Evidence map›Paper›PMID 31619389›Full record

ArticleDrug metabolism and disposition: the biological fate of chemicals2019

Brain Distributional Kinetics of a Novel MDM2 Inhibitor SAR405838: Implications for Use in Brain Tumor Therapy.

Minjee Kim, Janice K Laramy, Gautham Gampa, Karen E Parrish, Richard Brundage, Jann N Sarkaria, William F Elmquist

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Drug metabolism and disposition: the biological fate of chemicals, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.0field-weighted citation impact, top 22% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 15 citations in OpenAlex.

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  8. Understanding the brain uptake and permeability of small molecules through the BBB: A technical overview.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Minjee KimBrain Barriers Research Center, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota (M.K., J.K.L., G.G., K.E.P., W.F.E.); Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, Minnesota (R.B.); and Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.).
Janice K LaramyBrain Barriers Research Center, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota (M.K., J.K.L., G.G., K.E.P., W.F.E.); Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, Minnesota (R.B.); and Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.).
Gautham GampaBrain Barriers Research Center, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota (M.K., J.K.L., G.G., K.E.P., W.F.E.); Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, Minnesota (R.B.); and Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.).
Karen E ParrishBrain Barriers Research Center, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota (M.K., J.K.L., G.G., K.E.P., W.F.E.); Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, Minnesota (R.B.); and Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.).
Richard BrundageBrain Barriers Research Center, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota (M.K., J.K.L., G.G., K.E.P., W.F.E.); Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, Minnesota (R.B.); and Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.).
Jann N SarkariaBrain Barriers Research Center, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota (M.K., J.K.L., G.G., K.E.P., W.F.E.); Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, Minnesota (R.B.); and Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.).
William F ElmquistBrain Barriers Research Center, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota (M.K., J.K.L., G.G., K.E.P., W.F.E.); Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, Minnesota (R.B.); and Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.) elmqu011@umn.edu.
Mayo Clinic · USUniversity of Minnesota · US

Funding

Transport Oncophysics CoreU54CA210181 · NCI · METHODIST HOSPITAL RESEARCH INSTITUTE · PI WANG, RONGFU · 2016 to 2020
$9.3M
Pre-Clinical Novel Radiosensitizer Evaluation Program for Brain TumorsU01CA227954 · NCI · MAYO CLINIC ROCHESTER · PI SARKARIA, JANN N. · 2018 to 2022
$3.0M
Influence of Anti-Angiogenic Therapy on Drug Delivery to Brain TumorsR01NS077921 · NINDS · UNIVERSITY OF MINNESOTA · PI ELMQUIST, WILLIAM, SARKARIA, JANN N. · 2012 to 2016
$2.5M
Improving Delivery of Molecularly-Targeted Therapy to Invasive Glioma CellsR01CA138437 · NCI · UNIVERSITY OF MINNESOTA · PI ELMQUIST, WILLIAM, OHLFEST, JOHN R · 2010 to 2014
$1.5M
NCI NIH HHS R01 CA138437NCI NIH HHS U01 CA227954NCI NIH HHS U54 CA210181NINDS NIH HHS R01 NS077921
6 · The paper itself

Abstract

Achieving an effective drug concentration in the brain is as important as targeting the right pathway when developing targeted agents for brain tumors. SAR405838 is a novel molecularly targeted agent that is in clinical trials for various solid tumors. Its application for tumors in the brain has not yet been examined, even though the target, the MDM2-p53 interaction, is attractive for tumors that could occur in the brain, including glioblastoma and brain metastases. In vitro and in vivo studies indicate that SAR405838 is a substrate of P-glycoprotein (P-gp). P-gp mediated active efflux at the blood-brain barrier plays a dominant role in limiting SAR405838 brain distribution. Even though the absence of P-gp significantly increases the drug exposure in the brain, the systemic exposure, including absorption and clearance processes, were unaffected by P-gp deletion. Model-based parameters of SAR405838 distribution across the blood-brain barrier indicate the CL

Indexed as

Models, BiologicalAnimalsATP Binding Cassette Transporter, Subfamily B, Member 1ATP Binding Cassette Transporter, Subfamily G, Member 2Biological TransportBlood-Air BarrierBrainBrain NeoplasmsDogsHumansIndolesMadin Darby Canine Kidney CellsMice, TransgenicNeoplasm ProteinsProto-Oncogene Proteins c-mdm2Spiro CompoundsABCG2 protein, humanATP Binding Cassette Transporter, Subfamily B, Member 1ATP Binding Cassette Transporter, Subfamily G, Member 2IndolesNeoplasm ProteinsProto-Oncogene Proteins c-mdm2SAR405838Spiro CompoundsTumor Suppressor Protein p53

Identifiers

PMID31619389
PMCPMC7042719
OpenAlexW2980414139

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.