ritonavir

P2, N=180, Active, not recruiting, Karolinska Institutet | Recruiting --> Active, not recruiting | N=400 --> 180 | Trial completion date: Mar 2024 --> Nov 2024 | Trial primary completion date: Jan 2024 --> Nov 2024

P1, N=60, Terminated, University of Chicago | N=100 --> 60 | Trial completion date: Apr 2025 --> Aug 2024 | Recruiting --> Terminated | Trial primary completion date: Apr 2025 --> Aug 2024; Terminated by the PI

P4, N=350, Recruiting, Gilead Sciences | Not yet recruiting --> Recruiting

P1/2, N=766, Recruiting, DualityBio Inc. | Trial completion date: Oct 2025 --> Oct 2027 | Trial primary completion date: Jun 2025 --> Apr 2026

Interestingly, we observed that one of the inhibitors, ritonavir, could inhibit ALKBH2-mediated DNA repair significantly via competitive inhibition and sensitized cancer cells to alkylating agent methylmethane sulfonate (MMS). This work may provide new insights into the possibilities of utilizing HIV protease inhibitor ritonavir as a DNA repair antagonist.

P2, N=250, Completed, Sunshine Lake Pharma Co., Ltd. | Recruiting --> Completed | Trial completion date: May 2023 --> Sep 2023

P1, N=24, Terminated, The Netherlands Cancer Institute | Unknown status --> Terminated; low inclusion of patients and availability of the IP

P1, N=24, Not yet recruiting, University of Miami

P2, N=0, Withdrawn, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | N=30 --> 0 | Trial completion date: Oct 2028 --> May 2024 | Not yet recruiting --> Withdrawn | Trial primary completion date: Oct 2027 --> May 2024

Momelotinib-approved for treatment of myelofibrosis in adults with anemia-and its major active metabolite, M21, were assessed as drug-drug interaction (DDI) victims with a strong cytochrome P450 (CYP) 3A4 inhibitor (multiple-dose ritonavir), an organic anion transporting polypeptide (OATP) 1B1/1B3 inhibitor (single-dose rifampin), and a strong CYP3A4 inducer (multiple-dose rifampin). Momelotinib DDI perpetrator potential (multiple-dose) was evaluated with CYP3A4 and breast cancer resistance protein (BCRP) substrates (midazolam and rosuvastatin, respectively)...Safety findings were mild in this short-term study in healthy volunteers. This analysis suggests that momelotinib interactions with OATP1B1/1B3 inhibitors and BCRP substrates may warrant monitoring for adverse reactions or dose adjustments.

P4, N=350, Not yet recruiting, Gilead Sciences

P3, N=170, Completed, The HIV Netherlands Australia Thailand Research Collaboration | Active, not recruiting --> Completed | Trial completion date: Dec 2022 --> Apr 2023 | Trial primary completion date: Dec 2022 --> Apr 2023

Both parental and resistant cell lines were treated with the taxane drugs docetaxel and cabazitaxel in combination with the P-gp/CYP3A4 inhibitor ritonavir and the P-gp inhibitor elacridar. In a Caco-2 P-gp transporter assay, functional inhibition of P-gp-mediated transport of docetaxel with ritonavir was demonstrated. Our results demonstrate that ritonavir restores sensitivity to both docetaxel and cabazitaxel in docetaxel-resistant cell lines, most likely by inhibiting P-gp-mediated drug efflux.

P1, N=122, Completed, National Institute of Neurological Disorders and Stroke (NINDS) | Active, not recruiting --> Completed | Trial completion date: Oct 2024 --> May 2023 | Active, not recruiting --> Completed

P1, N=40, Completed, Daiichi Sankyo Co., Ltd. | Active, not recruiting --> Completed | Trial completion date: Mar 2024 --> Sep 2023

Covariates previously detected to be statistically significant (cancer type, tumor size, albumin, race-country, body weight and sex for T-DXd; age, cancer type, AST, total bilirubin, ritonavir or itraconazole use, race-country, formulation and body weight for DXd) were retained in the PopPK model. Similar T-DXd and DXd exposures were obtained for the recommended dosing of 5.4 mg/kg Q3W T-DXd in BC subjects across categories of hepatic function, renal function, region, race-country, HER2 status, and line of therapy.

P1/2, N=631, Recruiting, DualityBio Inc. | N=463 --> 631

P2, N=59, Completed, ViiV Healthcare | Unknown status --> Completed

P1, N=40, Active, not recruiting, Daiichi Sankyo Co., Ltd. | Trial completion date: Sep 2023 --> Mar 2024

For additional docking investigations with distinct proteins, the leaf chemicals are assessed, that is, the crystal structure of serine protease hepsin in complex with inhibitor [PDB ID:5 CE1] for antiviral activity human topoisomerase II beta in complex with DNA and etoposide [PDB ID:3QX3] and crystal structure of E. coli GyraseB 24 kDa in complex with 4-(4-bromo-1H-pyrazol-1-yl)-6-[(ethylcarbamoyl)amino]-N-(pyridin-3-yl) pyridine-3-carboxamide [PDB ID: 6F86] for antibacterial activity and have been selected. To evaluate the in silico results and grading of virtual screening, or molecular docking, ritonavir antiviral activity and ampicillin for antibacterial activity were used as a benchmark.

Cabozantinib as a single agent should be initiated at 20 mg daily and 60 mg daily when taken concurrently with ARVs that are strong CYP3A4 inhibitors and inducers, respectively, with consideration for subsequent escalation per current cabozantinib guidelines.

Lamivudine plus Zidovudine and Lopinavir plus Ritonavir were given as antiretroviral medications. Compliance in antiretroviral therapy is significant and effective in the control of the disease. Extensive mucocutaneous involvement requires palliative and multispecialty management

Patients under treatment with rituximab or BTK-inhibitors have lower antibody responses against SARS-CoV-2; thus, they should continue to follow preventive measures, including mask wearing and avoiding crowded places...Coadministration of ibrutinib or venetoclax with ritonavir should be avoided. In these patients, remdesivir offers an effective alternative. Patients with asymptomatic or oligosymptomatic COVID-19 should not interrupt treatment with a BTK inhibitor. Infection prophylaxis is essential in patients with WM and include general preventive measures, prophylaxis with antivirals and vaccination against common pathogens including SARS-CoV-2, influenza, and S. pneumoniae.

P1, N=40, Active, not recruiting, Daiichi Sankyo Co., Ltd. | Trial completion date: Mar 2023 --> Sep 2023

This study suggests that immunogenetically manipulated mice with deletion of IL-10 may have reduced capacity to contain MMTV infection in a mouse-strain-specific manner, and the antiviral inflammatory responses may contribute to the complexity of IBD with the development of colitis and dysbiosis. Video Abstract.

Consistent with observations from clinical studies, our data provide direct evidence that activated variants of the PLCγ1 enzyme contribute to the properties of the malignant T-cell clone in ATL.

We also found that HNF4A agonist (Benfluorex) and GLUT4 inhibitor (antiviral drug Ritonavir) can suppress HCC cell proliferation and glucose uptake. Taken together, these results all suggest that activation of the AMPKα2/HNF4A/BORIS/GLUT4 signaling pathway in a low-glucose microenvironment can significantly promote the invasion and metastasis of HCC cells, while HNF4A and GLUT4 may have important potential applications as prognostic or drug target molecules.

These observations suggest that anti-viral compound (RTV) could act synergistically with Cisplatin for cervical cancer therapy. However, further studies are warranted to investigate the combinatorial mode of action of RTV and Cisplatin on different molecular pathways to have a translational outcome in cervical cancer.Communicated by Ramaswamy H. Sarma.

Synergistic activity was observed when PYR was combined with Doxorubicin and Ritonavir. Thus, our study demonstrates for the first time that PYR can be repurposed against GBM with a novel mechanism of action involving Par-4. Herewith, we discuss the role of upregulated Par-4 in a highly interconnected signaling network thereby advocating its importance as a therapeutic target.

The derivative of protease inhibitor ritonavir (5-methyl-4-oxohexanoic acid ritonavir ester; RD) was recently recognized as a potent P-gp inhibitor and cancerostatic drug inhibiting the proteasome and STAT3 signaling. Star-RD + Dox efficiently inhibited STAT3 signaling and induced caspase-3 activation and DNA fragmentation in cancer cells in vivo. Importantly, Star-RD + Dox was found to have superior antitumor activity in terms of tumor growth inhibition and increased survival of mice bearing P-gp-expressing tumors.

Ritonavir (RTV), a pharmacoenhancer used in anti-HIV regimens, can induce liver damage. Increased susceptibility to RTV-induced liver injury caused by the PXR activator rifampicin was attenuated by HNF4A-AS1 overexpression or HNF1A-AS1 knockdown. Taken together, these results revealed that HNF4A-AS1 and HNF1A-AS1 modulated RTV-induced hepatotoxicity by regulating CYP3A4 expression, primarily by affecting the binding of PXR and histone modification status in the CYP3A4 promoter.

Using molecular dynamics simulation, we elucidated the molecular details of Ritonavir-ALKBH2 interaction. The present work highlights that Ritonavir might be used to target the ALKBH2-mediated DNA alkylation repair.

Full doses of PCb chemotherapy are tolerable when given concurrently with ART in people living with human immunodeficiency virus with cancer, including patients receiving CYP3A4 inhibitors.

P1, N=40, Active, not recruiting, Daiichi Sankyo Co., Ltd. | Trial completion date: Mar 2022 --> Mar 2023

Furthermore, FDA-approved retroviral protease inhibitors ritonavir, atazanavir, and lopinavir reduced proliferation of schwannoma and grade I meningioma cells. Furthermore, FDA-approved retroviral protease inhibitors ritonavir, atazanavir, and lopinavir reduced proliferation of schwannoma and grade I meningioma cells. These results identify HERV-K as a critical regulator of progression in Merlin-deficient tumours and offer potential strategies for therapeutic intervention.

Ritonavir (RTV), a pharmacoenhancer used in anti-HIV regimens, can induce liver damage. Significance Statement HNF4A-AS1 and HNF1A-AS1, transcribed separately from neighboring antisense genes of the human transcription factor genes HNF4A and HNF1A, were identified as lncRNAs that can affect RTV-induced hepatotoxicity and susceptibility to RTV-induced hepatotoxicity caused by rifampicin exposure, mainly by affecting the expression of CY3A4 via alterations in PXR enrichment and histone modification status in the CYP3A4 promoter. This discovery provides directions for further research on the mechanisms of RTV-induced liver injury.

Ritonavir enhances the ability of RTS-V5 to cause ER stress in bladder cancer cells.

T-DXd was safely combined with ritonavir or itraconazole without clinically meaningful impact on T-DXd or DXd pharmacokinetics.

Five Ru(II)-based derivatives were prepared from two analogs of the CYP3A4 inhibitor ritonavir, 4 and 6: [Ru(tpy)(L)(6)]Cl (tpy = 2,2':6',2″-terpyridine) with L = 6,6'-dimethyl-2,2'-bipyridine (Mebpy; 8), dimethylbenzo[i]dipyrido[3,2-a:2',3'-c]phenazine (Medppn; 10) and 3,6-dimethyl-10,15-diphenylbenzo[i]dipyrido[3,2-a:2',3'-c]phenazine (MePhdppn; 11), [Ru(tpy)(Mebpy)(4)]Cl (7) and [Ru(tpy)(Medppn)(4)]Cl (9). In prostate adenocarcinoma DU-145 cells, compound 9 had the best synergistic effect with vinblastine, the anticancer drug primarily metabolized by CYP3A4 in vivo. Thus, our study establishes a new paradigm in CYP inhibition using metalated complexes and suggests possible utilization of photoactive CYP3A4 inhibitory compounds in clinical applications, such as enhancement of therapeutic efficacy of anticancer drugs.

In a drug-drug-interaction study in healthy human participants, liver enzyme elevations were observed when a single 100 mg dose of lorlatinib was administered after multiple doses of rifampin, a strong cytochrome P450 (CYP) 3 A inducer and a pregnane X receptor (PXR) agonist...John's wort) or predominantly constitutive androstane receptor (CAR) agonists (carbamazepine, phenytoin) and a net CYP3A inhibitory PXR agonist (ritonavir)...Furthermore, liver toxicity was only observed in this model when lorlatinib was co-administered with strong CYP3A inducers, and the effects were not restricted to, or exclusively dependent upon, a PXR activation mechanism. These results generated mechanistic insights on the liver enzyme elevations observed in the clinical drug-drug interaction study and provided guidance on appropriate product safety label for lorlatinib.

iii) FDA-approved retroviral protease inhibitors Ritonavir, Atazanavir and Lopinavir decreased pERK1/2 and cyclin D1 and reduced proliferation of schwannoma and grade I meningioma cells.We provide evidence for HERV-K Env contributing to the development of NF2-associated schwannomas and meningiomas. Considering the urgent need of drugs to treat NF2, we suggest the trialling of antiretroviral protease inhibitors, and consideration of anti-HERV-K Env immunotherapy, as well as TEAD-specific inhibitors in these patients. The above treatments would also be potentially beneficial for patients with other tumors caused by Merlin deficiency.