Delving into the Latest Updates on (9Z)-UAB-30 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

RETINOID 9CUAB30

+ [2]

Target

RXRA

Mechanism

RXRA agonists(Retinoid X receptor alpha agonists)

Therapeutic Areas

NeoplasmsSkin and Musculoskeletal Diseases

Active Indication

Early Stage Breast CarcinomaInvasive Mammary CarcinomaNoninfiltrating Intraductal Carcinoma+ [1]

Inactive Indication

Skin Neoplasms

Originator Organization

The University of Alabama at Birmingham

Active Organization

National Cancer Institute

The University of Alabama at Birmingham

Inactive Organization-

Drug Highest PhasePhase 1

First Approval Date-

Regulation-

Structure

Molecular FormulaC20H22O2

InChIKeyPPGNMFUMZSAZCW-VOYUZAMQSA-N

CAS Registry205252-57-9

This is a randomized, double-blind, placebo-controlled biomarker study in renal transplant recipients with actinic damage and a history of basal cell carcinomas and/or cutaneous squamous cell carcinomas. There will be two arms to the study: 1) daily oral UAB30 for 28 days; and 2) daily oral placebo for 28 days. The total duration of the study is anticipated to be 5 years. The hypothesis being tested is that a significantly greater percentage of subjects randomized to oral UAB30 over a period of 28 days will achieve ≥30% reduction in biomarkers of proliferation and ≥30% increase in apoptosis biomarkers than those who receive placebo. Cyclin D1 will serve as the primary biomarker.
This investigation will determine whether subjects randomized to UAB30 have an increase in all trans-retinoic acid responsive genes in the skin compared to those receiving placebo. This will include an examination of target effects of UAB30 by evaluating its effects in vivo in humans on the DNA damage response and Src signaling pathways.

Start Date01 Oct 2020

Sponsor / Collaborator

The University of Alabama at Birmingham

NCT02876640 / Active, not recruitingPhase 1IIT

Phase Ib 9cUAB30 in Early Stage Breast Cancer to Evaluate Biologic Effect

This phase 1b trial studies the biologic effect of 9cUAB30 on early stage breast cancer. 9cUAB30 is a retinoid X receptor (RXR)-selective retinoid that acts in a tissue selective manner with the goal of minimizing side effects, a necessary feature of agents under development for cancer prevention.

Start Date16 Mar 2018

Sponsor / Collaborator

National Cancer Institute

NCT01935960 / CompletedPhase 1IIT

A Randomized, Double-Blind, Phase I Dose-Escalation Study of the Novel Retinoid 9cUAB30

This randomized phase I trial studies the side effects and best dose of retinoid 9cUAB30 in preventing cancer in healthy volunteers. The use of retinoid 9cUAB30 may keep cancer from forming in healthy volunteers.

Start Date01 Aug 2013

Sponsor / Collaborator

National Cancer Institute

100 Clinical Results associated with (9Z)-UAB-30

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100 Translational Medicine associated with (9Z)-UAB-30

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100 Patents (Medical) associated with (9Z)-UAB-30

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34

Literatures (Medical) associated with (9Z)-UAB-30

01 Jan 2023·Journal of Biological Chemistry

Next-generation retinoid X receptor agonists increase ATRA signaling in organotypic epithelium cultures and have distinct effects on receptor dynamics

Article

Author: Nagy, Laszlo ; Berger, Wilhelm K ; Halasz, Laszlo ; Pilli, Nagesh ; Melo, Nathalia ; Yang, Zhengrong ; Kedishvili, Natalia Y ; Elmets, Craig A ; Belyaeva, Olga V ; Muccio, Donald D ; Atigadda, Venkatram ; Yu, Jianshi ; Kane, Maureen A ; Renfrow, Matthew B ; Klyuyeva, Alla V

Retinoid X receptors (RXRs) are nuclear transcription factors that partner with other nuclear receptors to regulate numerous physiological processes. Although RXR represents a valid therapeutic target, only a few RXR-specific ligands (rexinoids) have been identified, in part due to the lack of clarity on how rexinoids selectively modulate RXR response. Previously, we showed that rexinoid UAB30 potentiates all-trans-retinoic acid (ATRA) signaling in human keratinocytes, in part by stimulating ATRA biosynthesis. Here, we examined the mechanism of action of next-generation rexinoids UAB110 and UAB111 that are more potent in vitro than UAB30 and the FDA-approved Targretin. Both UAB110 and UAB111 enhanced ATRA signaling in human organotypic epithelium at a 50-fold lower concentration than UAB30. This was consistent with the 2- to 5- fold greater increase in ATRA in organotypic epidermis treated with UAB110/111 versus UAB30. Furthermore, at 0.2 μM, UAB110/111 increased the expression of ATRA genes up to 16-fold stronger than Targretin. The less toxic and more potent UAB110 also induced more changes in differential gene expression than Targretin. Additionally, our hydrogen deuterium exchange mass spectrometry analysis showed that both ligands reduced the dynamics of the ligand-binding pocket but also induced unique dynamic responses that were indicative of higher affinity binding relative to UAB30, especially for Helix 3. UAB110 binding also showed increased dynamics towards the dimer interface through the Helix 8 and Helix 9 regions. These data suggest that UAB110 and UAB111 are potent activators of RXR-RAR signaling pathways but accomplish activation through different molecular responses to ligand binding.

01 Jan 2021·Translational Oncology

9-cis-UAB30, a novel rexinoid agonist, decreases tumorigenicity and cancer cell stemness of human neuroblastoma patient-derived xenografts

Article

Author: Stafman, Laura L ; Yoon, Karina J ; Marayati, Raoud ; Bownes, Laura V ; Aye, Jamie M ; Stewart, Jerry E ; Williams, Adele P ; Quinn, Colin H ; Beierle, Elizabeth A ; Atigadda, Venkatram

Retinoic acid (RA) therapy has been utilized as maintenance therapy for high-risk neuroblastoma, but over half of patients treated with RA relapse. Neuroblastoma stem cell-like cancer cells (SCLCCs) are a subpopulation of cells characterized by the expression of the cell surface marker CD133 and are hypothesized to contribute to drug resistance and disease relapse. A novel rexinoid compound, 9-cis-UAB30 (UAB30), was developed having the same anti-tumor effects as RA but a more favorable toxicity profile. In the current study, we investigated the efficacy of UAB30 in neuroblastoma patient-derived xenografts (PDX). Two PDXs, COA3 and COA6, were utilized and alterations in the malignant phenotype were assessed following treatment with RA or UAB30. UAB30 significantly decreased proliferation, viability, and motility of both PDXs. UAB30 induced cell-cycle arrest as demonstrated by the significant increase in percentage of cells in G1 (COA6: 33.7 ± 0.7 vs. 43.3 ± 0.7%, control vs. UAB30) and decrease in percentage of cells in S phase (COA6: 44.7 ± 1.2 vs. 38.6 ± 1%, control vs. UAB30). UAB30 led to differentiation of PDX cells, as evidenced by the increase in neurite outgrowth and mRNA abundance of differentiation markers. CD133 expression was decreased by 40% in COA6 cells after UAB30. The ability to form tumorspheres and mRNA abundance of known stemness markers were also significantly decreased following treatment with UAB30, further indicating decreased cancer cell stemness. These results provide evidence that UAB30 decreased tumorigenicity and cancer cell stemness in neuroblastoma PDXs, warranting further exploration as therapy for high-risk neuroblastoma.

01 Jan 2021·Translational OncologyQ3 · MEDICINE

Rewiring Tumor Cell State in Cancer Therapy: Comment on ‘9-cis-UAB30, a Novel Rexinoid Agonist, Decreases Tumorigenicity and Cancer Cell Stemness of Human Neuroblastoma Patient-Derived Xenografts’ by ‘Elizabeth Beierle et al.’

Q3 · MEDICINE

ArticleOA

Author: Chakraborty, Abhishek A

100 Deals associated with (9Z)-UAB-30

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB12316

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Skin Neoplasms	Phase 2	US	The University of Alabama at Birmingham	01 Oct 2020
Early Stage Breast Carcinoma	Phase 1	US	National Cancer Institute	16 Mar 2018
Invasive Mammary Carcinoma	Phase 1	US	National Cancer Institute	16 Mar 2018
Noninfiltrating Intraductal Carcinoma	Phase 1	US	National Cancer Institute	16 Mar 2018
Neoplasms	Phase 1	-	The University of Alabama at Birmingham	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


SABCS2022	Not Applicable	BRCA mutation positive Breast Cancer Brca1 mutant	-	Sesame oil control	(gwuzucewyc) = a significant increase in lipid accumulation accompanied by a 2-fold increase of Srebf1 expression (a key transcription factor that regulates lipid homeostasis) within 24 hours of treatment (p< 0.05) pfelegsdei (oajqsyqiiy )	-	15 Mar 2022
				IRX-4204 10mg/kg
SABCS2021	Not Applicable	BRCA mutation positive Breast Cancer BRCA1 mutations	-	Sesame oil control	(mtsggozjjz) = apojxapbfj rxnesbzdel (tksfqzstpb )	Positive	15 Oct 2021
				IRX-4204 10mg/kg	(mtsggozjjz) = sgbviuhrqu rxnesbzdel (tksfqzstpb )
SABCS2023	Not Applicable	BRCA mutation positive Breast Cancer Brca1 mutant	-	Sesame oil control	vdzpnaibed(yyqfjmacpr) = a significant increase in lipid accumulation accompanied by a 2-fold increase of Srebf1 expression (a key transcription factor that regulates lipid homeostasis) within 24 hours of treatment (p< 0.05) vhwxetmhpq (ukjrxmhquv )	-	05 Dec 2023
				IRX-4204 10mg/kg