Delving into the Latest Updates on Phenoxodiol with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

3-(4-hydroxyphenyl)-2H-chromen-7-ol, Dehydroequol, Haginin E

+ [4]

Target

S1PRs x SPHK1 x SPHK2

Mechanism

S1PRs antagonists(Sphingosine 1-phosphate receptor antagonists), SPHK2 inhibitors(Sphingosine kinase 2 inhibitors), SPK 1 inhibitors(Sphingosine kinase 1 inhibitors)

Therapeutic Areas

Infectious DiseasesOther Diseases

Active Indication

Sepsis

Inactive Indication

Breast CancerCastration-Resistant Prostatic CancerCOVID-19+ [11]

Originator Organization

MEI Pharma, Inc.

Active Organization

Noxopharm Ltd.

Inactive Organization

MEI Pharma, Inc.

Royal North Shore Hospital

Kazia Therapeutics Ltd.

Drug Highest PhasePreclinical

First Approval Date-

RegulationOrphan Drug (US), Orphan Drug (EU)

Structure

Molecular FormulaC15H12O3

InChIKeyZZUBHVMHNVYXRR-UHFFFAOYSA-N

CAS Registry81267-65-4

This is a Phase I, open-label, dose-escalation and dose-expansion study of NOX66 given rectally, in cohorts of patients with metastatic soft tissue sarcoma (STS) who have not been exposed to anthracycline therapy, using a fixed dose-escalation schema every 21 days to establish the maximum tolerated dose (MTD) of the combination of NOX66 and doxorubicin.

Start Date11 Feb 2022

Sponsor / Collaborator

Noxopharm Ltd.

EUCTR2021-001917-35-HU / Unknown statusPhase 1/2

A Phase 1b/2a Multicenter Study of NOX66 and External Beam Radiotherapy in Patients with Metastatic Castration-resistant Prostate Cancer and Other Solid Tumors

Start Date25 Oct 2021

Sponsor / Collaborator

Noxopharm Ltd.

NCT04957290 / TerminatedPhase 1/2

A Phase 1b/2a Multicenter Study of NOX66 and External Beam Radiotherapy in Patients With Metastatic Castration-resistant Prostate Cancer and Other Solid Tumors

This is a Phase 1b/Phase 2a, open-label, multicenter study to determine the safety, tolerability, recommended Phase 2 dose (RP2D), efficacy, pharmacokinetics (PK) and pharmacodynamic (PD) properties of idronoxil when rectally administered as a suppository (NOX66) to patients with any solid tumor (Part 1) and patients with metastatic castration-resistant prostate cancer (mCRPC), breast cancer (BC) and non-small-cell lung cancer (NSCLC) (Part 2) who are eligible for low-dose external beam radiotherapy (EBRT) for at least one symptomatic or minimally symptomatic lesion (for the prevention of symptoms).

Start Date25 Oct 2021

Sponsor / Collaborator

Noxopharm Ltd.

100 Clinical Results associated with Phenoxodiol

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100 Translational Medicine associated with Phenoxodiol

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100 Patents (Medical) associated with Phenoxodiol

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96

Literatures (Medical) associated with Phenoxodiol

01 Feb 2024·Journal of advanced research

ENOX2 inhibition enhances infiltration of effector memory T-cell and mediates response to chemotherapy in immune-quiescent nasopharyngeal carcinoma

Article

Author: Kam, Ngar-Woon ; Li, Xiang ; Dai, Wei ; Wu, Ka Chun ; Lee, Victor Ho-Fun ; Kwong, Dora Lai-Wan ; Hung, Desmond ; Laczka, Olivier ; Che, Chi Ming ; Tsao, Sai Wa ; Lai, Syrus Pak Hei ; Wilkinson, John

INTRODUCTION:

The immunosuppressive tumor microenvironment is a major barrier for chemotherapy. Different chemosensitization approaches to reinstate immunological surveillance for cancers that are immune quiescent at the outset, have thus been devised. Cancer-specific ENOX2 expression is correlated with abnormal cell growth and has been proposed as a cellular target for anti-cancer activity. However, the potential effects of ENOX2 on the interaction between immune system and tumor cells remain elusive.

OBJECTIVES:

To understand the mechanisms by which tumor-intrinsic ENOX2-mediated alterations in anti-tumor activity of T-cells and response to chemotherapy.

METHODS:

In situ multiplexed immunohistochemistry with single cell and bulk RNA sequencing data from nasopharyngeal carcinoma (NPC) human tissues were used to define tumor phenotypes. Two NPC cell lines, with distinct ENOX2 expression, were used in a co-culture platform to study tumor-immune interactions between cancer cells/spheroids and T-cells. The effect of cisplatin treatment with ENOX2 inhibition by idronoxil (IDX) were tested in vitro and in vivo. Multi-parametric flow cytometry was used to characterize T-cell infiltrates in an NPC tumor humanized mouse model treated with combined treatment.

RESULTS:

NPC predominantly displayed an immune-excluded profile. This "cold-phenotype" was shown to exhibit higher ENOX2 expression and was associate with poorer progression-free survival (PFS). The therapeutic combination of IDX with cisplatin was effective in promoting CD8⁺ effector memory T cell (Tem) differentiation and mobilization. This Tem signature was highly cytotoxic, with Tem-mediated preferential lysis of higher ENOX2-expressing NPC cells. A combination-treated humanized mouse model showing dramatic shrinkage in tumors, were intra-tumoral Tem-enriched.

CONCLUSION:

Tumor-intrinsic ENOX2 expression is associated with tumor phenotype and PFS in NPC. Targeting ENOX2 with IDX and cisplatin impose qualitative control of T-cell response by preferentially increasing immune cells infiltration, Tem differentiation and tumor suppression. We suggest that ENOX2 inhibition may be a promising therapeutic strategy to enhance the effects of chemotherapy.

03 Oct 2023·Recent patents on anti-cancer drug discovery

Characterization of the Prognosis and Tumor Microenvironment of Cellular Senescence-related Genes through scRNA-Seq and Bulk RNA-Seq Analysis in GC.

Article

Author: Ye, Yunbin ; Wang, Yang ; Lan, Tianshu ; Chen, Shuping ; Cheng, Jiaqing ; Zhou, Zhifeng ; Guo, Guoxiang

BACKGROUND:

Cellular senescence (CS) is thought to be the primary cause of cancer development and progression. This study aimed to investigate the prognostic role and molecular subtypes of CS-associated genes in gastric cancer (GC).

METHODS:

The CellAge database was utilized to acquire CS-related genes. Expression data and clinical information of GC patients were obtained from The Cancer Genome Atlas (TCGA) database. Patients were then grouped into distinct subtypes using the "ConsesusClusterPlus" R package based on CS-related genes. An in-depth analysis was conducted to assess the gene expression, molecular function, prognosis, gene mutation, immune infiltration, and drug resistance of each subtype. In addition, a CS-associated risk model was developed based on Cox regression analysis. The nomogram, constructed on the basis of the risk score and clinical factors, was formulated to improve the clinical application of GC patients. Finally, several candidate drugs were screened based on the Cancer Therapeutics Response Portal (CTRP) and PRISM Repurposing dataset.

RESULTS:

According to the cluster result, patients were categorized into two molecular subtypes (C1 and C2). The two subtypes revealed distinct expression levels, overall survival (OS) and clinical presentations, mutation profiles, tumor microenvironment (TME), and drug resistance. A risk model was developed by selecting eight genes from the differential expression genes (DEGs) between two molecular subtypes. Patients with GC were categorized into two risk groups, with the high-risk group exhibiting a poor prognosis, a higher TME level, and increased expression of immune checkpoints. Function enrichment results suggested that genes were enriched in DNA repaired pathway in the low-risk group. Moreover, the Tumor Immune Dysfunction and Exclusion (TIDE) analysis indicated that immunotherapy is likely to be more beneficial for patients in the low-risk group. Drug analysis results revealed that several drugs, including ML210, ML162, dasatinib, idronoxil, and temsirolimus, may contribute to the treatment of GC patients in the high-risk group. Moreover, the risk model genes presented a distinct expression in single-cell levels in the GSE150290 dataset.

CONCLUSION:

The two molecular subtypes, with their own individual OS rate, expression patterns, and immune infiltration, lay the foundation for further exploration into the GC molecular mechanism. The eight gene signatures could effectively predict the GC prognosis and can serve as reliable markers for GC patients.

01 Mar 2023·Acta pharmacologica Sinica

SZC-6, a small-molecule activator of SIRT3, attenuates cardiac hypertrophy in mice

Article

Author: Lu, Guo-Qing ; Lu, Jing ; Wang, Pan-Xia ; Li, Ze-Yu ; Liu, Pei-Qing ; Zou, Yong ; Zhang, Xiao-Lei

Sirtuin3 (SIRT3), a class III histone deacetylase, is implicated in various cardiovascular diseases as a novel therapeutic target. SIRT3 has been proven to be cardioprotective in a model of Ang II-induced cardiac hypertrophy. However, a few small-molecule compounds targeting deacetylases could activate SIRT3. In this study, we generated a novel SIRT3 activator, 3-(2-bromo-4-hydroxyphenyl)-7-hydroxy-2H-chromen-2-one (SZC-6), through structural optimization of the first SIRT3 agonist C12. We demonstrated that SZC-6 directly bound to SIRT3 with K_d value of 15 μM, and increased SIRT3 deacetylation activity with EC₅₀ value of 23.2 ± 3.3 µM. In neonatal rat cardiomyocytes (NRCMs), pretreatment with SZC-6 (10, 20, 40 µM) dose-dependently attenuated isoproterenol (ISO)-induced hypertrophic responses. Administration of SZC-6 (20, 40 and 60 mg·kg^-1·d^-1_, s.c.) for 2 weeks starting from one week prior ISO treatment dose-dependently reversed ISO-induced impairment of diastolic and systolic cardiac function in wild-type mice, but not in SIRT3 knockdown mice. We showed that SZC-6 (10, 20, 40 µM) dose-dependently inhibited cardiac fibroblast proliferation and differentiation into myofibroblasts, which was abolished in SIRT3-knockdown mice. We further revealed that activation of SIRT3 by SZC-6 increased ATP production and rate of mitochondrial oxygen consumption, and reduced ROS, improving mitochondrial function in ISO-treated NRCMs. We also found that SZC-6 dose-dependently enhanced LKB1 phosphorylation, thereby promoting AMPK activation to inhibit Drp1-dependent mitochondrial fragmentation. Taken together, these results demonstrate that SZC-6 is a novel SIRT3 agonist with potential value in the treatment of cardiac hypertrophy partly through activation of the LKB1-AMPK pathway.

2

News (Medical) associated with Phenoxodiol

11 Feb 2021

·www.biospace.com

Noxopharm Shares Major Cancer Survival Benefit at ASCO Global Conference

SYDNEY--(BUSINESS WIRE)-- Australian clinical-stage drug development company, Noxopharm, is pleased to report the publication of the latest survival data from the LuPIN study ahead of their formal presentation to the American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium (February 11-13, 2021), the preeminent medical conference dedicated to sharing the most recent innovations in the treatment of genitourinary cancers. The results showed a median overall survival (mOS) of 19.7 months, exceeding all other mOS results for existing prostate cancer treatments in their own registration studies. This supports evidence that a combination of Veyonda® (NOX66) and the experimental radiopharmaceutical, 177lutetium-PSMA-617, is a long-awaited leap forward in the treatment of metastatic castrate-resistant prostate cancer (mCRPC). This offers a patient with mCRPC a high chance of the cancer responding to treatment to the extent of obtaining a meaningful survival outcome. “This clinical data continues to cement the view that Veyonda is on track to become a major new immunotherapy oncology drug of medical and commercial significance,” said Noxopharm CEO Dr. Graham Kelly. “The investigators chose to test the LuPIN combination in men with end-stage disease as being the most stringent test possible. Providing men at this stage with an opportunity to achieve about an average of 20 months of life, with obviously more in some men, is an extraordinary outcome. This could potentially revolutionize the treatment of end-stage prostate cancer.” The study enrolled a total of 56 patients whose cancers had progressed to an advanced stage despite standard therapy. The goal of the combined treatment was to slow or block tumor progression to deliver better quality of life and extended survival for these men, and to do so in a well-tolerated way. Noxopharm sees the next step as taking the combination further upstream in the treatment process with a view to it becoming an early standard-of-care treatment. About Noxopharm Noxopharm is a clinical-stage Australian oncology drug development company with offices in Sydney and New York. The company has a primary focus on the development of Veyonda® and is the major shareholder in the nononcology drug development company, Nyrada Inc.

ImmunotherapyASCO

22 Sep 2009

·www.biospace.com

Marshall Edwards, Inc. Receives Nasdaq Notice of Minimum Bid Price Non-Compliance

NEW CANAAN, CT--(Marketwire - September 22, 2009) - Marshall Edwards, Inc. (NASDAQ: MSHL), a specialist oncology company focusing on the clinical development of novel anti-cancer therapeutics, today announced that on September 16, 2009, as management expected, the Company received a letter from The Nasdaq Stock Market notifying the Company that for the last 30 consecutive business days the bid price of the Company's common stock closed below the minimum $1.00 per share requirement for continued inclusion on the Nasdaq Global Market under Nasdaq Rule 5450(a)(1). According to Nasdaq's letter, the Company will be afforded a grace period of 180 calendar days, or until March 15, 2010, to regain compliance in accordance with Nasdaq Rule 5810(c)(3)(A). In order to regain compliance, shares of the Company's common stock must maintain a minimum bid closing price of at least $1.00 per share for a minimum of ten consecutive business days during the grace period. The Company intends to actively monitor the bid price of its common stock between now and March 15, 2010. About Marshall Edwards, Inc. Marshall Edwards, Inc. is a specialist oncology company focused on the clinical development of novel anti-cancer therapeutics. These derive from a flavonoid technology platform, which has generated a number of novel compounds characterized by broad ranging activity against a range of cancer cell types with few side effects. The combination of anti-tumor cell activity and low toxicity is believed to be a result of the ability of these compounds to target an enzyme present in the cell membrane of cancer cells, thereby inhibiting the production of pro-survival proteins within the cell. Marshall Edwards has licensed rights from Novogen Limited (ASX: NRT) (NASDAQ: NVGN) to bring four oncology drugs -- phenoxodiol, triphendiol NV-143 and NV-128 -- to market globally. Marshall Edwards is majority owned by Novogen, an Australian biotechnology company that is specializing in the development of therapeutics based on a flavonoid technology platform. Novogen is developing a range of therapeutics across the fields of oncology, cardiovascular disease and inflammatory diseases. More information on phenoxodiol and on the Novogen group of companies can be found at and . Under U.S. law, a new drug cannot be marketed until it has been investigated in clinical trials and approved by the FDA as being safe and effective for the intended use. Statements included in this press release that are not historical in nature are "forward-looking statements" within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. You should be aware that our actual results could differ materially from those contained in the forward-looking statements, which are based on management's current expectations and are subject to a number of risks and uncertainties, including, but not limited to, our failure to successfully commercialize our product candidates; costs and delays in the development and/or FDA approval, or the failure to obtain such approval, of our product candidates; uncertainties in clinical trial results; our inability to maintain or enter into, and the risks resulting from our dependence upon, collaboration or contractual arrangements necessary for the development, manufacture, commercialization, marketing, sales and distribution of any products; competitive factors; our inability to protect our patents or proprietary rights and obtain necessary rights to third party patents and intellectual property to operate our business; our inability to operate our business without infringing the patents and proprietary rights of others; general economic conditions; the failure of any products to gain market acceptance; our inability to obtain any additional required financing; technological changes; government regulation; changes in industry practice; and one-time events. We do not intend to update any of these factors or to publicly announce the results of any revisions to these forward-looking statements. CONTACTS: Warren Lancaster +1-203-966-2556 (USA) Email Contact David Sheon +1 202 547-2880 (USA) Email Contact

100 Deals associated with Phenoxodiol

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External Link

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Fallopian Tube Carcinoma	Phase 3	US	MEI Pharma, Inc.	01 Oct 2006
Fallopian Tube Carcinoma	Phase 3	AU	MEI Pharma, Inc.	01 Oct 2006
Fallopian Tube Carcinoma	Phase 3	BE	MEI Pharma, Inc.	01 Oct 2006
Fallopian Tube Carcinoma	Phase 3	IT	MEI Pharma, Inc.	01 Oct 2006
Fallopian Tube Carcinoma	Phase 3	PL	MEI Pharma, Inc.	01 Oct 2006
Fallopian Tube Carcinoma	Phase 3	ES	MEI Pharma, Inc.	01 Oct 2006
Fallopian Tube Carcinoma	Phase 3	GB	MEI Pharma, Inc.	01 Oct 2006
Platinum-Resistant Primary Peritoneal Carcinoma	Phase 3	US	MEI Pharma, Inc.	01 Oct 2006
Platinum-Resistant Primary Peritoneal Carcinoma	Phase 3	AU	MEI Pharma, Inc.	01 Oct 2006
Platinum-Resistant Primary Peritoneal Carcinoma	Phase 3	BE	MEI Pharma, Inc.	01 Oct 2006

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04957290 (CTgov)	Phase 1/2	Metastatic castration-resistant prostate cancer	21	EBRT+NOX66 (Part 1: Dose Cohort 1: NOX66 800 mg)	ffnfyzcfiy(hfxdckyslu) = qhjqkkdrbn ckeqguzwmb (azelxzqidy, vvplzxpbji - wrbeyhcpkg) View more	-	18 Jun 2024
NCT04957290 (CTgov)	Phase 1/2	Metastatic castration-resistant prostate cancer	21	EBRT+NOX66 (Part 1: Dose Cohort 2: NOX66 1200 mg)	ffnfyzcfiy(hfxdckyslu) = mlxkvdkgqu ckeqguzwmb (azelxzqidy, mhwebiwkqq - estuwaevfj) View more	-	18 Jun 2024
ACTRN12621001537842 (IONIC-1, ASCO2023) Manual	Phase 1/2	Advanced cancer	11	nivolumab+NOX66	rtiavikhkw(hqsuaatqli) = The most common AE was local perineal irritation, readily managed with topical corticosteroid cream. plxbxdsqaw (zatcdixbar )	Positive	31 May 2023
NCT03307629 (ASCO2020)	Phase 1	Metastatic castration-resistant prostate cancer	25	NOX66 + radiation therapy	ilgonnhdmq(zumyobswza) = TEAEs considered related to NOX66 alone were mild (Grade 1) cases of dry mouth and oral mucositis; mild (Grade 1) fatigue was considered related to both NOX66 and radiation. None of the 21 Grade ≥3 TEAEs were considered related to NOX66 dpihjxzzmf (kjfhiethke )	Positive	25 May 2020
NCT03307629 (GlobeNewswire) Manual	Phase 1	Prostatic Cancer	25	palliative radiotherapy+Veyonda	tkgkdkqwpu(eygwgbtxvh) = zejbsykedd pmsofvqkcn (pzreqnhzic ) View more	Positive	02 Dec 2019
AUA2017	Not Applicable	Kidney Neoplasms	-	Phenoxodiol	fpcjrllhbl(lzycphcjqc) = Phenoxodiol also inhibited the Akt pathway by causing dephosphorylation of Akt. This inhibition of the Akt pathway inhibited expression of the apoptosis inhibitor FLIP and thus led to renal cancer apoptosis bmbtwoxahf (ohmmiyzfuu ) View more	-	01 Apr 2017
NCT00382811 (OVATURE, Pubmed \| Ann Oncol)	Phase 3	Platinum-Resistant Ovarian Carcinoma	142	Phenoxodiol + AUC2-carboplatin	yilvixciod(hmwijachkv) = gxlrxymeok anliojqlmd (wescsztwdf, 11.1 - 21.0) View more	Negative	01 Jan 2014
NCT00382811 (OVATURE, Pubmed \| Ann Oncol)	Phase 3	Platinum-Resistant Ovarian Carcinoma	142	Placebo + AUC2-carboplatin	yilvixciod(hmwijachkv) = ejvbnefhjo anliojqlmd (wescsztwdf, 13.1 - 33.4) View more	Negative	01 Jan 2014
NCT00091377 (Pubmed \| Int J Gynecol Cancer)	Phase 2	Platinum-Resistant Primary Peritoneal Carcinoma	65	Cisplatin + Phenoxodiol	lrmqlyqkbp(avmrsqjgyw) = ocijpsnlgn fszuyarvfa (bgzewlggmj )	-	01 May 2011
NCT00091377 (Pubmed \| Int J Gynecol Cancer)	Phase 2	Platinum-Resistant Primary Peritoneal Carcinoma	65	Paclitaxel + Phenoxodiol	lrmqlyqkbp(avmrsqjgyw) = fxpvmgjwxb fszuyarvfa (bgzewlggmj )	-	01 May 2011
ASCO2010	Phase 2	Castration-Resistant Prostatic Cancer	-	oral phenoxodiol (Castrate-resistant prostate cancer patients)	sfywtgilfh(eeeuqfusql) = frjopenvkj jzsrltkjbi (lgehmxhnbf )	-	20 May 2010