Delving into the Latest Updates on Lopinavir/Ritonavir with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

ABT-378/Ritonavir, DARE-HPV, LPV/RTV

+ [10]

Target

HIV-1 pol

Mechanism

HIV-1 pol inhibitors(Human immunodeficiency virus type 1 protease inhibitors)

Therapeutic Areas

Immune System DiseasesInfectious DiseasesUrogenital Diseases

Active Indication

HIV InfectionsHuman Papillomavirus Infection

Inactive Indication

CoinfectionCOVID-19Hepatitis C

Originator Organization

AbbVie, Inc.

Active Organization

AbbVie Deutschland GmbH & Co. KG

AbbVie, Inc.

Viatris, Inc.

+ [1]

Inactive Organization

Abbott Laboratories

Bristol Myers Squibb Co.

Drug Highest PhaseApproved

First Approval Date

US (15 Sep 2000),

HIV Infections

RegulationOrphan Drug (JP), Priority Review (US), Accelerated Approval (US)

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Structure

Molecular FormulaC37H48N4O5

InChIKeyKJHKTHWMRKYKJE-SUGCFTRWSA-N

CAS Registry192725-17-0

View All Structures (2)

The goal of this clinical study is to provide continued access to the study drug(s) to children and adolescents with human immunodeficiency virus type 1 (HIV-1) who completed their participation in an applicable parent study and to monitor for adverse events.
The primary objectives of this study are as follows:
* To provide continued access to the study drug received in the parent protocol or switch to bictegravir/emtricitabine/tenofovir (B/F/TAF) for participants who completed a Gilead parent study evaluating drugs for HIV treatment.
* To evaluate the safety of the study drug(s) in participants with HIV-1.

Start Date27 Aug 2024

Sponsor / Collaborator

Gilead Sciences, Inc.

NCT05334004 / RecruitingPhase 1

A Phase I Study of Intra-anally Administered Lopinavir/Ritonavir in People Living With HIV (PLWH) With High-Grade Anal Intraepithelial Neoplasia (AIN 2/3)

This study is being done to assess the safety of lopinavir/ritonavir in patients with PLWH with AIN. 30 participants will be recruited and can expect to be on active study for approximately 3 months and long term follow up for 40 weeks.

Start Date19 Dec 2023

Sponsor / Collaborator

University of Wisconsin Madison

100 Clinical Results associated with Lopinavir/Ritonavir

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100 Translational Medicine associated with Lopinavir/Ritonavir

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100 Patents (Medical) associated with Lopinavir/Ritonavir

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1,313

Literatures (Medical) associated with Lopinavir/Ritonavir

01 Jan 2025·Talanta

Comparative study of two MIP-based electrochemical sensors for selective detection and quantification of the antiretroviral drug lopinavir in human serum

Article

Author: Erdoğan, Taner ; Al Faysal, Abdullah ; Gölcü, Ayşegül ; Cetinkaya, Ahmet ; Ozkan, Sibel A ; Ozkan, Sibel A.

Thermal polymerization (TP) and electropolymerization (EP) are the two methods used in this study to explore the molecular imprinting process. To detect the antiviral medication lopinavir (LPV), an inhibitor of enzyme HIV-1 protease that is co-formulated with ritonavir (RTV) to extend its half-life in the body, with greater precision, these methods were merged with an electrochemical sensor. The sensors were created on glassy carbon electrodes (GCE) based on molecularly imprinted polymers (MIP) using TP with methacrylic acid (MAA) functional monomer and EP with p-aminobenzoic acid (PABA) functional monomer. Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and electrochemical methods were utilized to examine the technical features of the suggested sensors. For both approaches, the necessary optimization investigations were carried out. Different LPV concentrations, ranging from 1.0 pM to 17.5 pM in drug solution and commercial human serum samples, were used to validate the analytical efficiency of the two sensors and compare their electroanalytical behaviour. For TP-LPV@MIP/GCE and EP-LPV@MIP/GCE, the corresponding limit of detection (LOD) was 2.68 × 10^-13 M (0.169 pg mL^-1) and 1.79 × 10^-13 M (0.113 pg mL^-1) in standard solutions, and 2.87 × 10^-13 M (0.180 pg mL^-1) and 2.91 × 10^-13 M (0.183 pg mL^-1) in serum samples. For the measurement of LPV in tablet form and serum samples, the proposed TP-LPV@MIP/GCE and EP-LPV@MIP/GCE sensors provide good recovery, demonstrating 99.85-101.16 % and 100.36-100.97 % recovery, respectively. The imprinting factor was utilized to demonstrate the selectivity of the suggested sensors by utilizing several anti-viral drugs that are structurally comparable to LPV. Additionally, the constructed sensors were examined for the potential impacts of interferences and the stability during the storage.

06 Dec 2024·Journal of Biomolecular Structure and Dynamics

The binding mechanism of failed, in processing and succeed inhibitors target SARS-CoV-2 main protease

Article

Author: Tang, Bowen ; Huang, Junjie ; Wang, Xiaofeng ; He, Fengming ; Niu, Zhangming ; Chao, Ma ; Wu, Tong ; Hongyu, Hu

Since the outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), several variants have caused a persistent pandemic. Consequently, it is crucial to develop new potential anti-SARS-CoV-2 drugs with specificity. To minimize potential failures and preserve valuable clinical resources for the development of other useful drugs, researchers must enhance their understanding of the interactions between drugs and SARS-CoV-2. While numerous crystal structures of the SARS-CoV-2 main protease (SCM) and its inhibitors have been reported, they provide only static snapshots and fail to capture the dynamic nature of SCM/inhibitor interactions. Herein, we conducted molecular dynamics simulations for five SCM complexes: ritonavir (SCM/RTV), lopinavir (SCM/LPV), the identified inhibitor N3 (SCM/N3), the approved inhibitor ensitrelvir (SCM/ESV), and the approved drug nirmatrelvir (SCM/NMV). Additionally, we explored the potential for covalent bond formation in the N3 and NMV inhibitors through QM/MM calculations using Umbrella sampling. The results show that the binding site is highly flexible to fit those five different inhibitors and each compound has its unique binding mode at the same binding site. Moreover, the binding affinities of positive and negative inhibitors to SCM exhibit significant differences. By gaining insights into the dynamics, we can potentially elucidate why lopinavir/ritonavir, initially considered promising, failed to effectively treat COVID-19. Furthermore, understanding the mechanistic aspects of N3 and NMV inhibition on SCM not only contributes to rational drug discovery against COVID-19 but also aids future studies on the catalytic mechanisms of main proteases in other novel coronaviruses.Communicated by Ramaswamy H. Sarma.

01 Dec 2024·New Microbes and New Infections

Lymphotropic polyomavirus and Merkel cell polyomavirus in patients infected with HIV or hepatitis B or C virus

Article

Author: Abedi Kiasari, Bahman ; Hoda Fallah, Fatemeh ; Alipour, Amir Hossein ; Hemmati, Negar ; Gholamnezhad, Mohammad

BackgroundLPV and MCV emerge as recent additions to the Polyomaviridae family, capable of inducing important infections. Studies have suggested the presence of LPV in human populations, with potential involvement in central nervous system (CNS) diseases. Additionally, MCV, closely related to LPV, has been implicated in Merkel cell carcinoma (MCC). This study aimed to explore the prevalence of LPV and MCV in individuals with compromised immunity due to chronic viral infections.Methods340 specimens, including HIV PCR-positive, HBV PCR-positive, HCV PCR-positive, and HIV/HBV/HCV negative sera, underwent screening via PCR technique to identify LPV and MCV genomes. Subsequently, sequencing was employed to validate the viral identity.ResultsOut of all specimens, MCV DNA was detected in 8.52 % of participants, with a significantly higher prevalence in HIV-positive individuals (26.4 %). LPV was detected in only one HIV-positive patient. No co-detection of MCV and LPV was observed. Phylogenetic analysis confirmed the genetic similarity of the detected MCV strains to known references, while the LPV sequence showed 99 % identity to the published sequences of LPV-K38.ConclusionThis research provides insights into the prevalence of LPV and MCV in individuals with chronic viral infections. The study highlights the potential association between MCV and immunocompromised states, emphasizing the need for comprehensive investigations to understand the epidemiology, transmission routes, and clinical implications of these polyomaviruses in human populations.

3

News (Medical) associated with Lopinavir/Ritonavir

01 Nov 2022

·endpts.com

Covid-19 continues to befuddle Big Pharma as AbbVie axes PhI of an oral drug

In the fight against Covid-19, AbbVie’s approved products and investigational assets have run into multiple hurdles. The latest is a Phase I axe, quietly revealed on the federal clinical trials database in recent days. The Chicago-area Big Pharma cited “re-evaluation of risk vs benefit (based on animal data)” in an update to the Phase I trial of ABBV-990. AbbVie had hoped the drug would work as a treatment for patients with SARS-CoV-2, but it appears it won’t make it past the 24-person healthy volunteer study conducted in northern Illinois. AbbVie did not reply to emailed requests for comment. It is unclear if the asset came from the Big Pharma’s partnership with Scripps Research’s Calibr, a drug discovery and development unit funded by the Bill & Melinda Gates Foundation. Endpoints News has reached out to Scripps, which announced the collaboration in March of this year. AbbVie has made multiple attempts to find antivirals and potential treatments to ward off the worst of the pandemic but hasn’t found the right one just yet. Multiple other biopharmas have attempted creating treatments and vaccines in the global fight against the pandemic, but many have run into hurdles, largely because of the various strains that have emerged along the way. For AbbVie specifically, the company had tried to bring forth an antibody combo — out of partner Harbour BioMed and researchers at Utrecht University and Erasmus Medical Center. But the asset doesn’t appear on AbbVie’s public pipeline after a Phase I wrapped up in 2021 . The antibody still shows up on Harbour’s website, with a “global license to AbbVie” description. The National Institute of Allergy and Infectious Diseases had also previously tried combining remdesivir with AbbVie’s Skyrizi , a human monoclonal antibody approved for plaque psoriasis. Earlier in the pandemic, AbbVie had also donated supplies of the HIV medicine Kaletra/Aluvia (lopinavir/ritonavir), but the WHO stopped the portion of a trial testing the treatment for hospitalized patients in July 2020.

AntibodyVaccineLicense out/inCollaborate

25 Oct 2022

·www.biospace.com

3T Biosciences Announces Appointment of John Leonard, M.D. to its Board of Directors

Current president and CEO of Intellia Therapeutics and previous global head of Abbvie's R&D brings more than 30 years' experience leading discovery, development, and launch of groundbreaking blockbuster medicines SAN FRANCISCO, Calif., Oct. 25, 2022 /PRNewswire/ -- 3T Biosciences ("3T"), an immunotherapy company changing the future of treatment for solid tumors and other immune-mediated diseases, today announced the appointment of John Leonard, M.D. to its board of directors. Dr. Leonard is currently president and chief executive officer (CEO) of Intellia Therapeutics ("Intellia"), which he joined in 2014 at its formation. He leads the company's efforts to turn its CRISPR-based genome editing technology into a therapeutic reality. Prior to Intellia, he served as chief scientific officer and global vice president of research and development (R&D) at AbbVie. "On behalf of the entire management team at 3T Biosciences, I am thrilled to welcome John to our board of directors," said Stefan J. Scherer, M.D., Ph.D., president and CEO of 3T Biosciences. "John has decades of experience leading breakthrough medicines through their discovery, development, and launch into blockbuster drugs. Because of his work, patients around the world now have better treatments for AIDS, autoimmune disorders, and many other life-altering diseases. His leadership will be an invaluable asset to 3T." "Working with promising novel therapeutic modalities is my passion, and 3T is truly transforming the way we look at treating solid tumors and immune-mediated diseases," said Dr. Leonard. "I believe in the company's mission and science, and I'm thrilled to join 3T's board of directors." Throughout his career, Dr. Leonard has overseen the development of numerous novel therapeutics at AbbVie and, prior to that, at Abbott, where he served as senior vice president of Global R&D. His groundbreaking work with HIV protease inhibitors NORVIR® (ritonavir) and KALETRA® (lopinavir/ritonavir) led to new treatment paradigms for AIDS and his years of work with HUMIRA® (adalimumab) made it the all-time top-selling drug worldwide. His contributions led to the significant growth of the R&D pipelines at Abbott and AbbVie. Dr. Leonard serves on the boards of Intellia and IQVIA. He received his M.D. from the Johns Hopkins University School of Medicine and completed his residency in internal medicine at Stanford University, followed by a fellowship at the National Institutes of Health. About 3T Biosciences 3T Biosciences is an immunotherapy company focused on discovering and developing next-generation therapies with curative potential based on its immune-response guided target discovery approach. 3T Biosciences' 3T-TRACE platform technology is designed to overcome the challenges of advancing T-cell receptor (TCR)-based therapeutics. Based in South San Francisco, 3T Biosciences is led by an experienced management team and supported by top investors including Westlake Village BioPartners, Lightspeed Venture Partners, and the Parker Institute for Cancer Immunotherapy. For more information, please visit .

Gene TherapyImmunotherapy

29 Nov 2012

·www.pharmatimes.com

Abbott chiefs OK AbbVie split, declare dividend

Abbott's Board of Directors has given the thumbs up for cleaving off its research arm, and has also declared a special dividend distributing the outstanding shares of the new firm's common stock. The company first announced in October 2011 that it would be spinning off its research-based pharmaceuticals business into a separate entity called AbbVie. Now, just a step away from completing the separation, Abbott's board has announced that for every one share of Abbott common shares held, shareholders will receive one share of AbbVie common stock. No fractional shares of AbbVie will be issued, with shareholders to receive cash for these instead, it said. The distribution of AbbVie common stock will finalise the split, establishing AbbVie as a research-based specialty biopharmaceuticals company with a broad portfolio of medicines. The newborn's chief asset will be the blockbuster Humira (adalimumab), followed by the prostate cancer drug Lupron (leuprolide), the HIV therapy Kaletra (lopinavir/ritonavir) and the hypothyroid medication Synthroid (levothyroxine). Abbott, on the other hand, will be one of the largest science-based healthcare companies with offerings in diagnostics, medical devices, nutritionals and branded generic pharmaceuticals – "all aligned with favourable healthcare trends", the firm noted.

100 Deals associated with Lopinavir/Ritonavir

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External Link

KEGG	Wiki	ATC	Drug Bank
-	Lopinavir/Ritonavir	J05AR10	-

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
HIV Infections	US	AbbVie, Inc.	15 Sep 2000

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hepatitis C	Phase 2	-	Abbott Laboratories	21 Jul 2005
COVID-19	Phase 2	-	-	-
Human Papillomavirus Infection	IND Application	-	Daré Bioscience, Inc.	01 Nov 2024
Coinfection	Discovery	CA	Abbott Laboratories	01 Jun 2007
Hepatitis C	Discovery	-	Abbott Laboratories	21 Jul 2005
HIV Infections	Discovery	-	Abbott Laboratories	01 Aug 2003

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04372628 (Pubmed)	Phase 2	COVID-19	448	Lopinavir/ritonavir	(nniwmgchav) = gswcnicutg unhudxuneq (yghrusngst )	Negative	26 Dec 2022
				Placebo	(nniwmgchav) = bffzfvnbhr unhudxuneq (yghrusngst )
NCT04499677 (Pubmed)	Phase 2	COVID-19	240	Favipiravir+Lopinavir-Ritonavir	(cplucygouf) = ijxzjuutim igjmmadmuf (rberzteirv, -1.21 to 0.07)	Negative	19 Oct 2022
				Favipiravir+Placebo	tqjtqkokgs(zkbkqvislv) = cvdrshmfpb ncsfcdenhu (vsguokxvgp )
NCT04354428 (CTgov)	Phase 2/3	COVID-19	289	Ascorbic Acid+Folic Acid (Ascorbic Acid and Folic Acid)	hesicbmytw(fozxjiuqbu) = mkjeytdmel ztwhbazcjp (ogmdspgigi, seqnzevbbl - wsawcmrzbk) View more	-	08 Aug 2022
				Hydroxychloroquine Sulfate+Folic Acid (Hydroxychloroquine and Folic Acid)	hesicbmytw(fozxjiuqbu) = uwinfqhsrm ztwhbazcjp (ogmdspgigi, pkenohaldn - wkxghqmnwl) View more
NCT02369965 (TALENT, NEWS) Manual	Phase 3	HIV Infections	418	Lopinavir/Ritonavir+艾可宁	qddaxyuipr(euxjfmyiun) = gnaorfxxim lgqlnlyxbn (lwcpaqogum )	Non-inferior	13 Jun 2022
				Lopinavir/Ritonavir+NRTI	qddaxyuipr(euxjfmyiun) = hsncnypkze lgqlnlyxbn (lwcpaqogum )
NCT04425382 (DOLCI, Pubmed)	Not Applicable	COVID-19	400	Darunavir-cobicistat	(jppbdqhydz) = chnacrhzac qjdctopqkf (fqepgbkvrd, 4 - 13) View more	Negative	01 Jan 2022
				Lopinavir-ritonavir	(jppbdqhydz) = sptqpmtryr qjdctopqkf (fqepgbkvrd, 3 - 8) View more
NCT04364022 (COPEP, Pubmed)	Phase 3	COVID-19	318	Lopinavir/Ritonavir PEP	pkywmlramx(cnsgvquytc): unadjusted hazard ratio = 1.44 (95% CI, 0.76 - 2.73), P-Value = 0.18; P-Value = 0.60	-	01 Dec 2021
				Lopinavir-Ritonavir (Surveillance)
NCT01632891 (A5297, Pubmed \| J Acquir Immune Defic Syndr)	Phase 1/2	HIV Infections	52	Lopinavir/ritonavir-based ART	hfijctlggc(mcryhdpbjp) = tjcroohsxv ijumhegytq (grlgwvsuwv )	-	19 Oct 2021
				non-nucleoside reverse transcriptase inhibitor-based ART	hfijctlggc(mcryhdpbjp) = vxeoxcolzo ijumhegytq (grlgwvsuwv )
NCT01818258 (IMPAACT P1092, CTgov)	Phase 4	Malnutrition \| HIV Seropositivity	52	Zidovudine+Lamivudine+Lopinavir/Ritonavir (Severe Malnutrition)	nzzaikzlxq(bqclvcybya) = vbxyykhddm ptycyozfux (gbknmbmwob, bvvbqsiqkb - bxjtstdyyi) View more	-	12 Aug 2021
				Zidovudine+Lamivudine+Lopinavir/Ritonavir (Normal Nutrition/Mild Malnutrition)	nzzaikzlxq(bqclvcybya) = bdgmnmmecx ptycyozfux (gbknmbmwob, aaxlpmbgdo - momlcnamov) View more
NCT02735707 (REMAP-CAP, Pubmed \| Intensive Care Med)	Phase 3	COVID-19	694	Lopinavir-ritonavir	(xpvezylggo) = dalalexnhh lhvsceytdu (xawwdxjcyl )	Negative	01 Aug 2021
				Hydroxychloroquine	(xpvezylggo) = etztefosps lhvsceytdu (xawwdxjcyl )
IAS2021	Not Applicable	-	-	lopinavir/ritonavir granules (Pouring directly into the child's tongue)	fvcshjakzi(uvmrfmwgrq) = ccnrwmbcst acfmwyicso (rrrsujyqol )	-	01 Jan 2021