Our preclinical study confirmed that copper accumulation can lead to radioresistance in vitro and in vivo, and reducing the concentration of copper with copper chelator help to overcome radioresistance. Therefore, the investigators plan to carry out a prospective interventional phase II clinical trial to explore the safety and efficacy of penicillamine (a common copper chelator) as a radiosensitizer in the treatment of recurrent head and neck cancer.

Start Date15 Nov 2023

Sponsor / Collaborator

Nanfang Hospital

IRCT20200407046981N49 / SuspendedIIT

Comparative bioequivalence study of the Penicillamine 250-mg Capsules manufactured by Vana Darou Gostar Company with Penicillamine brand capsules (Cupripen®) by Laboratorios Rubio company

Start Date11 Dec 2022

Sponsor / Collaborator-

NCT03957720 / RecruitingEarly Phase 1IIT

The Individual Therapy for Patients With Wilson's Disease

Based on the genotype characteristics and genotype-phenotype-treatment prognosis data of Chinese WD patients, this study intends to further optimize the treatment regimen of Chinese WD patients and formulate individualized treatment regimens for each genotype, so as to further improve the prognosis of patients.

Start Date15 Mar 2019

Sponsor / Collaborator

The Second Affiliated Hospital Zhejiang University School of Medicine

100 Clinical Results associated with Penicillamine

100 Translational Medicine associated with Penicillamine

100 Patents (Medical) associated with Penicillamine

5,746

Literatures (Medical) associated with Penicillamine

01 Feb 2025·TALANTA

Cu-NC single-atom nanozymes with peroxidase-like activity for colorimetric detection of d-penicillamine

Article

Author: Yang, Xiupei ; Fan, Yuxiu ; Xie, Xiaoyi ; Wang, Ya ; Jiang, Ling ; Zhang, Chenglin

Most conventional nanozymes have poor specificity and low activity, and designing high-performance nanozymes remains a challenge. In contrast, single-atom nanozymes have high atom utilization and high reactivity. Here, we prepared Cu single-atom nanozymes (Cu-NC) with excellent peroxidase-like activity by high-temperature pyrolysis using Cu as a transition metal source. The introduction of Cu formed the Cu-N_x active site, which accelerated charge transfer between the reactants and the active site and was the key for improving the activity. With Cu-NC as a catalyst, H₂O₂ rapidly oxidized 3,3',5,5'-tetramethylbenzidine (TMB) to oxTMB, and the solution turned blue with strong absorption at 652 nm. Because d-penicillamine (D-PA) can reduce oxTMB or react with reactive oxygen species radicals to inhibit the color reaction, we built a colorimetric sensing platform around Cu-NC for the determination of D-PA and successfully used it for the determination of D-PA in urine samples. This work provides new ideas for the design of high-performance nanozymes and the detection of D-PA in real environments.

01 Jan 2025·COLLOIDS AND SURFACES B-BIOINTERFACES

Monitoring cancer treatments in melanoma cells using a fluorescence lifetime nanoprobe based on a CdSe/ZnS quantum dot functionalized with a peptide containing D-penicillamine and histidine

Article

Author: Garzón-Ruiz, Andrés ; Herrera-Ochoa, Diego ; Bravo, Iván

Anticancer therapies with cisplatin and volasertib (BI-6727) were monitored by fluorescence lifetime imaging microscopy (FLIM) in live SK-Mel-2 melanoma cells. A CdSe/ZnS quantum dot functionalized with a peptide containing D-penicillamine and histidine (CdSe/ZnS-PH) was used as intracellular pH fluorescent probe. A faster cytosol acidification was observed for cells treated with cisplatin when compared to volasertib. The first changes in the intracellular pH were found after 2 hours of treatment with cisplatin and 8 hours with volasertib. Additionally, the relationship between cytosol acidification and apoptosis was investigated using an innovative methodology based on time-resolved fluorescence measurements. Similar low percentages of apoptotic cells were observed after short incubation periods (2 - 8 hours) with both drugs. In contrast, late apoptosis and death were found for a large fraction of cells during 24-hour incubation with cisplatin but not volasertib. Thus, the early acidification observed in cisplatin treatment could accelerate apoptosis and cell death. Despite volasertib treatment shows slower mechanism of action than cisplatin, similar inhibitory effects were found for both drugs at longer incubation periods (72 hours). This study proves the potential of CdSe/ZnS-PH nanoparticle as a fluorescence lifetime probe in the study of the mechanism of action of antitumor drugs.

01 Jan 2025·BIOSENSORS & BIOELECTRONICS

Developing oxygen vacancy-rich CuMn2O4/carbon dots dual-function nanozymes via Chan-Lam coupling reaction for the colorimetric/fluorescent determination of D-penicillamine

Article

Author: Huang, Yuming ; Feng, Min ; Zhang, Xiaodan

Defect engineering is a promising approach to construct high performance nanozymes due to its ability to regulate their physical and chemical properties. However, how to construct defects to improve the activity of nanozymes remains a challenge. Herein, for the first time, the Chan-Lam coupling reaction is used to construct the oxygen vacancy (O_V)-rich CuMn₂O₄/carbon dots (CDs) (O_V-CuMn₂O₄/CDs) dual-function nanozymes with fluorescent (FL) and oxidase-like properties, via regulating the low-valent metal ions (Cu⁺ and Mn²⁺) and O_v contents in the spinel CuMn₂O₄ and in-situ growth of β-cyclodextrin (β-CD)-derived CDs. Expectedly, relative to CuMn₂O₄, the O_V-CuMn₂O₄/CDs exhibited 35.8%, 8.5%, and 14.6% rise in the contents of Cu⁺, Mn²⁺ and O_v, respectively. Abundant O_v provides more O₂ adsorption/activation sites, and the charge transfer between O_v and metal atoms increases the charge density around metal atoms. This produces more low-valent metals (like Cu⁺ and Mn²⁺) to promote the electron transfer from metal to O atoms and O-O bond cleavage. Thus, the oxidase-like activity of O_V-CuMn₂O₄/CDs is 4.1 times that of CuMn₂O₄. Also, the in-situ growth of β-CD-derived carbon dots on CuMn₂O₄ endows O_V-CuMn₂O₄/CDs selective target recognition. Thus, a sensitive and selective colorimetric and fluorescence dual-mode method was established for determining D-penicillamine (D-PA), with the limit of detection of 0.25 and 0.048 μM, respectively. The method was applied to D-PA determination in real samples. This work demonstrates the Chan-Lam coupling reaction can be used to construct high performance nanozymes for developing dual-mode sensor for the detection of targets.

News (Medical) associated with Penicillamine

28 Oct 2024

·www.globenewswire.com

Monopar Announces Agreement with Alexion, AstraZeneca Rare Disease For Late-Stage Wilson Disease Drug Candidate

Oct. 24, 2024 -- Monopar Therapeutics Inc. (Nasdaq: MNPR), a clinical-stage biotechnology company focused on developing innovative treatments for patients with unmet medical needs, today announced that it has entered into an agreement with Alexion, AstraZeneca Rare Disease for an exclusive worldwide license to ALXN-1840 (bis-choline tetrathiomolybdate), a drug candidate for Wilson disease that Alexion has progressed through a Phase 3 clinical trial that met its primary endpoint. Monopar will be responsible for all future global development and commercialization activities. Chandler D. Robinson, MD, Co-Founder and Chief Executive Officer of Monopar previously researched tetrathiomolybdate at the laboratory bench, published his results in Science, and helped launch a company around what became known as ALXN-1840. The focus was on Wilson disease. Dr. Robinson came to know the Wilson disease community well through his efforts. At the Wilson Disease Association’s request, he delivered the keynote address at their 2013 Annual Conference celebrating their 30th anniversary, sharing his experience helping advance ALXN-1840 from the laboratory bench to patients. In 2023, Alexion terminated the ALXN-1840 program in Wilson disease based on review of results from Phase II mechanistic trials and discussions with regulatory authorities. Chris Starr, PhD, Co-Founder and Executive Chair of Monopar said, “Upon the 2023 announcement, Chandler, due to his long history with the program and the continued high level of unmet medical need, was contacted by Wilson disease patients, executives and board members of the Wilson Disease Association, as well as physicians regarding the potential for Monopar to obtain rights to ALXN-1840. Due in no small measure to the testimonials Chandler received from clinical trial patients who reported benefit while on the drug for years, we decided that this was an opportunity Monopar needed to pursue, and it fits well with my rare disease drug development and commercialization background as well as Chandler’s background.” Dr. Starr also previously co-founded the orphan drug companies BioMarin and Raptor Pharma (acquired by Horizon Pharma, now a part of Amgen). Dr. Robinson commented, “Alexion has generated a substantial clinical data package on ALXN-1840, including a completed Pivotal Phase 3 clinical trial. The medical data gathered from Alexion’s clinical trials furthers our understanding of Wilson disease and stands to benefit this community.” Under the terms of the license agreement, Monopar will pay Alexion an upfront in the form of a cash payment and equity in Monopar. Future payments are based on tiered royalties on net sales and pre-determined regulatory and sales milestones. “We are excited to have Alexion and AstraZeneca as partners of Monopar as, in addition to Alexion’s work in Wilson disease, AstraZeneca maintains a significant presence in the radiopharma field, in which Monopar is committed to continue growing as Monopar recently announced positive human clinical data with our novel radiopharma program (link),” stated Andrew Cittadine, Chief Operating Officer of Monopar. Wilson disease is a rare and progressive genetic condition in which the body’s pathway for removing excess copper is compromised. 1 It affects one in 30,000 live births in the US.1 Over time this results in the build-up of toxic copper levels in the liver, brain, and other organs, leading to damage that greatly impacts a patient’s life. 1 Patients can develop a wide range of symptoms, including liver disease and/or psychiatric or neurological symptoms, such as personality changes, tremors and difficulty walking, swallowing or talking. 1 In some cases, the damage and loss of function may be irreversible. 1,2,3 ALXN-1840 (bis-choline tetrathiomolybdate) is an investigational once-daily, oral medicine in development for the treatment of Wilson disease. This novel molecule is designed to selectively and tightly bind and remove copper from the body’s tissues and blood. ALXN-1840 has been granted Orphan Drug Designation in the United States and orphan designation in the European Union for Wilson disease. The FoCus trial was a pivotal Phase 3, randomized, rater-blinded, multi-center clinical trial designed to evaluate the efficacy and safety of ALXN-1840 versus standard-of-care (SoC) in patients with Wilson disease aged 12 years and older. The primary endpoint assessed copper mobilization over 48 weeks, defined as daily mean AUEC (Area Under the Effect Curve) for dNCC (directly measured non-ceruloplasmin-bound copper). In the trial, 214 patients were enrolled in one of two cohorts on a 3:1 basis (treatment-experienced:treatment-naïve). Each cohort was then randomized 2:1 (ALXN1840:SoC). The first cohort enrolled 161 patients who received SoC (chelation therapy with penicillamine or trientine, zinc therapy or a combination of both chelation and zinc therapy) for more than 28 days and the second cohort enrolled 53 patients who were treatment-naïve or had received SoC for 28 days or less. The FoCus trial met its primary endpoint demonstrating three-times greater copper mobilization from tissues compared to the SoC arm (Least Square Mean Difference [LSM Diff] 2.18 µmol/L; p Monopar Therapeutics is a clinical-stage biotechnology company with late-stage ALXN-1840 for Wilson disease, and radiopharma programs including Phase 1-stage MNPR-101-Zr for imaging advanced cancers, and Phase 1a-stage MNPR-101-Lu and late preclinical-stage MNPR-101-Ac225 for the treatment of advanced cancers. For more information, visit: www.monopartx.com. References: 1. Patil, M., et al. (2013) J Clin Exp Hepatol, 3, 321-336. 2. Roberts, E.A., Schilsky, M.L. American Association for the Study of Liver D. (2008). Diagnosis and treatment of Wilson disease: An update. Hepatology, 47(6), 2089-2111. 3. European Association for the Study of the Liver. (2012). EASL clinical practice guidelines: Wilson’s disease. J Hepatol, 56(3), 671-685. The content above comes from the network. if any infringement, please contact us to modify.

Clinical ResultLicense out/inOrphan Drug

19 Aug 2024

·www.prnewswire.com

Behind The Mystery Unveils Treatment in Wilson Disease with Cuviror® by Orphalan

Wilson Disease, a rare, genetic disorder, hampers the body's ability to eliminate copper, leading to serious health issues. Cuvrior® (trientine tetrahydrochloride) is the only FDA-approved treatment in nearly 30 years. FORT LAUDERDALE, Fla., Aug. 19, 2024 /PRNewswire/ -- This special episode of Behind the Mystery features insightful discussions with a dedicated physician, an advocacy leader, and a CEO whose company has pioneered the first FDA approved treatment for Wilson Disease in nearly 30 years. Mandy, diagnosed with Wilson Disease at a young age, shares her journey living with the condition on the show, addressing the challenges faced by patients in managing their treatment regimens and the need for more convenient options. In addition, Hepatologist Dr. Cheung delves into the complexities of Wilson Disease, including its genetic origins, symptoms, and the critical importance of early diagnosis, management, and adherence to treatment. "I'm proud to be part of the 'Behind the Mystery' team, where we use our platform to raise awareness for the rare disease community. Our series underscored the immense challenges faced by patients, as well as the dedication of physicians, the pharmaceutical industry, and advocacy leaders to provide meaningful solutions to the community," said Senior Writer and Producer of Behind the Mystery, Brittany Cocilova. Our latest episode highlights Orphalan's commitment to developing the only FDA-approved therapy for Wilson Disease in nearly 30 years, showcasing the continued efforts to help patients living with and managing their rare disease. Hosts Montel Williams and Olga Villaverde spotlight the Wilson Disease Association's (WDA) efforts to support patients, improve awareness, and facilitate access to developments. Rhonda Rowland, VP of the WDA, discusses the evolution of treatment options and the organization's role in fostering partnerships between patients, physicians, and the pharmaceutical industry. "Orphalan has a tremendous commitment to educating not only the Wilson Disease community and the general public, but also physicians," says Rhonda Rowland, Vice President of Wilson Disease Association. "We've seen a partnership evolve between advocacy and the pharmaceutical industry which enables an open line of communication addressing the unmet needs in our community." Dr. Naseem Amin, CEO of Orphalan, details how Orphalan is addressing unmet needs in the patient community and emphasizes the importance of empathy in the pharmaceutical industry. CUVRIOR®, a treatment marketed by Orphalan, offers a twice-daily dosing and is a non-refrigerated option for long-term maintenance therapy for Wilson Disease. Behind the Mystery - Wilson Disease will air on Lifetime on August 19th and August 27th at 7:30 AM ET/PT and will remain on the website. By sharing these intimate narratives, the series aims to educate the public, inspire empathy, and advocate for better research, treatments, and support systems. INDICATION CUVRIOR is a copper chelator indicated for the treatment of adult patients with stable Wilson Disease who are de-coppered and tolerant to penicillamine. IMPORTANT SAFETY INFORMATION Do not use CUVRIOR if you are allergic to trientine or to any of the ingredients in CUVRIOR. Your Wilson's Disease symptoms could get worse when you start treatment. This could happen because too much copper is removed from the body in a short period of time. Your doctor may need to reduce your dose or stop CUVRIOR treatment. Copper deficiency may develop following treatment with CUVRIOR. Your doctor will do tests to monitor your urine and blood for copper. Iron deficiency may develop while taking CUVRIOR. If this happens, your doctor may tell you to take iron supplements for a limited time. Allergic reactions, such as a rash, have been reported with trientine, the active ingredient in CUVRIOR. If a rash or other allergic reaction occurs, stop taking CUVRIOR and get emergency medical help. The most common side effects are pain in the abdomen, change in bowel habits, rash, hair loss (alopecia), and mood swings. Take CUVRIOR at least 1 hour apart from any other oral medicine. Tell your doctor about all the medicines you're taking, including over-the-counter medicines, vitamins, and herbal supplements. Avoid taking supplements when taking CUVRIOR. Taking CUVRIOR with mineral supplements (e.g., iron, zinc, calcium, magnesium) can reduce the effectiveness of CUVRIOR. If iron supplementation is necessary, take CUVRIOR at least 2 hours before or 2 hours after taking iron; for other mineral supplements (e.g., zinc, calcium, magnesium), take CUVRIOR at least 1 hour before or 2 hours after. Do not start or stop any medicines while taking CUVRIOR without talking to your doctor. These are not all the possible side effects of CUVRIOR. You are encouraged to report negative side effects of prescription drugs. Contact Orphalan at 1-800-961-8320 or [email protected] or FDA at 1-800-FDA-1088 or medwatch. Please see full Prescribing Information at: About Behind the Mystery: Behind the Mystery™ is the first and only television series dedicated to raising awareness about rare and genetic diseases through powerful patient storytelling. Each episode delves into the personal journeys of individuals and families affected by these conditions, highlighting their struggles, triumphs, and daily realities. By sharing these intimate narratives, the series aims to educate the public, inspire empathy, and advocate for better research, treatments, and support systems. Behind the Mystery not only sheds light on the medical aspects of rare diseases but also celebrates the resilience and strength of the human spirit. Join us weekday mornings on Lifetime®. About Orphalan Orphalan is an international orphan drug development and commercialization company headquartered in Paris. Founded in 2011, the company develops innovative therapies for people living with rare and debilitating diseases. Our trientine tetrahydrochloride product for the treatment of Wilson disease is approved and available in more than 20 countries, branded as CUPRIOR® in EU, the UK, Saudi Arabia, Switzerland, Columbia and China, and as CUVRIOR® in the United States. For more information visit and follow us on LinkedIn. SOURCE Behind The Mystery

Orphan DrugDrug Approval

18 Jan 2024

·www.globenewswire.com

Orphalan announces China NMPA’s approval of its trientine tetrahydrochloride product for the treatment of Wilson disease

Orphalan announces China NMPA’s approval of its trientine tetrahydrochloride product for the treatment of Wilson disease Paris, France 18 January, 2024 - Orphalan SA (“Orphalan” or “the Company”), an international orphan drug development and commercialization company, today announces the approval of its trientine tetrahydrochloride product by China's National Medical Products Administration (NMPA). This product, already marketed as Cuprior® in the EU, the UK, Saudi Arabia, Switzerland, and Colombia, and as Cuvrior® in the US, represents the first trientine approved by the NMPA. It offers a new treatment option for Wilson disease in children aged five years and older and adults intolerant to penicillamine therapy. China is home to an estimated 80,000 individuals with Wilson disease, of whom approximately half have their diagnosis confirmed, and 25,000 are receiving regular treatment. The introduction of new treatment alternatives such as Orphalan’s trientine tetrahydrochloride, particularly for patients who are intolerant to currently available therapies, presents a significant opportunity to meet the needs of a broader segment of the Wilson disease population in China. Orphalan anticipates its product to be available in the country in the coming months. Dr Naseem Amin, Chief Executive Officer at Orphalan, said: “We are pleased with the marketing authorisation approval of our trientine tetrahydrochloride product in China, which offers a well-tolerated and effective treatment option for patients with Wilson disease. This approval is a crucial step towards providing a much-needed treatment option for the Wilson disease community in China and reaffirms our commitment to improving the experience for patients living with rare diseases worldwide.” Yan Qin, Director of Wuhan Tongxin (Wilson disease patient group in China) added: “We were thrilled when we heard that NMPA approved Orphalan's trientine tetrahydrochloride in China. It is a significant step for those of us living with Wilson disease, representing a much-needed alternative treatment option. This approval, a result of Orphalan's patient-focused approach, offers us a chance to better manage our condition with a new, effective treatment.” Wilson disease is a rare inherited disorder of copper transport primarily affecting the liver and brain. Early treatment with legacy agents such as D-penicillamine (DPA), trientine HCI, and zinc salts can effectively slow the progression of the disease, however these options may not be suitable for long-term care due to adverse events associated with DPA and the need for close monitoring during treatment with zinc salts and DPA. ENDS About Orphalan Orphalan is an international orphan drug development and commercialization company headquartered in Paris. Founded in 2011, the Company develops and deliver innovative therapies for people living with rare and debilitating diseases. Our trientine tetrahydrochloride product has been approved for the treatment of Wilson disease and is available in more than 20 countries, branded as Cuprior® in EU, the UK, Saudi Arabia, Switzerland and Columbia, and as Cuvrior® in the United States. For more information visit www.orphalan.com and follow us on LinkedIn. For more information, please contact: Orphalan: Géraldine van den Broek, Head of Corporate & BD Tel: +33 (0)1 42 49 82 64 info@orphalan.com ICR Consilium: Tracy Cheung, Sukaina Virji, Davide Salvi Tel: +44 (0) 203 709 5700 orphalan@consilium-comms.com

Drug ApprovalOrphan Drug

100 Deals associated with Penicillamine

External Link

KEGG	Wiki	ATC	Drug Bank
D00496	Penicillamine	M01CC01	DB00859

R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Heavy Metal Poisoning	CN	Sichuan Pharmaceutical Co., Ltd.	01 Jan 1981
Lead Poisoning	CN	Sichuan Pharmaceutical Co., Ltd.	01 Jan 1981
Cystinuria	US	Bausch Health Cos., Inc.	04 Dec 1970
Hepatolenticular Degeneration	US	Bausch Health Cos., Inc.	04 Dec 1970
Rheumatoid Arthritis	US	Bausch Health Cos., Inc.	04 Dec 1970

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ESGCT2023	Not Applicable	Hepatolenticular Degeneration	-	D-penicillamine (DPA)	dcvtjqaxti(jizopfnsbr) = xkffocpphb senczrfgyx (rulphxrnjr ) View more	-	24 Oct 2023
				VTX-801	dcvtjqaxti(jizopfnsbr) = xhvsddhwpi senczrfgyx (rulphxrnjr )
ASN2020	Not Applicable	Hepatolenticular Degeneration antimyeloperoxidase(MPO)-ANCA \| antinuclear factors \| anti- proteinase(PR3) antibody ... View more	-	D-Penicillamine	kjmjfsnrjj(jsxewnnlnn) = Oral zinc acetate was once truncated due to gastroenterological side effect tnsgdmiigb (olnjtavxjz )	-	19 Oct 2020
				Methyl-prednisolone
MDS2020	Not Applicable	-	-	D-penicillamine	uckkmwasiv(nkoryghbmk) = fayzhoajji evdqovocci (habrlhnhlc ) View more	Negative	12 Sep 2020
ACR2015	Not Applicable	-	-	Non-biologic DMARDs	fgbozstswk(zkzhgwritk) = sxbooxgzzq nhkbyquuem (pyohtpnlrj, 13.4) View more	-	10 Nov 2015
				Biologic DMARDs	fgbozstswk(zkzhgwritk) = jwnfhkovju nhkbyquuem (pyohtpnlrj, 7.4) View more
EAN	Not Applicable	Hepatolenticular Degeneration	33	d-penicillamine (Compliant patients)	wumbpvcbtg(onrqfawetf) = zoxmhikfsa tazsvablro (hsfddlhpgn )	Positive	29 Jun 2015
				d-penicillamine (Non-compliant patients)	wumbpvcbtg(onrqfawetf) = ctokazfloz tazsvablro (hsfddlhpgn )
EULAR2014	Not Applicable	Eosinophilic Fasciitis	16	D-Penicillamine plus Corticosteroids	xcumsvvczq(btvvmsprhd) = proteinuria was unexpectedly common in both groups although it was more frequent in the D-Pen plus CS group wyofnmqhzz (empjyiiqzg ) View more	-	11 Jun 2014
				Corticosteroids alone
ASN2011	Not Applicable	Toxicity \| Renal cyst	-	D-Penicillamine	ddcikkeuon(gysmlqzxna) = including loosening of the skin, keratoconus, popliteal aneurysms, cutix laxa, cardiomyopathy, restrictive lung disease, thickening of the walls of the esophagus and duodenum vgdjrmjdwq (oipvijmtso ) View more	-	08 Nov 2011

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