tolerated dose of PG-11047 administered at this dosing schedule was 610 mg. Dose-limiting toxicities (DLT) were mainly gastrointestinal, including oral/anal mucositis and diarrhea; other DLTs included one case each of angioedema and a grade 3 alanine aminotransferase (ALT) increase. The most common adverse effects were fatigue and anorexia. Stable disease was documented in 30% of patients.CONCLUSIONResults of this phase I trial suggest that PG-11047 can be safely administered to patients on the once weekly dosing schedule described. The manageable toxicity profile and high MTD determination provide a safety profile for further clinical studies, including those in combination with current chemotherapeutic agents.

04 Sep 2018·Molecular PharmaceuticsQ2 · MEDICINE

Polymeric Prodrugs Targeting Polyamine Metabolism Inhibit Zika Virus Replication

Q2 · MEDICINE

Article

Author: Xie, Ying ; Dunworth, Matthew ; Casero, Robert A. ; Oupicky, David ; Routhu, Nanda Kishore ; Byrareddy, Siddappa N.

The Zika virus (ZIKV) is primarily transmitted via an infected mosquito bite, during sexual intercourse, or in utero mother to child transmission. When a fetus is infected, both neurological malformations and deficits in brain development are frequently manifested. As such, there is a need for vaccines or drugs that may be used to cure ZIKV infections. Metabolic pathways play a crucial role in cell differentiation and development. More importantly, polyamines play a key role in replication and translation of several RNA viruses, including ZIKV, Dengue virus, and Chikungunya virus. Here, we present polyamine analogues (BENSpm and PG11047) and their corresponding polymer prodrug derivatives for inhibiting ZIKV infection by intersecting with polyamine catabolism pathways. We tested the compounds against ZIKV African (MR766) and Asian (PRVABC59) strains in human kidney epithelial (Vero) and glioblastoma derived (SNB-19) cell lines. Our results demonstrate potent inhibition of ZIKV viral replication in both cell lines tested. This antiviral effect was mediated by the upregulation of two polyamine catabolic enzymes, spermine oxidase, and spermidine (SMOX)/spermine N1-acetyltransferase (SAT1) as apparent reduction of the ZIKV infection following heterologous expression of SMOX and SAT1. On the basis of these observations, we infer potential use of these polyamine analogues to treat ZIKV infections.

100 Deals associated with CGC-11047

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB05722

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Age Related Macular Degeneration	Phase 2	US	Progen Pharmaceuticals, Inc.	01 Apr 2007
Age Related Macular Degeneration	Phase 2	MX	Progen Pharmaceuticals, Inc.	01 Apr 2007
Age Related Macular Degeneration	Phase 2	RU	Progen Pharmaceuticals, Inc.	01 Apr 2007
Glycogen Storage Disease Type II	Phase 2	US	Progen Pharmaceuticals, Inc.	01 Apr 2007
Glycogen Storage Disease Type II	Phase 2	RU	Progen Pharmaceuticals, Inc.	01 Apr 2007
Glycogen Storage Disease Type II	Phase 2	MX	Progen Pharmaceuticals, Inc.	01 Apr 2007
Metastatic castration-resistant prostate cancer	Phase 2	US	Progen Pharmaceuticals, Inc.	01 Jun 2006
Refractory Lymphoma	Phase 2	US	Progen Pharmaceuticals, Inc.	01 Jan 2006
Recurrent Lymphoma	Discovery	US	Progen Pharmaceuticals, Inc.	01 Jan 2006
Solid tumor	Discovery	US	Epi-Cure Pharmaceuticals, Inc.	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00705653 (Pubmed \| Cancer Chemother Pharmacol)	Phase 1	HR-positive/HER2-low Solid Tumors	46	PG-11047	(wvaxeswwto) = pdrmhsfzer mdmjfhczmn (fpqkyvdufp ) View more	-	01 Jun 2020
NCT00446654 (CTgov)	Phase 1	Age Related Macular Degeneration \| Glycogen Storage Disease Type II	43	CGC-11047 (CGC-11047 Once Every 2 Weeks)	mecanfjspj(dxpxgnahow) = ccvymcjxro irsnoctvsx (qsqkikfwka, adjuusdtpj - vhuhgeirzu) View more	-	06 Aug 2012
NCT00446654 (CTgov)	Phase 1		43	CGC-11047 (CGC-11047 Once Every Four Weeks)	mecanfjspj(dxpxgnahow) = sixioebwmd irsnoctvsx (qsqkikfwka, qvpywdravd - mqbiewghtu) View more	-	06 Aug 2012
NCT00705653 (CTgov)	Phase 1	Solid tumor	46	PG-11047	mydzkqvsui(icchmxrntl) = cogokzljqj gpbhxlvehj (vegwfrqbnq, ierzhahyar - jbrrshwvgb) View more	-	27 Feb 2012