Delving into the Latest Updates on Anecortave Acetate with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Anacortave, Anecortave, Anecortave acetate (JAN/USAN)

+ [6]

Target

VEGF

Mechanism

VEGF inhibitors(Vascular endothelial growth factor inhibitors)

Therapeutic Areas

Nervous System DiseasesCongenital DisordersEndocrinology and Metabolic Disease+ [4]

Active Indication-

Inactive Indication

Central Serous ChorioretinopathyChoroidal NeovascularizationDiabetic Retinopathy+ [15]

Originator Organization

Alcon AG

Active Organization-

Inactive Organization

Alcon Research Ltd.

Drug Highest PhaseDiscontinuedPhase 3

First Approval Date-

RegulationOrphan Drug (JP)

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Structure

Molecular FormulaC23H30O5

InChIKeyYUWPMEXLKGOSBF-GACAOOTBSA-N

CAS Registry7753-60-8

This study will investigate the use of anecortave acetate injection to reduce intraocular pressure (IOP) in corneal transplant recipients who are experiencing steroid-associated pressure control problems. Alternative methods of IOP control have been shown to entail serious risks. For example, reduction of topical steroids increases the risk of graft rejection, and use of glaucoma medications or glaucoma surgery increases the risk of graft failure. This study is designed to have sufficient power to detect whether a single injection can induce a clinically significant IOP reduction.

Start Date01 May 2009

Sponsor / Collaborator

Cornea Research Foundation of America , Inc.

NCT00788541 / TerminatedPhase 2

A Dose-Volume Study of the Safety and IOP-Lowering Efficacy of Anecortave Acetate in Patients With Open-Angle Glaucoma or Ocular Hypertension

The purpose of this study was to assess the effects of total volume and total dose on the safety and intraocular pressure-lowering efficacy of Anecortave Acetate Suspension (3 mg and 48 mg) in 0.5 mL and 0.8 mL volumes when administered by anterior juxtascleral depot (AJD) for the treatment of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension.

Start Date01 Dec 2008

Sponsor / Collaborator

Alcon Research Ltd.

NCT00691717 / CompletedPhase 2/3

A Study of the Safety and IOP-Lowering Efficacy of Anecortave Acetate in Patients With Open-Angle Glaucoma or Ocular Hypertension

The purpose of this study was to evaluate the safety and intraocular-lowering efficacy of anecortave acetate depot when administered by anterior juxtascleral depot (AJD) for the treatment of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension.

Start Date01 Jun 2008

Sponsor / Collaborator

Alcon Research Ltd.

100 Clinical Results associated with Anecortave Acetate

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100 Translational Medicine associated with Anecortave Acetate

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100 Patents (Medical) associated with Anecortave Acetate

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74

Literatures (Medical) associated with Anecortave Acetate

01 Sep 2013·Expert Review of Clinical PharmacologyQ2 · MEDICINE

Update on current and future novel therapies for dry age-related macular degeneration

Q2 · MEDICINE

Review

Author: Ella Leung ; Gennady Landa

Age-related macular degeneration (ARMD) is the leading cause of irreversible blindness in developed countries. There are currently no cures, but there are promising potential therapies that target the underlying disease mechanisms of dry ARMD. Stem cells, ciliary neurotrophic factor, rheopheresis, ozonated autohemotherapy and prostaglandins show promise in stabilizing or improving visual acuity. Age-Related Eye Disease Study vitamins may reduce progression to severe ARMD. Adjuvant therapy like low vision rehabilitation and implantable miniature telescopes may help patients adjust to the sequelae of their disease, and herbal supplementation with saffron, zinc monocysteine and phototrop may be helpful. Therapies that are currently in clinical trials include brimonidine, doxycycline, anti-amyloid antibodies (GSK933776 and RN6G), RPE65 inhibitor (ACU-4429), complement inhibitors (ARC1905, FCFD4514S), hydroxychloroquine, intravitreal fluocinolone acetate and vasodilators like sildenafil, moxaverine and MC-1101. Therapies that have not been shown to be effective include POT-4, eculizumab, tandospirone, anecortave acetate, the antioxidant OT-551, sirolimus and vitamin E.

01 Apr 2013·Bioorganic & Medicinal ChemistryQ3 · MEDICINE

VBP15: Preclinical characterization of a novel anti-inflammatory delta 9,11 steroid

Q3 · MEDICINE

Article

Author: John M. McCall ; Erica K.M. Reeves ; Eric P. Hoffman ; Jesse M. Damsker ; Kanneboyina Nagaraju

Δ9,11 modifications of glucocorticoids (21-aminosteroids) have been developed as drugs for protection against cell damage (lipid peroxidation; lazaroids) and inhibition of neovascularization (anecortave). Part of the rationale for developing these compounds has been the loss of glucocorticoid receptor binding due to the Δ9,11 modification, thus avoiding many immunosuppressive activities and deleterious side effect profiles associated with binding to glucocorticoid and mineralocorticoid receptors. We recently demonstrated that anecortave acetate and its 21-hydroxy analog (VBP1) do, in fact, show glucocorticoid and mineralocorticoid receptor binding activities, with potent translocation of the glucocorticoid receptor to the cell nucleus. We concluded that Δ9,11 steroids showed novel anti-inflammatory properties, retaining NF-κB inhibition, but losing deleterious glucocorticoid side effect profiles. Evidence for this was developed in pre-clinical trials of chronic muscle inflammation. Here, we describe a drug development program aimed at optimizing the Δ9,11 chemistry. Twenty Δ9,11 derivatives were tested in in vitro screens for NF-κB inhibition and GR translocation to the nucleus, and low cell toxicity. VBP15 was selected as the lead compound due to potent NF-κB inhibition and GR translocation similar to prednisone and dexamethasone, lack of transactivation properties, and good bioavailability. Phamacokinetics were similar to traditional glucocorticoid drugs with terminal half-life of 0.35 h (mice), 0.58 h (rats), 5.42 h (dogs), and bioavailability of 74.5% (mice), and 53.2% (dogs). Metabolic stability showed ≥80% remaining at 1 h of VBP6 and VBP15 in human, dog, and monkey liver microsomes. Solubility, permeability and plasma protein binding were within acceptable limits. VBP15 moderately induced CYP3A4 across the three human hepatocyte donors (24-42%), similar to other steroids. VBP15 is currently under development for treatment of Duchenne muscular dystrophy.

15 Mar 2013·ACS Chemical BiologyQ2 · BIOLOGY

Identification of PDE6D as a Molecular Target of Anecortave Acetate via a Methotrexate-Anchored Yeast Three-Hybrid Screen

Q2 · BIOLOGY

Article

Author: Shepard, Allan R. ; Rutschmann, Katrin ; Rezwan, Mandana ; SriRamaratnam, Rohitha ; Cornish, Virginia W. ; Auerbach, Daniel ; Jacobson, Nasreen ; Conrow, Raymond E. ; Pang, Iok-Hou

Glaucoma and age-related macular degeneration are ocular diseases targeted clinically by anecortave acetate (AA). AA and its deacetylated metabolite, anecortave desacetate (AdesA), are intraocular pressure (IOP)-lowering and angiostatic cortisenes devoid of glucocorticoid activity but with an unknown mechanism of action. We used a methotrexate-anchored yeast three-hybrid (Y3H) technology to search for binding targets for AA in human trabecular meshwork (TM) cells, the target cell type that controls IOP, a major risk factor in glaucoma. Y3H hits were filtered by competitive Y3H screens and coimmunoprecipitation experiments and verified by surface plasmon resonance analysis to yield a single target, phosphodiesterase 6-delta (PDE6D). PDE6D is a prenyl-binding protein with additional function outside the PDE6 phototransduction system. Overexpression of PDE6D in mouse eyes caused elevated IOP, and this elevation was reversed by topical ocular application of either AA or AdesA. The identification of PDE6D as the molecular binding partner of AA provides insight into the role of this drug candidate in treating glaucoma.

100 Deals associated with Anecortave Acetate

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External Link

KEGG	Wiki	ATC	Drug Bank
D01733	Anecortave Acetate	S01LA02	DB05288

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Glaucoma, Open-Angle	Phase 3	US	Alcon Research Ltd.	01 Jun 2008
Hypertension	Phase 3	US	Alcon Research Ltd.	01 Jun 2008
Glycogen Storage Disease Type II	Phase 3	US	Alcon Research Ltd.	01 Jun 2003
Choroidal Neovascularization	Phase 3	US	Alcon Research Ltd.	01 Mar 2003
Wet age-related macular degeneration	Phase 3	US	Alcon Research Ltd.	01 Mar 2003
Wet Macular Degeneration	Phase 3	US	Alcon Research Ltd.	01 Jun 2002
Diabetic Retinopathy	Phase 3	US	Alcon Research Ltd.	01 Mar 2002
Inflammation	Phase 3	US	Alcon Research Ltd.	01 Mar 2002
Rubeotic iris	Phase 3	US	Alcon Research Ltd.	01 Mar 2002
Retinal Telangiectasis	Phase 2	US	Alcon Research Ltd.	01 Mar 2002

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00884039 (CTgov)	Not Applicable	-	7	30 mg anecortave acetate (30 mg Anecortave Acetate)	fgzoqrifxu(leccfjtvxe) = evbivgxvsj nvttnwibds (fkgggprmmg, kkgfyslmuz - onoqcvjvub) View more	-	17 Nov 2010
				anecortave acetate (15 mg Anecortave Acetate)	fgzoqrifxu(leccfjtvxe) = mvfctazpee nvttnwibds (fkgggprmmg, arcwrxbkbs - gplvsodscq) View more
ARVO2010	Not Applicable	Ocular Hypertension	16	Anecortave Acetate	(csevqbwkgj) = eeyhrrmrou zmlhudrdpw (lwlfeirfwy ) View more	-	01 Apr 2010
				Prednisolone Acetate	(csevqbwkgj) = ygazqctsdq zmlhudrdpw (lwlfeirfwy ) View more
AAO2008	Not Applicable	Glaucoma, Open-Angle	-	Anecortave Acetate 7.5 mg	(wqcqhgiidb) = bmxqqwhwvs vrtpwsrrkn (ugtqxdsgir )	Positive	10 Nov 2008
				Anecortave Acetate 15 mg	(wqcqhgiidb) = boekklsctw vrtpwsrrkn (ugtqxdsgir )
RFC012007 (ARVO2008)	Not Applicable	Age Related Macular Degeneration	20	Anecortave acetate	(yibgbeyqmi) = ekxpojyvvk gdtderlkqi (dijtnlxbiy )	-	01 May 2008
ARVO2008	Not Applicable	Glaucoma, Open-Angle	86	Anecortave Acetate 3 mg	(oungdajjzg) = Of the 14 reports of eye pain, 9 (64%) were related to the injection procedure. aqzxuejnlx (khcendzqvg )	Positive	01 May 2008
				Anecortave Acetate 15 mg
ARVO2007	Not Applicable	-	-	Anecortave acetate	wicvrfcdyk(dylxwrigfe) = tolznaxdbx mdkrisjxqn (ooazudhmyt )	-	01 May 2007
PA097 (AAO2006)	Not Applicable	Glaucoma, Open-Angle	6	Anecortave Acetate	(ojaopovngn) = no significant adverse events fdvetejrdv (wikkgvznoz )	Positive	14 Nov 2006
PO287 (AAO2006)	Not Applicable	Ocular Hypotension	8	Anecortave Acetate 3 mg	(plqjiuwgvq) = xzmqkmpiwl osbslqbhag (pswuamktol, 5.1)	Positive	12 Nov 2006
				Anecortave Acetate 12 mg	(plqjiuwgvq) = ophvxznoyn osbslqbhag (pswuamktol, 5.1)
ARVO2006	Not Applicable	Glaucoma	3	Anecortave Acetate	(afrnfiyumu) = mxsifmqjfi fntbwsbbce (mqhbafgivg )	Positive	01 May 2006
ARVO2006	Not Applicable	Glaucoma, Open-Angle	6	Anecortave acetate	(rwclcqdzwn) = wnuoaokeqc fjfwddwenn (pavqyexaao, 6)	-	01 May 2006