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27 results for “drug resistance mutations”

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dryad36/100

PfCRT mutations conferring piperaquine resistance in falciparum malaria shape the kinetics of quinoline drug binding and transport

<p>These data were generated to investigate the effect of point mutations in PfCRT on the kinetics of chloroquine and piperaquine binding and transport. The protein confers resistance to a range of quinoline and quinoline-like antimalarials after the acquisition of certain amino acid substitutions, which occurs as a result of improper antimalarial use. The change in prescription from chloroquine (CQ) to piperaquine (PPQ) in Southeast Asian countries led to the emergence of a ninth mutation over the PfCRT Dd2 isoform, which renders the parasites resistant to piperaquine but re-sensitizes them to chloroquine. Despite structural information, how these individual mutations influence such opposing changes in the parasite's susceptibility to the aforementioned drugs remains unknown. Here, we show by biochemical studies that any of the piperaquine resistance-conferring mutations H97Y, F145I, M343L or G353V, either reduce the affinity of PfCRT Dd2 for CQ (Km) or reduce the efficiency of the transport cycle (Vmax). In parallel, they increase the Vmax, reduce the Km, or do both, in the case of PPQ transport. We also probed the binding cavity of PfCRT Dd2 and that of PfCRT Dd2_F145I, and found that it can readily bind both CQ and PPQ simultaneously, in a partial noncompetitive mechanism. We confirmed the latter finding through molecular docking and molecular dynamics simulations, describing for the first time the binding sites for both drugs in the cavity of PfCRT Dd2. With this, we found that the pocket where CQ binds seems to require an aromatic side chain, which is normally provided by F145, or by Y97 in the PPQ resistance-conferring H97Y mutant. Lastly, we generated an unnatural double mutant carrying both the H97Y and the F145I mutations. The engineered transporter displayed non-Michaelis-Menten kinetics both for CQ and PPQ transport and instead revealed sigmoidal kinetics, typical of proteins that bind substrate cooperatively. We thus provide new insights into the organization of the substrate-binding cavity of PfCRT and into the evolution of PfCRT.</p>

opencc-zeroMay 2023View details →
ClinicalTrials.gov36/100

Reducing the Incidence of Nevirapine Resistance Mutations in Pregnant HIV Infected Women Who Receive Anti-HIV Drugs Prior to and After Giving Birth

ClinicalTrials.gov study NCT00109590. IPD Sharing: Not stated. Countries: 1. Publications: 6.

restrictedIPD-UNDECIDEDFeb 2026View details →
dryad36/100

PfCRT mutations conferring piperaquine resistance in falciparum malaria shape the kinetics of quinoline drug binding and transport

Open the record for dataset details and reuse information.

publicMay 2023View details →
ClinicalTrials.gov32/100

Primary and Secondary Drug Resistance Mutations (DRMs) in HIV As a Risk Factor of Failure of ART, Including Two Drugs Based Regimens.

ClinicalTrials.gov study NCT06661317. IPD Sharing: NO. Countries: 1. Publications: 12.

closedIPD-NOFeb 2026View details →
ClinicalTrials.gov28/100

Testing the Sequential Combination of the Anti-cancer Drugs Olaparib Followed by Adavosertib (AZD1775) in Patients With Advanced Solid Tumors With Selected Mutations and PARP Resistance, STAR Study

ClinicalTrials.gov study NCT04197713. IPD Sharing: YES. Countries: 1. Publications: 0.

controlledIPD-YESFeb 2026View details →
ClinicalTrials.gov28/100

The Influence of Primary HIV-1 Drug Resistance Mutations on Immune Reconstruction in PLWH

ClinicalTrials.gov study NCT06044792. IPD Sharing: NO. Countries: 0. Publications: 9.

closedIPD-NOFeb 2026View details →
geo24/100

Piperaquine-resistant PfCRT mutations differentially impact drug transport, hemoglobin catabolism and parasite physiology in Plasmodium falciparum asexual blood stages

GEO Series GSE205515. Plasmodium falciparum. 13 samples. Type: Expression profiling by array.

openGEO-OpenOct 2022View details →
geo24/100

Lentiviral-based mutagenesis to identify mutations that confer resistance to anti-cancer drugs

GEO Series GSE164664. Homo sapiens. 145 samples. Type: Other; Expression profiling by high throughput sequencing.

openGEO-OpenJul 2021View details →
geo24/100

The NSD2 p.E1099K Mutation is Enriched at Relapse and Confers Drug Resistance in a Cell Context Dependent Manner in Pediatric Acute Lymphoblastic Leukemia

GEO Series GSE149159. Homo sapiens. 83 samples. Type: Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing.

openGEO-OpenApr 2020View details →
geo24/100

Lentiviral-driven discovery of cancer drug resistance mutations

GEO Series GSE180965. Homo sapiens. 120 samples. Type: Expression profiling by high throughput sequencing.

openGEO-OpenJul 2021View details →
geo24/100

Evolution of drug resistance in cancer cells involves generation of numerous mutations in non-coding genome that reduces the chances of DNA breaks

GEO Series GSE189366. Homo sapiens. 8 samples. Type: Expression profiling by high throughput sequencing.

openGEO-OpenNov 2021View details →
geo24/100

Lentiviral-based mutagenesis to identify mutations that confer resistance to anti-cancer drugs [lenti]

GEO Series GSE164663. Homo sapiens. 23 samples. Type: Other.

openGEO-OpenJul 2021View details →
geo24/100

Identification of drug- resistance mutations in majority and minority subpopulations of HIV-1 quasispecies

GEO Series GSE90621. Simian-Human immunodeficiency virus. 470 samples. Type: Genome variation profiling by array.

openGEO-OpenNov 2016View details →
geo24/100

Breast cancer mutations HER2V777L and PIK3CAH1047R activate the p21-CDK4/6 –Cyclin D1 axis driving tumorigenesis and drug resistance.

GEO Series GSE216871. Mus musculus. 16 samples. Type: Expression profiling by high throughput sequencing.

openGEO-OpenJul 2023View details →
geo24/100

The NSD2 p.E1099K Mutation is Enriched at Relapse and Confers Drug Resistance in a Cell Context Dependent Manner in Pediatric Acute Lymphoblastic Leukemia (RNA-Seq)

GEO Series GSE149158. Homo sapiens. 42 samples. Type: Expression profiling by high throughput sequencing.

openGEO-OpenApr 2020View details →
geo24/100

Lentiviral-based mutagenesis to identify mutations that confer resistance to anti-cancer drugs [umi]

GEO Series GSE164661. Homo sapiens. 2 samples. Type: Other.

openGEO-OpenJul 2021View details →
geo24/100

Single-cell transcriptomics of NRAS-mutated melanoma transitioning to drug resistance: elevated P2RX7 levels indicate response to targeted therapy

GEO Series GSE230538. Homo sapiens. 16 samples. Type: Expression profiling by high throughput sequencing.

openGEO-OpenApr 2023View details →
ClinicalTrials.gov24/100

Testing the Safety and Efficacy of Commercial Drug Biktarvy in Subjects Known to Have the 184 Resistance Mutation to a Component in Biktarvy

ClinicalTrials.gov study NCT04040075. IPD Sharing: NO. Countries: 1. Publications: 0.

closedIPD-NOFeb 2026View details →
ClinicalTrials.gov24/100

Molecular Characteristics of Hepatitis B Virus Integration, Mutation, and Drug Resistance

ClinicalTrials.gov study NCT06779864. IPD Sharing: NO. Countries: 1. Publications: 0.

closedIPD-NOFeb 2026View details →
ClinicalTrials.gov24/100

Dynamics of Drug Resistance-associated Mutations in HIV-1 DNA Reverse Transcriptase Clearance During Effective Antiretroviral Therapy

ClinicalTrials.gov study NCT04448158. IPD Sharing: NO. Countries: 1. Publications: 0.

closedIPD-NOFeb 2026View details →

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International Brain Laboratory public data

The International Brain Laboratory public data releases expose standardized mouse decision-making experiments, including Neuropixels recordings, widefield calcium imaging, behavior, and session metadata accessed through the ONE API.

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Last verified 2026-04-29Open record

OpenNeuro

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Last verified 2026-04-29Open record