Delving into the Latest Updates on Allopurinol with Synapse

Overview

Basic Info

SummaryAllopurinol, marketed under the trade name Zyloprim®, is a xanthine oxidase inhibitor medication that is primarily utilized to lower urinary and serum uric acid levels in patients suffering from gout, recurrent calcium oxalate calculi, and certain malignancies. The mechanism of action of this medication involves inhibiting the enzyme xanthine oxidase. Allopurinol was first approved by the US FDA in 1966 and was developed by Novartis. Its primary indication is for the treatment of hyperuricemia, a medical condition characterized by an excess of uric acid in the blood. Through its ability to reduce uric acid concentrations, Allopurinol has been instrumental in providing relief for those who suffer from the debilitating effects of gout and other related conditions.

Drug Type

Small molecule drug

Synonyms

1,5-Dihydro-4H-pyrazolo(3,4-d)pyrimidin-4-one, 1,5-Dihydro-4H-pyrazolo(3,4-d)pyrimidine-4-one, 1H-Pyrazolo(3,4-d)pyrimidin-4-ol

+ [23]

Target

XO

Action

inhibitors

Mechanism

XO inhibitors(Xanthine dehydrogenase inhibitors)

Therapeutic Areas

Immune System DiseasesCongenital DisordersEndocrinology and Metabolic Disease+ [3]

Active Indication

GoutNephrolithiasisHyperuricemia

Inactive Indication

Acute myocardial infarctionChronic Kidney DiseasesDiabetes Mellitus+ [2]

Originator Organization

Sebela Ireland Ltd.

Active Organization

GlaxoSmithKline KK

Casper Pharma LLC

Sumitomo Pharma Co., Ltd.

+ [1]

Inactive Organization

AstraZeneca PLC

Ardea Biosciences, Inc.

Advancell Advanced In Vitro Cell Technologies SL

Drug Highest PhaseApproved

First Approval Date

United States (19 Aug 1966),

Hyperuricemia

Regulation-

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Structure/Sequence

Molecular FormulaC5H4N4O

InChIKeyOFCNXPDARWKPPY-UHFFFAOYSA-N

CAS Registry315-30-0

African American adults in the United States have the highest prevalence rate of high blood pressure (hypertension) and heart failure in the world. African Americans with treatment resistant hypertension have higher levels of the enzyme - xanthine oxidase compared to Caucasians. This trial will test if administration of the xanthine oxidase inhibitor - Allopurinol (commonly used in the treatment of gout), given over a period of 8 weeks, will improve heart function, exercise ability and quality of life in African American Veterans with resistant hypertension.

Start Date30 Sep 2024

Sponsor / Collaborator

VA Office of Research and Development

100 Clinical Results associated with Allopurinol

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100 Translational Medicine associated with Allopurinol

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100 Patents (Medical) associated with Allopurinol

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11,734

Literatures (Medical) associated with Allopurinol

31 Dec 2025·Renal Failure

Comparative efficacy and safety of febuxostat and allopurinol in chronic kidney disease stage 3–5 patients with asymptomatic hyperuricemia: a network meta-analysis

Review

Author: Wang, Yinglin ; Zhang, Yanyun ; Chen, Jiaojiao ; Chen, Lu

OBJECTIVEThis study evaluates and compares the effectiveness and safety of febuxostat and allopurinol in chronic kidney disease (CKD) stages 3-5 patients with asymptomatic hyperuricemia using a network meta-analysis.METHODSA systematic review and network meta-analysis were conducted, adhering to PRISMA-NMA guidelines. Searches included PubMed, Embase, Cochrane Library, and Chinese databases up to June 2024. Randomized controlled trials (RCTs) and cohort studies were assessed for methodological rigor using GRADE.RESULTSA total of 12 RCTs and 4 cohort studies (n = 2,423 participants) were included. Febuxostat was associated with greater improvements in estimated glomerular filtration rate compared to allopurinol (MD, 4.99 mL/min/1.73 m²; 95%CI -0.65 to 10.78; certainty: low) and placebo (MD, 4.72 mL/min/1.73 m²; 95%CI 0.67 to 8.82; low). Serum uric acid reduction was also more pronounced with febuxostat (MD, -0.61 mg/dL; 95%CI -1.15 to -0.05; moderate). Safety outcomes, including major cardiovascular events and adverse events, showed no significant differences between febuxostat and allopurinol. Subgroup analyses revealed enhanced effectiveness of febuxostat at six months of treatment.CONCLUSIONSThis analysis provides robust evidence that febuxostat might offers greater improvements in kidney function and uric acid levels compared to allopurinol or placebo in asymptomatic hyperuricemia with CKD stage 3-5 patients, without compromising safety. These findings can guide clinical decision-making and treatment optimization.

01 May 2025·International Journal of Biological Macromolecules

Hesperetin acts as a potent xanthine oxidase inhibitor: New evidence from its reactive oxygen suppression and enzyme binding

Article

Author: Liu, Yinying ; Fang, Zhongxiang ; Lu, Hanyu ; Lu, Shengmin

Xanthine oxidase (XO) plays a crucial role in purine metabolism, catalyzing the oxidation of hypoxanthine to xanthine and subsequently to uric acid. Elevated uric acid levels can lead to hyperuricemia, a condition linked to gout, kidney stones, and other chronic diseases. Inhibiting XO activity represents a promising strategy for managing hyperuricemia. This study investigated the inhibitory effects of the flavonoid hesperetin enriched in citrus fruits on XO activity, its antioxidant properties against reactive oxygen species (ROS) generated by the XO reaction, and the underlying mechanisms of enzyme inhibition. Enzyme kinetics and spectroscopy revealed that hesperetin competitively inhibited XO at an inhibition constant of (2.15 ± 0.05) × 10^-6 mol/L through its binding to the molybdopterin active center of XO, preventing the entry of xanthine and the transfer of electrons, effectively scavenging superoxide radicals by inhibiting uric acid production and oxygen reduction, and inducing conformational changes in XO's structure. Fluorescence quenching indicated that hesperetin interacted with XO through a combination of static and dynamic quenching mechanisms. Molecular docking simulations demonstrated that hesperetin binded tightly to XO's active site, blocking substrate entry. Molecular dynamics confirmed that hesperetin stabilized the XO-hesperetin complex through reinforced hydrophobic and hydrogen-bond interactions. The results suggest that hesperetin can act as a potent natural xanthine oxidase inhibitor or a functional food supplement to alleviate hyperuricemia.

01 Apr 2025·European Journal of Haematology

Tumor Lysis Syndrome in Acute Myeloid Leukemia Patients Treated With a Venetoclax Based Regimen

Article

Author: Bruno, Ximena Jordan ; Frey, Noelle ; Martin, Mary Ellen ; Maillard, Ivan ; Hexner, Elizabeth ; Babushok, Daria ; Lai, Catherine ; Pratz, Keith ; Perl, Alexander ; Luger, Selina ; Rowe, Margaret ; Porter, David ; Hossain, Nasheed ; Carulli, Alison ; Hirsh, Rebecca ; Carroll, Martin ; Stadtmauer, Edward ; Matthews, Andrew ; Paralkar, Vikram R ; Gill, Saar ; McCurdy, Shannon ; Loren, Alison

ABSTRACTVenetoclax with hypomethylating agents (HMA) is the standard of care for acute myeloid leukemia (AML) in patients ineligible for intensive chemotherapy and is associated with tumor lysis syndrome (TLS). TLS prophylaxis and the use of Cairo Bishop versus Howard diagnostic criteria are not standardized. Here we report TLS prophylaxis and incidence in a retrospective cohort of 100 consecutive AML patients treated with venetoclax and HMA. Thirty four patients developed laboratory Cairo Bishop TLS; 8 of these met criteria for clinical Cairo Bishop TLS. Only 6 of patients met Howard TLS criteria. Fourteen patients had spontaneous TLS. Ninety two out of 100 patients had a white blood cell count (WBC) < 25 000 cells/μL at treatment start. Prophylaxis like the original venetoclax trial with allopurinol (56%), intravenous fluids (21%), and frequent lab monitoring (56%) was less common. There was a trend toward increased Cairo Bishop TLS in patients with WBC ≥ 15 000 cells/μL. In our study Howard TLS criteria better identified patients with significant TLS. Aggressive TLS prophylaxis was uncommon in our cohort and is likely unnecessary for most patients at low risk of TLS.

46

News (Medical) associated with Allopurinol

29 Jan 2025

·www.globenewswire.com

XORTX to Present at Microcap Conference

CALGARY, Alberta, Jan. 29, 2025 (GLOBE NEWSWIRE) -- XORTX Therapeutics Inc. ("XORTX" or the “Company”) (NASDAQ: XRTX | TSXV: XRTX | Frankfurt: ANUA), a late stage clinical pharmaceutical company focused on developing innovative therapies to treat progressive kidney disease and gout, announces attendance and presentation at the Microcap Conference hosted by DealFlow Events on January 28 through 30, 2025 in Atlantic City, NJ. Attendance at this conference continues outreach to the investment community and provides XORTX with an opportunity to update investors on our newly announced gout program. The presentation on January 29, 2025 will review the Company's plans to advance the XRx-026 program for gout through a New Drug Application (“NDA”) filing, and activities associated with the XRx-008 program for autosomal dominant polycystic kidney disease (“ADPKD”), including registration clinical trial preparations. Dr. Allen Davidoff, XORTX CEO stated, “This conference is designed to give participants one-on-one meetings with new investors as well as the opportunity to present a Company overview to all of the conference attendees. We are excited to be able to reach out to the quality investors who will attend this conference and to elaborate on our exciting plans for bringing our gout program in the near term, and ADPKD programs in the longer term, through to FDA marketing approval.” XORTX’s presentation will be recorded and available after the conference on the Company’s website. About XORTX Therapeutics Inc. XORTX is a pharmaceutical company with three clinically advanced products in development: 1) our lead, XRx-008 program for ADPKD; 2) our XRx-026 program for the treatment of allopurinol intolerant gout; and 3) our secondary program in XRx-101 for acute kidney and other acute organ injury associated with Coronavirus / COVID-19 infection. In addition, XRx-225 is a pre-clinical stage program for Type 2 Diabetic Nephropathy. XORTX is working to advance its clinical development stage products that target aberrant purine metabolism and xanthine oxidase to decrease or inhibit production of uric acid. At XORTX, we are dedicated to developing medications to improve the quality of life and health of kidney disease patients and individuals with gout. Additional information on XORTX is available at www.xortx.com. For more information, please contact: Allen Davidoff, CEONick Rigopulos, Director of Communicationsadavidoff@xortx.com or +1 403 455 7727nick@alpineequityadv.com or +1 617 901 0785 Neither the TSX Venture Exchange nor Nasdaq has approved or disapproved the contents of this news release. No stock exchange, securities commission or other regulatory authority has approved or disapproved the information contained herein. Forward Looking Statements This press release may contain express or implied forward-looking statements pursuant to Canadian and U.S. Federal securities laws. These forward-looking statements and their implications are based on the current reasonable expectations of the management of XORTX only, and are subject to a number of factors and uncertainties that could cause actual results to differ materially from those described in such forward-looking statements. Except as otherwise required by law, XORTX undertakes no obligation to publicly release any revisions or updates to these forward-looking statements to reflect events or circumstances after the date hereof or to reflect the occurrence of unanticipated events. More detailed information about the risks and uncertainties affecting XORTX is contained in the Company’s most recently filed Annual Information Form and the Management Discussion and Analysis for its most recent financial reporting period filed on the Company’s SEDAR profile (www.sedar.com) and under the heading “Risk Factors” in XORTX’s Registration Statement on Form F-1 filed with the Securities and Exchange Commission (“SEC”) available on the SEC's website, www.sec.gov.

24 Jan 2025

·www.fiercepharma.com

Takeda bids adieu to Uloric after gout med's gradual fade from glory

To ease into the discontinuation, Takeda will continue to distribute Uloric to U.S. wholesalers through March 31, 2026, which should provide enough inventory for patients through the end of the year. The journey of Takeda’s gout med Uloric—which turned rocky in recent years—has come to an end in the U.S.This week, the medicine, first approved in 2009, was listed as discontinued on the FDA’s online drug shortage database. The drug, also known as febuxostat, was cleared for chronic management of hyperuricemia—or high uric acid levels in the body—in patients with gout and was previously available in 40-mg and 80-mg tablets.“As a global, R&D-driven biopharmaceutical company, we have taken this decision to help streamline our operational efficiencies and better dedicate our resources where they can provide the most value to patients,” a Takeda spokesperson told Fierce Pharma. Since 2019, multiple generics referencing Uloric have hit the scene in the U.S., with just some 3% of patients using Takeda’s branded product versus generic competitors, the spokesperson added.The move isn’t a total surprise, as the Japanese pharma told the FDA last year it planned to end production of branded Uloric at the end of 2024. To ease into the discontinuation, Takeda will continue to distribute Uloric to U.S. wholesalers through March 31, 2026, which should provide enough inventory for patients through the end of the year, the spokesperson said.Uloric’s sales seem to have peaked in Takeda’s 2019 fiscal year, when the drug brought home 51.1 billion Japanese yen (then around $477 million). The following year, Takeda did not report directly on the drug’s sales, instead noting that revenue beyond its core therapeutic areas dropped 18.5%. The company blamed the issue, in part, on “off-patented products such as Uloric.”Things started to take a turn for Uloric in 2017, when the FDA sent out a drug safety communication to the public signaling the medicine’s potential to cause increased cardiovascular events versus allopurinol—a widely available generic gout drug.Subsequently, safety flags raised in a post-marketing study in 2018 prompted consumer advocacy group Public Citizen to petition the FDA to remove Uloric from the U.S. market. Another blow struck in 2019, when the FDA revoked Uloric’s first-line treatment nod and added a boxed warning that the medication carried an increased risk of death compared to allopurinol.Takeda did not fight the decision, with a spokesperson telling Fierce Pharma at the time that the company found the label updates “appropriate” to ensure doctors and patients had the info to make proper treatment decisions.

Drug ApprovalAccelerated Approval

17 Jan 2025

·www.globenewswire.com

XORTX Announces Change of Auditor

CALGARY, Alberta, Jan. 17, 2025 (GLOBE NEWSWIRE) -- XORTX Therapeutics Inc. ("XORTX" or the “Company”) (NASDAQ: XRTX | TSXV: XRTX | Frankfurt: ANU), a late stage clinical pharmaceutical company focused on developing innovative therapies to treat progressive kidney disease and gout, announces the Company has changed its auditor from Smythe LLP, Chartered Professional Accountants (“Former Auditor”) to Davidson & Company LLP, Chartered Professional Accountants, (“Successor Auditor”) effective January 16, 2025. XORTX’s board of directors accepted the resignation of the Former Auditor, as of January 16, 2025 and appointed the Successor Auditor as the new auditor of the Company effective January 16, 2025, and to hold office until the close of the Company's next annual general meeting of shareholders. There were no reservations in the Former Auditor's audit reports for any financial period during which the Former Auditor was the Company's auditor. There are no "reportable events" (as the term is defined in National Instrument 51-102 - Continuous Disclosure Obligations) between the Company and the Former Auditor. In accordance with National Instrument 51-102, the Notice of Change of Auditor, together with the required letters from the Former Auditor and the Successor Auditor, have been reviewed by the Company's audit committee and board of directors and have been filed on the Company’s SEDAR+ profile at www.sedarplus.ca. About XORTX Therapeutics Inc. XORTX is a pharmaceutical company with three clinically advanced products in development: 1) our lead, XRx-008 program for ADPKD; 2) our XRx-026 program for the treatment of allopurinol intolerant gout; and 3) our secondary program in XRx-101 for acute kidney and other acute organ injury associated with Coronavirus / COVID-19 infection. In addition, XRx-225 is a pre-clinical stage program for Type 2 Diabetic Nephropathy. XORTX is working to advance its clinical development stage products that target aberrant purine metabolism and xanthine oxidase to decrease or inhibit production of uric acid. At XORTX, we are dedicated to developing medications to improve the quality of life and health of kidney disease patients and individuals with gout. Additional information on XORTX is available at www.xortx.com. For more information, please contact: Allen Davidoff, CEO Nick Rigopulos, Director of Communicationsadavidoff@xortx.com or +1 403 455 7727nick@alpineequityadv.com or +1 617 901 0785 Neither the TSX Venture Exchange nor Nasdaq has approved or disapproved the contents of this news release. No stock exchange, securities commission or other regulatory authority has approved or disapproved the information contained herein.

Executive Change

100 Deals associated with Allopurinol

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External Link

KEGG	Wiki	ATC	Drug Bank
D00224	Allopurinol	M04AA01	DB00437

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Gout	China	Jiangsu Meitong Pharmaceutical Co. Ltd.	01 Jan 1985
Nephrolithiasis	China	Jiangsu Meitong Pharmaceutical Co. Ltd.	01 Jan 1985
Hyperuricemia	United States	Casper Pharma LLC	19 Aug 1966

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Chronic Kidney Diseases	Phase 2	Spain	AstraZeneca PLC	23 Jul 2019
Chronic Kidney Diseases	Phase 2	Israel	AstraZeneca PLC	23 Jul 2019
Chronic Kidney Diseases	Phase 2	Romania	AstraZeneca PLC	23 Jul 2019
Gout	Phase 2	United States	Ardea Biosciences, Inc.	28 Jul 2015
Hand-Foot Syndrome	Phase 2	Belgium	Advancell Advanced In Vitro Cell Technologies SL	01 Feb 2011
Hand-Foot Syndrome	Phase 2	Italy	Advancell Advanced In Vitro Cell Technologies SL	01 Feb 2011
Hand-Foot Syndrome	Phase 2	Spain	Advancell Advanced In Vitro Cell Technologies SL	01 Feb 2011
Hand-Foot Syndrome	Phase 2	Germany	Advancell Advanced In Vitro Cell Technologies SL	01 Feb 2011
Acute myocardial infarction	Phase 2	United States	AstraZeneca PLC	01 Jul 2005
Diabetes Mellitus	Phase 2	United States	AstraZeneca PLC	01 Jul 2005

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


UEGW2024	Not Applicable	Inflammatory Bowel Diseases 6-TGN \| 6-MMP \| FC (fecal calprotectin)	237	Low-dose azathioprine plus allopurinol	(wtrdfvgbal): OR = 2.46 (95% CI, 1.43 - 4.25), P-Value = 0.001	Positive	13 Oct 2024
				Azathioprine monotherapy
ESC2024	Not Applicable	-	-	Allopurinol + hydration	dohvprgngo(mtpytwkgca) = ujlrbxpert cgbigixcfy (ksijttpgvo )	-	31 Aug 2024
				allopurinol (Hydration only)	dohvprgngo(mtpytwkgca) = mzjbharaid cgbigixcfy (ksijttpgvo )
NCT05119686 \| NCT05253833 (AR882-203, PRNewswire) Manual	Phase 2	Gout	-	AR882 50 mg	(mynkwnjuru) = xybiuzxgaa eqqxyeyagm (qmcmkjoect ) View more	Positive	23 Aug 2024
				AR882 75 mg	(mynkwnjuru) = dgpsuhfxqt eqqxyeyagm (qmcmkjoect ) View more
NCT04327024 (AMETHYST, Pubmed \| JAMA Cardiol) Manual	Phase 2	Heart failure with normal ejection fraction	159	Verinurad plus Allopurinol	(uiaqlgrynt) = eqlfesswlu qcpemazqco (zqdlnonhhf, -0.56 to 1.10) View more	Negative	14 Aug 2024
				Allopurinol	(uiaqlgrynt) = cosmvhgqxs qcpemazqco (zqdlnonhhf, -1.03 to 0.69) View more
NCT05253833 (EULAR 12024 \| EULAR 22024) Manual	Phase 2	Arthritis, Gouty	42	AR882 75 mg	(zdjtguajxu) = idqpahjlgh zxcbypunzy (xhojuaelna ) View more	Positive	12 Jun 2024
				AR882 50 mg + allopurinol	(zdjtguajxu) = guxdkgskrp zxcbypunzy (xhojuaelna ) View more
EULAR2024	Not Applicable	fractional excretion of uric acid (FEUA)	1,465	Allopurinol	cknhgpuruc(svwvnmnmpq) = otrgdbkyns prptiivgpo (voqbrnkqxb ) View more	Positive	05 Jun 2024
				Febuxostat	cknhgpuruc(svwvnmnmpq) = pibreysidl prptiivgpo (voqbrnkqxb )
ISN WCN2024	Not Applicable	Chronic Kidney Diseases serum uric acid levels ≥6 mg/dl	5,000	Allopurinol 100 mg/day	iawrujzphd(ctuptrjcve) = qvkktabbdj ewddugbvnq (mkrbmpmgdh ) View more	Positive	01 Apr 2024
ACR2023	Not Applicable	-	-	Allopurinol (Asian patients)	dpvosfykzg(etzxiwsszq) = jjbhbnjlaf rebmlyxjiy (zcvpukvjuj )	-	12 Nov 2023
				Allopurinol (Black patients)	dpvosfykzg(etzxiwsszq) = ynvsuwhyka rebmlyxjiy (zcvpukvjuj )
AR882-203 (Biospace) Manual	Phase 2	Chronic tophaceous gout	42	AR882 75mg	(gwfavaitgg) = afsknoavpi acvzqpkoib (vqxyqrkffz ) View more	Positive	08 Nov 2023
				AR882 50mg+allopurinol	(gwfavaitgg) = kpnovoqvfp acvzqpkoib (vqxyqrkffz ) View more
ESMO2023	Not Applicable	Neoplasms	715	Rasburicase	wpfpldcdue(ayltlxomfe) = kfbkbjkhue oqmpyogqec (xncpigwqoc ) View more	-	23 Oct 2023
				Allopurinol	wpfpldcdue(ayltlxomfe) = bebnpbpzvp oqmpyogqec (xncpigwqoc ) View more