Evidence map›Paper›PMID 36123502›Full record

ArticleThe AAPS journal2022

Sinusoidal Organic Anion-Transporting Polypeptide 1B1/1B3 and Bile Canalicular Multidrug Resistance-Associated Protein 2 Play an Essential Role in the Hepatobiliary Disposition of a Synthetic Cyclic Dinucleotide (STING Agonist).

Philip Sandoval, Bei-Ching Chuang, John K Fallon, Philip C Smith, Swapan K Chowdhury, Robert J Griffin, Cindy Q Xia, Shinji Iwasaki, Paresh P Chothe

Open access · hybridAbstract read
PubMed Publisher
In one paragraph

Article in The AAPS journal, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.3field-weighted citation impact, top 41% 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

1 citing paper in PubMed, 2 citations in OpenAlex.

  1. Article
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

9 authors at 5 institutions in 2 countries.

Philip SandovalGlobal Drug Metabolism and Pharmacokinetics, Takeda Development Center Americas, Inc. (TDCA), 95 Hayden Avenue, Lexington, Massachusetts, 02421, USA.
Bei-Ching ChuangGlobal Drug Metabolism and Pharmacokinetics, Takeda Development Center Americas, Inc. (TDCA), 95 Hayden Avenue, Lexington, Massachusetts, 02421, USA.
John K FallonDivision of Pharmacoengineering and Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Philip C SmithDivision of Pharmacoengineering and Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Swapan K ChowdhuryBoston Pharmaceuticals, 55 Cambridge Parkway, Suite 400, Cambridge, Massachusetts, 02142, USA.
Robert J GriffinGlobal Drug Metabolism and Pharmacokinetics, Takeda Development Center Americas, Inc. (TDCA), 95 Hayden Avenue, Lexington, Massachusetts, 02421, USA.
Cindy Q XiaReNAgade Therapeutics Management Co., 450 Kendall Street, Cambridge, Massachusetts, 02142, USA.
Shinji IwasakiDrug Metabolism and Pharmacokinetics Research Laboratories, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-Higashi 2-Chrome, Fujisawa, Kanagawa, 251-8555, Japan.
Paresh P ChotheGlobal Drug Metabolism and Pharmacokinetics, Takeda Development Center Americas, Inc. (TDCA), 95 Hayden Avenue, Lexington, Massachusetts, 02421, USA. pareshchothe@yahoo.com.ORCID 0000-0001-5661-9011
Takeda (United States) · USUniversity of North Carolina at Chapel Hill · USAVEO Oncology (United States) · USCenter for Global Development · USTakeda (Japan) · JP

Funding

Shared UPLC-MS/MS for Absolute Quantitative ProteomicsS10RR024595 · NCRR · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SMITH, PHILIP C · 2008 to 2008
$381k
NCRR NIH HHS S10 RR024595
6 · The paper itself

Abstract

The liver is central to the elimination of many drugs from the body involving multiple processes and understanding of these processes is important to quantitively assess hepatic clearance of drugs. The synthetic STING (STimulator of INterferon Genes protein) agonist is a new class of drugs currently being evaluated in clinical trials as a potential anticancer therapy. In this study, we used ML00960317 (synthetic STING agonist) to investigate the hepatobiliary disposition of this novel molecular entity. A bile-duct cannulated (BDC) rat study indicated that biliary excretion is the major route of elimination for ML00960317 (84% of parent dose in bile). The human biliary clearance using in vitro sandwich cultured human hepatocyte model predicted significant biliary excretion of ML00960317 (biliary excretion index (BEI) of 47%). Moreover, the transport studies using transporter expressing cell lines, hepatocytes, and membrane vesicles indicated that ML00960317 is a robust substrate of OATP1B1, OATP1B3, and MRP2. Using relative expression factor approach, the combined contribution of OATP1B1 (fraction transported (f

Indexed as

BileOrganic Anion TransportersAnimalsAnionsHumansInterferonsLiver-Specific Organic Anion Transporter 1Multidrug Resistance-Associated Protein 2PeptidesRatsRifampinSolute Carrier Organic Anion Transporter Family Member 1B3AnionsInterferonsLiver-Specific Organic Anion Transporter 1Multidrug Resistance-Associated Protein 2Organic Anion TransportersPeptidesRifampinSolute Carrier Organic Anion Transporter Family Member 1B3cyclic dinucleotidedrug-drug interactionhepatobiliary dispositionMRP2OATPs

Identifiers

PMID36123502
OpenAlexW4296458239

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.