Delving into the Latest Updates on Sulforadex with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

(-)-sulforaphane, (R)-sulforaphane, 4-methylsulfinylbutyl isothiocyanate

+ [8]

Target

HDACs

Mechanism

HDAC inhibitors(Histone deacetylase inhibitors)

Therapeutic Areas

NeoplasmsNervous System DiseasesOther Diseases

Active Indication

GlioblastomaNeurodevelopmental DisordersAutism Spectrum Disorder+ [1]

Inactive Indication

Acute Myeloid LeukemiaAutistic DisorderBreast Cancer+ [13]

Originator Organization

PharmAgra Labs, Inc.

Active Organization

Stalicla SAStartup

TheraCryf Plc

Inactive Organization-

Drug Highest PhasePhase 1

First Approval Date-

RegulationOrphan Drug (US)

Structure

Molecular FormulaC6H11NOS2

InChIKeySUVMJBTUFCVSAD-UHFFFAOYSA-N

CAS Registry4478-93-7

BACKGROUNDThe presence of distant metastasis at the time of initial diagnosis is a prevalent issue in non-small cell lung cancer (NSCLC), affecting around 30-40 % of the patients. Acidic tumor microenvironment (TME) provides favorable conditions that increase the invasiveness and aggressiveness of NSCLC. The activity of the glycolytic enzyme lactate dehydrogenase (LDHA) increases intracellular lactate accumulation, which creates an acidic TME. However, it is not yet known whether LDHA is involved in enhancing the metastatic potential of NSCLC and if LDHA is a druggable therapeutic target for NSCLC.PURPOSEWe aimed to investigate the molecular mechanisms underlying the enhanced NSCLC metastasis in acidic TME, and to explore whether sulforaphane (SFN), an active compound in Raphani Semen, can serve as a LDHA inhibitor to inhibit NSCLC metastasis in the acidic TME.METHODSTo mimic the acidic TME, NSCLC cells were cultured in acidic medium (pH 6.6), normal medium (pH 7.4) served as control. Western blotting, bioinformatic analysis, luciferase assay and rescue experiments were used to explore the mechanism and investigate the anti-metastatic effect of SFN both in vitro and in vivo.RESULTSAcidic environment increases the expression of LDHA which in turn increases the production of lactic acid that contributes to the acidity of TME. Interestingly, elevated LDHA expression results from increased c-Myc expression, which transactivates LDHA. c-Myc expression is directly regulated by miR-7-5p. In vitro study shows that overexpression of miR-7-5p reverses the acidic pH-enhanced c-Myc and LDHA expressions and also abolishes the enhanced NSCLC cell migration. More importantly, SFN significantly inhibits NSCLC growth and metastasis by reducing lactate production via the miR-7-5p/c-Myc/LDHA axis. Besides, it also regulates the expressions of monocarboxylate transporter 1 (MCT1) and MCT4 that transport lactate across cell membrane.CONCLUSIONSThe miR-7-5p/c-Myc/LDHA axis is involved in the enhanced NSCLC metastasis in the acidic TME. SFN, a novel LDHA inhibitor, reduces lactate production by targeting the miR-7-5p/c-Myc/LDHA axis, and hence inhibits NSCLC metastasis. Our findings not only delineate a novel mechanism, but also support the clinical translation of SFN as a novel therapeutic agent for treating metastatic NSCLC.

01 Oct 2024·International Immunopharmacology

Combined sulforaphane and β-sitosterol mitigate olanzapine-induced metabolic disorders in rats: Insights on FOXO, PI3K/AKT, JAK/STAT3, and MAPK signaling pathways

Article

Author: Salem, Esraa A ; Farghaly, Omar A ; Saad, Hebatallah M ; Atwa, Ahmed M ; Abdelzaher, Lobna A ; Mahmoud, Nesreen I ; Elhussieny, Omnya ; Girgis Shahataa, Mary ; Sabry, Mostafa ; Kozman, Magy R ; El-Shoura, Ehab A M

One of the best antipsychotics for treating schizophrenia and bipolar disorders is olanzapine (OLA). However, its use is restricted owing to unfavorable adverse effects as liver damage, dyslipidemia, and weight gain. The primary objective of the present investigation was to examine the signaling mechanisms that underlie the metabolic disruption generated by OLA. Besides, the potential protective effect of sulforaphane (SFN) and β-sitosterol (βSS) against obesity and metabolic toxicity induced by OLA were inspected as well. A total of five groups of male Wistar rats were established, including the control, OLA, SFN+OLA, βSS+OLA, and the combination + OLA groups. Hepatic histopathology, biochemical analyses, ultimate body weights, liver function, oxidative stress, and pro-inflammatory cytokines were evaluated. In addition to the relative expression of FOXO, the signaling pathways for PI3K/AKT, JAK/STAT3, and MAPK were assessed as well. All biochemical and hepatic histopathological abnormalities caused by OLA were alleviated by SFN and/or βSS. A substantial decrease in systolic blood pressure (SBP), proinflammatory cytokines, serum lipid profile parameters, hepatic MDA, TBIL, AST, and ALT were reduced through SFN or/and βSS. To sum up, the detrimental effects of OLA are mediated by alterations in the Akt/FOXO3a/ATG12, Ras/SOS2/Raf-1/MEK/ERK1/2, and Smad3,4/TGF-β signaling pathways. The administration of SFN and/or βSS has the potential to mitigate the metabolic deficit, biochemical imbalances, hepatic histological abnormalities, and the overall unfavorable consequences induced by OLA by modulating the abovementioned signaling pathways.

01 Sep 2024·Biochemical and Biophysical Research Communications

Inhibition of soluble epoxide hydrolase by natural isothiocyanates

Article

Author: Yee, Baily ; Elbarbry, Fawzy ; Espiritu, Michael J ; Taylor, Jonathan ; Soo, Kaylen

GOALThe long-term goal of our research is to develop safe and effective soluble epoxide hydrolase (sEH) inhibitors. The objective of this study is to evaluate the potency and selectivity of six natural isothiocyanates (ITCs) as sEH inhibitors.METHODSMolecular docking was used to model likely interactions between the ligands and receptors. The sEH inhibitory activity was tested using a validated fluorescence-based assay and PHOME as a substrate. To evaluate their selectivity as sEH inhibitors, the inhibitory potential of the ITCs was determined on microsomal epoxide hydrolase (mEH) and cytochrome P450 (CYP) enzymes in human liver microsomes. Probe substrates such as styrene oxide (mEH substrate) and established substrates for CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4 were used in this study. The metabolites of these substrates were analyzed using validated LC-MS/MS and HPLC-UV assays.RESULTSMolecular Docking revealed significant differences in binding site preference among the ITCs in silico and pointed to important interactions between the ligands and the catalytic residues of the sEH enzyme. In vitro, the ITCs showed varying degrees of sEH inhibition, but sulforaphane (SFN) and phenyl isothiocyanate (PITC) were the most potent inhibitors with IC₅₀ values of 3.65 and 7.5 μM, respectively. mEH was not significantly inhibited by any of the ITCs. Erucin and iberin were the only ITCs that did not inhibit the activity of any of the tested CYP enzymes.CONCLUSIONOur results demonstrate that natural ITCs have the potential to offer safe, selective, and potent sEH inhibition.

17

News (Medical) associated with Sulforadex

04 Mar 2024

·www.biospace.com

Therapeutic Solutions International Granted Patent on Commercially Available QuadraMune® Nutraceutical for Increasing Natural Killer Cell Immunity in COVID-19 Patients

Latest Patent to Complement Issued Claims on Viral Inhibition, Adaptive Immune Stimulation, and Brain Protection/Regeneration ELK CITY, Idaho--(BUSINESS WIRE)-- Therapeutic Solutions International, Inc. (TSOI), a clinical-stage stem cell and immunotherapy company, announced today the granting of a patent covering the ability of QuadraMune® and similar compositions, to stimulate natural killer (NK) cell activity in patients with COVID-19. NK cells are the first line of defense against viruses and cancers1. The Company was previously awarded by the United States Patent and Trademark Office the following QuadraMune® related patents: Patent #11,229,674, covering inhibition of the immune suppressing enzyme indolamine 2,3 dioxygenase2. It is published that this enzyme plays a fundamental role in immune suppression by cancer3, as well as numerous viruses including SARS-CoV-2, the causative agent of COVID-194. Patent #11,266,707, “Nutraceuticals for the prevention, inhibition, and treatment of SARS-CoV-2 and associated COVID-19”5. Patent #11,504,410, covering use of QuadraMune® and its derivatives for protecting and restoring brain function after neurological damage, including Long COVID6. Patent #11759495, covering upregulation of T regulatory cells for suppression of suicidal ideation7. “In addition to this important validation from the USPTO, the fact that the ingredients in QuadraMune® have been reported by institutions such as Johns Hopkins University to suppress SARS-CoV-2 is strongly encouraging,” said Famela Ramos, Vice President of Business Development for the Company. “Our Company is driven by a desire to address unmet medical needs, whether it is through developing state of the art stem cell and gene therapies, or science-backed nutraceuticals,” said Timothy Dixon, President, and CEO of the Company. “The importance of NK cells in protecting the body against cancer and viruses is well known, the fact that this can be performed using a low-cost nutraceutical approach has implications in both oncology and virology.” About Therapeutic Solutions International, Inc. Therapeutic Solutions International is focused on immune modulation for the treatment of several specific diseases. The Company's corporate website is . 1 Cerwenka and Lanier. Natural killer cells, viruses and cancer. Nat Rev Immunol. 2001 Oct;1(1):41-9. 2 3 Ricuitti et al. Targeting indoleamine-2,3-dioxygenase in cancer: Scientific rationale and clinical evidence. Pharmacol Ther. 2019 Apr:196:105-116. 4 Guo et al. Indoleamine 2,3-dioxygenase (IDO)-1 and IDO-2 activity and severe course of COVID-19. J Pathol. 2022 Mar;256(3):256-261. 5 6 7 8 Johns Hopkins University Publishes Efficacy of QuadraMune™ Ingredient Sulforaphane at Inhibiting Coronavirus in Laboratory Studies | BioSpace

Immunotherapy

17 Jan 2024

·www.pharmaceutical-technology.com

Stalica raises $17.5m to advance neurology programmes

The ASD pipeline consists of 127 drugs spanning all stages of development, with only 7% of drugs present in Phase III and 11.8% in Phase II clinical development. Image Credit: Alex and Maria photo / Shutterstock. Switzerland-based Stalica has raised $17.5m in Series B financing to fund clinical trials for its neuropsychiatric and neurological disorders pipeline. The clinical programmes that the company plans to use the Series B proceeds include the fixed-dose combination drug STP1 and mavoglurant (STP7). Furthermore, the company will also strengthen the data package for STP2. Stalica’s clinical pipeline STP1 is a fixed dose combination of ibudilast, a phosphodiesterase (PDE) 4/3 inhibitor, and bumetanide, a sodium (Na)- potassium (K)- chloride (Cl) cotransporter (NKCC) 1 agonist. Stalica is developing the precision therapy as a treatment for autism spectrum disorder (ASD) in a specific sub-group of patients, phenotype 1 (Phen1). Phen1 patients have been identified by Stalica and validated using two independent clinical observational/bio-sampling studies (NCT05590715 and NCT04644003). The company is planning a Phase II trial for STP1 in patients with ASD, the preparation of which will be funded by the proceeds from the current financing round. Mavoglurant is a negative allosteric modulator of the glutamate receptor 5 (mGluR5). Stalica signed an in-licencing agreement with Novartis to develop the drug as a treatment for substance-use disorders and neurodevelopmental disorders (NDDs) in January 2023. As per the agreement, the company is entitled to receive up to $270m in upfront and milestone-based payments along with royalties on net sales. The company is planning a Phase III trial for mavoglurant in patients with cocaine use disorder in 2025. The trial will be funded by the US National Institute on Drug Abuse (NIDA), part of the US National Institutes of Health (NIH). It is expected to enrol up to 330 patients. STP2 is a stabilised synthetic form of sulforaphane. Stalica acquired the rights to the therapy from the UK-based Evgen Pharma in October 2022. Stalica is developing STP2 as a treatment for ASD in Phen2 sub-population. The company plans to start Phase II trial for the therapy in 2023. ASD landscape The total diagnosed prevalence of ASD was more than 9.81 million in 2023 and is expected to be approximately 9.65 million diagnosed prevalent cases of ASD in 2028, as per a 2023 Globaldata report . The ASD pipeline consists of 127 drugs spanning all stages of development, with only 7% of drugs present in Phase III and 11.8% in Phase II clinical development. GlobalData is the parent company of Pharmaceutical Technology . In November 2023, SciSparc started a clinical trial for SCI-210 to treat ASD symptoms in children. SCI-210 is a combination of cannabidiol (CBD) and palmitoylethanolamide. The trial is expected to enrol 60 patients aged five and 18 years. Apart from ASD treatment, strides have been made in developing diagnostics for the disorder. In September 2023, EarliTech positive data from two studies showing the efficacy and accuracy of its EarliPoint Evaluation device in diagnosing and assessing autism in children aged 30 months and older.

Phase 2Phase 3

05 Dec 2023

·www.globenewswire.com

Bon Natural Life Limited Announces $45 Million Broccoli Product Order with Beijing Huahai Keyuan

XI’AN, China, Dec. 05, 2023 (GLOBE NEWSWIRE) -- Bon Natural Life Limited (Nasdaq: BON) ("BON" or the "Company"), one of the leading bio-ingredient solutions providers in the natural, health and personal care industries, today announced that it has entered into a sales distributing contract with Beijing Huahai Keyuan Technology Co. Ltd. (“Huahai”). The contract grants Huahai the priority rights to sell BON’s broccoli products in the Chinese market with a total product value of US$45 million. BON’s most recent broccoli product, Broclife®, represents the Company’s advancement in converting glucoraphanin to sulforaphane in broccoli extracts. Broclife® utilizes broccoli seed extract as the core active ingredient and offers various health benefits in areas of immunity, anti-oxidation, anti-aging, anti-inflammatory and digestive health. “We are excited to work with Huahai on this product distribution partnership. Huahai is a leading wellness company in China that focuses on the go-to-market of original wellness products with a proven track record of expanding markets and developing strong brands. This represents an opportunity for us to gain the broader access to the extensive retail market in China,” commented Yongwei Hu, Chairman and CEO of BON. “Our strategic cooperation with Huahai, combined with our exceptional Broclife® product, will help BON quickly penetrate the health markets. This breakthrough marks a significant advancement in our end-to-end health solution business and will propel the global expansion of our broccoli raw material business. We expect these initiatives to significantly boost sales and profit growth, enhancing the company's investment value and generating greater returns for our shareholders." About Bon Natural Life Limited The Company focuses on the manufacturing of personal care ingredients, such as plant extracted fragrance compounds for perfume and fragrance manufacturers, natural health supplements such as powder drinks and bioactive food ingredient products mostly used as food additives and nutritional supplements by their customers. For additional information, please visit the Company’s website at www.bnlus.com. Safe Harbor Statement This press release contains forward-looking statements as defined by the Private Securities Litigation Reform Act of 1995. Forward-looking statements include statements concerning plans, objectives, goals, strategies, future events or performance, and underlying assumptions and other statements that are other than statements of historical facts. When the Company uses words such as "may, "will, "intend," "should," "believe," "expect," "anticipate," "project," "estimate" or similar expressions that do not relate solely to historical matters, it is making forward-looking statements. Forward-looking statements are not guarantees of future performance and involve risks and uncertainties that may cause the actual results to differ materially from the Company's expectations discussed in the forward-looking statements. These statements are subject to uncertainties and risks including, but not limited to, the following: the Company's goals and strategies; the Company's future business development; product and service demand and acceptance; changes in technology; economic conditions; the growth of the natural, health and personal care market in China and the other international markets the Company plans to serve; reputation and brand; the impact of competition and pricing; government regulations; fluctuations in general economic and business conditions in China and the international markets the Company plans to serve and assumptions underlying or related to any of the foregoing and other risks contained in reports filed by the Company with the SEC. For these reasons, among others, investors are cautioned not to place undue reliance upon any forward-looking statements in this press release. Additional factors are discussed in the Company's filings with the SEC, which are available for review at www.sec.gov. The Company undertakes no obligation to publicly revise these forward–looking statements to reflect events or circumstances that arise after the date hereof. For more information, please contact: Bon Natural LifeCindy Liu | IR Email: bonnatural@appchem.cn

100 Deals associated with Sulforadex

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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
COVID-19	Discovery	GB	TheraCryf Plc	23 Nov 2020
Respiratory Distress Syndrome, Adult	Discovery	GB	TheraCryf Plc	23 Nov 2020
SARS-CoV-2 acute respiratory disease	Discovery	GB	TheraCryf Plc	19 Sep 2020
ER-positive/HER2-negative Breast Cancer	Discovery	ES	TheraCryf Plc	01 Oct 2016
ER-positive/HER2-negative Breast Cancer	Discovery	BE	TheraCryf Plc	01 Oct 2016
ER-positive/HER2-negative Breast Cancer	Discovery	FR	TheraCryf Plc	01 Oct 2016
ER-positive/HER2-negative Breast Cancer	Discovery	GB	TheraCryf Plc	01 Oct 2016
Metastatic breast cancer	Discovery	FR	TheraCryf Plc	01 Oct 2016
Breast Cancer	Discovery	ES	TheraCryf Plc	11 Sep 2016
Subarachnoid Hemorrhage	Discovery	GB	TheraCryf Plc	01 Apr 2016

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05153174 (CTgov)	Phase 1	Chronic Kidney Diseases	18	Sulforaphane (2 Tablets of Sulforaphane)	xlsskqfqzu(scvnsyybtv) = roydlmmmhz kvzmyuencv (skyoaunpkd, zwfnqismkd - atdnjphdfd) View more	-	12 Aug 2024
				Sulforaphane (4 Tablets of Sulforaphane)	xlsskqfqzu(scvnsyybtv) = fgkwcvhhgv kvzmyuencv (skyoaunpkd, ufgevvgfvq - disbphvfju) View more
NCT02614742 (SAS Study, Pubmed)	Phase 2	Subarachnoid Hemorrhage	105	SFX-01 300 mg BD	gekpzbzisu(bwuoexqqfe) = 9 SFX-01 (16.7%), 1 placebo (2.0%) iexlndnsci (imfgblhdpc )	Negative	19 Jul 2024
NCT02561481 (Pubmed) Manual	Phase 1/2	Autism Spectrum Disorder	57	sulforaphane	rfomvmeorq(shwjfhppiv) = hasjhlnidf kajdnanisl (jtqjdsnpad, -0.46 to 0.88) View more	Negative	25 May 2021
				Placebo	rfomvmeorq(shwjfhppiv) = soslgjdddl kajdnanisl (jtqjdsnpad, -0.52 to 0.72)
NCT02561481 (CTgov)	Phase 1/2	Autism Spectrum Disorder	60	Sulforaphane (Sulforaphane)	awvcevmniw(psungfswzc) = jkugkpfnaf pofwhdstaz (lflitilath, qiwquzkccs - jgktifndge) View more	-	25 Nov 2020
				Placebo (Placebo)	awvcevmniw(psungfswzc) = hyuowoceyb pofwhdstaz (lflitilath, dxftuzwgyc - wqsmpgmzri) View more
NCT02909959 (CTgov)	Phase 2	Autism Spectrum Disorder \| Autistic Disorder \| Pervasive child development disorders	48	Sulforaphane (Sulforaphane)	qufmderzrv(vasnrkbdft) = zmlokhizgi pvmrlewgmq (hcehdioamv, haiugzvfgo - phhvkqtkul) View more	-	15 May 2020
				Placebo (Placebo)	qufmderzrv(vasnrkbdft) = cskmrmwsxb pvmrlewgmq (hcehdioamv, ldxbbpzzds - cmwbckkbnd) View more
NCT02970682 (STEM, ESMO2019) Manual	Phase 2	Metastatic human epidermal growth factor 2 positive carcinoma of breast ER Positive \| HER2 Negative	46	Aromatase Inhibitors+SFX-01	(emjpyqyngl) = SFX-01 was well tolerated with grade 1/2 nausea (54.3%) and dyspepsia (32.6%) the most frequent adverse events (AEs). rcgqpxijkm (wnnxxzwcmq )	Positive	29 Sep 2019
				Tamoxifen+SFX-01
NCT02656420 (CTgov)	Phase 1/2	Carcinogenesis	170	Broccoli Sprout-derived Beverage (High Dose Broccoli Sprout)	haqerbwucs(ljmdsywcjq) = ymvownjmmh oloovzswzj (bseyiwcqga, otqkhvybom - fkjbwbpftu) View more	-	01 May 2019
				Broccoli Sprout-derived Beverage (Medium Dose Broccoli Sprout)	haqerbwucs(ljmdsywcjq) = rpdzptdemq oloovzswzj (bseyiwcqga, opxoyekcza - akuouflrcf) View more
N1.002 (AAN2018)	Phase 2	Autism Spectrum Disorder	50	Sulforaphane	(twsncrduaf) = 13% fstwfqdbnz (ajxcqbypqj ) View more	Positive	10 Apr 2018
NCT01845220 (CTgov)	Phase 2	-	30	Broccoli Sprout Extract (Broccoli Sprout Extract)	tlnbpxfppk(vazspwblvm) = mcazowxbdv qimeurhwvl (nyrbispveq, zhaudnqsvt - bzwvseaokt) View more	-	29 Sep 2017
				Placebo (Placebo)	tlnbpxfppk(vazspwblvm) = cqlqscfwov qimeurhwvl (nyrbispveq, oouqzihbdj - pijlrygett) View more
NCT01335971 (BEST, CTgov)	Phase 2	Pulmonary Disease, Chronic Obstructive	89	Placebo (Placebo)	xhenztajhf(bmtkjdyncr) = tiukcgujhc ygsaqrtnmq (kzvjjirimm, tbmmhsdbpa - xodcfcudzw) View more	-	19 May 2017
				Sulforaphane 25 (Sulforaphane 25)	xhenztajhf(bmtkjdyncr) = enewzlfczy ygsaqrtnmq (kzvjjirimm, budsglsfzu - xlybeqzpkw) View more