Delving into the Latest Updates on RX-0201 with Synapse

Overview

Basic Info

Drug Type

ASO

Synonyms

+ [2]

Target

Akt-1

Mechanism

AKT1 gene inhibitors(Serine/threonine-protein kinase AKT gene inhibitors)

Therapeutic Areas

NeoplasmsDigestive System DisordersEndocrinology and Metabolic Disease+ [1]

Active Indication-

Inactive Indication

Advanced Renal Cell CarcinomaMetastatic Renal Cell CarcinomaPancreatic Cancer+ [2]

Originator Organization

Rexahn Pharmaceuticals, Inc.

Active Organization-

Inactive Organization

Zhejiang Haichang Bio-Tech Co., Ltd.

Rexahn Pharmaceuticals, Inc.

NOVAREX Co., Ltd.

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

Login to view timeline

Structure

Boost your research with our RNA technology data.

login

or

view full example data

Boost your research with our RNA technology data.

Gene Sequence

Sequence Code 29415427

Source: *****

Expression of Bcl-2 and Akt-1 has been associated with human cancer. G3139 and RX-0201, targeting Bcl-2 and Akt-1, respectively, are antisense oligonucleotides (ASOs) that have shown limited efficacy in clinical trials. Herein, we report a combination of newly designed ASOs based on these agents and was delivered by tumor cell-targeting lipid nanoparticles (LNPs). A "Gapmer" design strategy was applied to these ASOs with the addition of 2'-O-methyl modifications on the nucleotides at 5' and 3' ends. A dual-channel syringe pump-based system was developed for the synthesis of the LNPs. ASO-LNPs composed of DODMA, egg PC, cholesterol, T7-PEG-DSPE, and PEG-DMG at a molar ratio of 35:39.5:20:0.5:5 and carrying either individual ASOs or co-loaded ASO combinations (Co-ASOs) were synthesized and evaluated in both KB and A549 cancer cells and in an A549 murine xenograft model to determine their antitumor effects and biological activities. The ASO-LNPs exhibited excellent colloidal stability and high ASO encapsulation efficiency with relatively small mean particle sizes and moderately positive zeta potentials. Transferrin receptor-targeting T7-conjugated LNPs showed enhanced cellular uptake compared to nontargeted LNPs. In addition, both T7-conjugated Co-ASOs-LNPs and non-T7-conjugated Co-ASOs-LNPs at a molar ratio of (G3139-GAP to RX-0201-GAP at 1:2) showed efficient downregulation of both Bcl-2 and Akt-1 in both A549 and KB cells. Furthermore, T7-conjugated Co-ASOs-LNPs (Co-ASOs-LNPs) produced superior antitumor activity, prolonged the overall survival time, and demonstrated tumor targeting activity in an A549 xenograft model.

28 May 2018·Journal of Drug TargetingQ3 · MEDICINE

Folate receptor-targeted lipid-albumin nanoparticles (F-LAN) for therapeutic delivery of an Akt1 antisense oligonucleotide

Q3 · MEDICINE

Article

Author: Kim, Deog Joong ; Lee, Robert J. ; Ahn, Chang-Ho ; Cheng, Xinwei ; Lee, Young B. ; Chen, Lihua ; Qi, Shanshan ; Li, Hong ; Liu, Qibing ; Liu, Yang

BACKGROUNDRX-0201 is an antisense oligonucleotide (ASO) against Akt1 currently in clinical trial for metastatic renal cancer.PURPOSETo improve the delivery of RX-0201 using folate receptor-targeted lipid-albumin nanoparticles (F-LAN).METHODSF-LAN were synthesized with the composition of DOTAP/soyPC/TPGS/folate-PEG-DSPE (25:70:4:1 m/m), a cationic human serum albumin-pentaethylenehexamine (HSA-PEHA) conjugate and RX-0201. The nanoparticles were evaluated in KB human carcinoma cells in vitro and in a KB murine xenograft tumour model in vivo for pharmacokinetics and antitumor activities.RESULTSThe F-LAN-RX-0201 had a mean particle size of 108.6 ± 5.8 nm, zeta potential of 10.5 ± 3.2 mV and ASO loading efficiency of 71.5 ± 4.5%. In KB cells, uptake and Akt1 inhibition by F-LAN-RX-0201 were greater than those of non-targeted LAN-RX-0201 and could be partially blocked by excess free folate. F-LAN-RX-0201 inhibited cell growth with an IC₅₀ of 11.9 μM. In contrast, LAN-RX-0201 showed lower cytotoxicity with an IC₅₀ of 32.0 μM. No significant cytotoxicity was observed with up to 250 µM of free RX-0201. Pharmacokinetic studies showed that F-LAN-RX-0201 had a longer terminal half-life than free RX-0201 (442 vs. 219 min). In a KB xenograft tumour model, F-LAN-RX-0201 exhibited greater tumour inhibition than LAN-RX-0201 at 16 mg/kg. Moreover, F-LAN-RX-0201 at 16 mg/kg showed comparable tumour inhibition compared to free RX-0201 at a much higher dose of 90 mg/kg.CONCLUSIONSF-LAN-RX-0201 showed promise as a therapeutic agent for tumours with elevated folate-receptor expression.

01 Nov 2010·Expert Opinion on Investigational DrugsQ2 · MEDICINE

Akt inhibitors in clinical development for the treatment of cancer

Q2 · MEDICINE

Review

Author: Karen Reckamp ; Robert A Figlin ; Sumanta Kumar Pal ; Hua Yu

IMPORTANCE OF THE FIELDThe evolution of targeted therapies is dependent upon identification of cellular moieties that can be pharmacologically modulated. As one such example, the serine-threonine kinase Akt was identified nearly two decades ago. Since then, its role in mediating multiple signaling cascades (ultimately leading to cell growth and proliferation) has since been identified. More recently, several agents have been developed that antagonize Akt--these agents are in various stages of clinical testing.AREAS COVERED IN THIS REVIEWHerein, we outline development of several promising Akt inhibitors, including perifosine, MK-2206, RX-0201, PBI-05204, GSK2141795 and others.WHAT THE READER WILL GAINThe reader will gain insight into the current pipeline of Akt inhibitors, and the degree to which these agents have been examined both clinically and preclinically.TAKE HOME MESSAGEWith an emerging pipeline of agents targeting Akt, it will be critical to decipher which amongst them holds the greatest promise. Herein, we explore this drug pipeline and provide strategies for determining the future clinical application of these agents.

100 Deals associated with RX-0201

Login to view more data

External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB05971

R&D Status

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Advanced Renal Cell Carcinoma	Phase 2	US	Rexahn Pharmaceuticals, Inc.	01 Aug 2014
Metastatic Renal Cell Carcinoma	Phase 2	US	Rexahn Pharmaceuticals, Inc.	01 Aug 2014
Renal Cell Carcinoma	Phase 2	US	Rexahn Pharmaceuticals, Inc.	01 Aug 2014
Secondary malignant neoplasm of pancreas	Phase 2	IN	Rexahn Pharmaceuticals, Inc.	01 May 2009
Secondary malignant neoplasm of pancreas	Phase 2	US	Rexahn Pharmaceuticals, Inc.	01 May 2009
Pancreatic Cancer	Phase 2	-	NOVAREX Co., Ltd.	-
Pancreatic Cancer	Phase 2	-	Zhejiang Haichang Bio-Tech Co., Ltd.	-

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02089334 (CTgov)	Phase 1/2	Metastatic Renal Cell Carcinoma \| Advanced Renal Cell Carcinoma	24	Everolimus+RX-0201 (125 mg/m^2/Day RX-0201 + Everolimus (Stage 1))	oiqabjkble(dhowyjghav) = cdcgqpzaow izpkxiwbfx (hrmixegvwj, vqrmjogvpz - tadxqpmwbo) View more	-	30 Jun 2020
NCT02089334 (CTgov)	Phase 1/2		24	Everolimus+RX-0201 (200 mg/m^2/Day RX-0201 + Everolimus (Stage 1))	oiqabjkble(dhowyjghav) = spkyroufxp izpkxiwbfx (hrmixegvwj, crmaqgdggc - aejdaddtsi) View more	-	30 Jun 2020
NCT02089334 (ASCO_GU2019) Manual	Phase 2	Metastatic Renal Cell Carcinoma	11	everolimus+RX-0201	(fhxjefovwr) = xgulwzzktc wfwhdjgwyt (spvbsuhtvn ) View more	Positive	16 Feb 2019
AACR2016	Phase 2	Metastatic Clear Cell Renal Cell Carcinoma	10	RX-0201 + everolimus	vckhfjaggy(vjzffhmovo) = The most common toxicities attributed to the combination were facial edema sfyrfezmif (rafrvzatfa ) View more	Positive	15 Jul 2016
ASCO2007	Phase 1	Advanced cancer	17	RX-0201	(dberqacdtg) = pxnjsrmvdp cyczunjisv (wtejzcjjxr )	-	20 Jun 2007
ASCO2006	Phase 1	Metastatic Solid Tumor	9	RX-0201	brjctwuxzj(fvettdurpc) = Grade 1 arlxtmeoxs (budzbfxufe ) View more	-	20 Jun 2006