Evidence map›Paper›PMID 39353935›Full record

ArticleNature communications2024

Sol-moiety: Discovery of a water-soluble prodrug technology for enhanced oral bioavailability of insoluble therapeutics.

Arvin B Karbasi, Jaden D Barfuss, Theodore C Morgan, Daniel Collins, Drew A Costenbader, David G Dennis, Andrew Hinman, KyuWeon Ko, Cynthia Messina, Khanh C Nguyen and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
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

5 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Bridging bioactive metabolites ofFrontiers in pharmacology · 2026
    Review
  5. 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

16 authors.

Arvin B KarbasiSarafan ChEM-H, Stanford University, Stanford, CA, 94305, USA.ORCID 0000-0001-6096-9647
Jaden D Barfuss *Sarafan ChEM-H, Stanford University, Stanford, CA, 94305, USA.ORCID 0000-0001-9167-3793
Theodore C Morgan *Sarafan ChEM-H, Stanford University, Stanford, CA, 94305, USA.ORCID 0009-0008-1072-1131
Daniel CollinsSarafan ChEM-H, Stanford University, Stanford, CA, 94305, USA.
Drew A CostenbaderSarafan ChEM-H, Stanford University, Stanford, CA, 94305, USA.
David G DennisSarafan ChEM-H, Stanford University, Stanford, CA, 94305, USA.
Andrew HinmanSarafan ChEM-H, Stanford University, Stanford, CA, 94305, USA.
KyuWeon KoSarafan ChEM-H, Stanford University, Stanford, CA, 94305, USA.
Cynthia MessinaSarafan ChEM-H, Stanford University, Stanford, CA, 94305, USA.
Khanh C NguyenDivision of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Rebecca C SchugarDivision of Endocrinology, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Karin A SteinSarafan ChEM-H, Stanford University, Stanford, CA, 94305, USA.
Brianna B WilliamsSarafan ChEM-H, Stanford University, Stanford, CA, 94305, USA.
Haixia XuDivision of Endocrinology, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Justin P AnnesDivision of Endocrinology, Stanford University School of Medicine, Stanford, CA, 94305, USA.ORCID 0000-0001-8431-3589
Mark SmithSarafan ChEM-H, Stanford University, Stanford, CA, 94305, USA. mxsmith@stanford.edu.ORCID 0000-0002-0313-5723

Funding

The Role of Adenosine Kinase in Controlling Beta-Cell RegenerationR01DK101530 · NIDDK · STANFORD UNIVERSITY · PI ANNES, JUSTIN PIERCE · 2015 to 2024
$3.8M
Development of Beta-Cell-Targeted Regenerative Therapeutics Using A Novel Prodrug StrategyR01DK119955 · NIDDK · STANFORD UNIVERSITY · PI ANNES, JUSTIN PIERCE · 2019 to 2023
$2.1M
Developing A Platform Technology For β-Cell-Targeted Drug DeliveryU01DK136965 · NIDDK · STANFORD UNIVERSITY · PI Justin Pierce Annes · 2023 to 2026
$2.0M
Sciex 6500+ QTrap Mass SpectrometerS10OD030332 · OD · SCRIPPS FLORIDA · PI CAMERON, MICHAEL DARIN · 2021 to 2021
$486k
NIDDK NIH HHS R01 DK101530NIDDK NIH HHS R01 DK119955NIDDK NIH HHS U01 DK136965NIH HHS S10 OD030332
6 · The paper itself

Abstract

Though conceptually attractive, the use of water-soluble prodrug technology to enhance oral bioavailability of highly insoluble small molecule therapeutics has not been widely adopted. In large part, this is due to the rapid enzymatic or chemical hydrolysis of prodrugs within the gastrointestinal tract, resulting in drug precipitation and no overall improvement in oral bioavailability relative to standard formulation strategies. We reasoned that an optimal water-soluble prodrug could be attained if the rate of prodrug hydrolysis were reduced to favor drug absorption rather than drug precipitation. In doing so, the rate of hydrolysis provides a pharmacokinetic control point for drug delivery. Herein, we report the discovery of a water-soluble promoiety (Sol-moiety) technology to optimize the oral bioavailability of highly insoluble small molecule therapeutics, possessing various functional groups, without the need for sophisticated, often toxic, lipid or organic solvent-based formulations. The power of the technology is demonstrated with marked pharmacokinetic improvement of the commercial drugs enzalutamide, vemurafenib, and paclitaxel. This led to a successful efficacy study of a water-soluble orally administered prodrug of paclitaxel in a mouse pancreatic tumor model.

Indexed as

Biological AvailabilityProdrugsSolubilityWaterAdministration, OralAnimalsFemaleHumansHydrolysisMicePaclitaxelPancreatic NeoplasmsPaclitaxelProdrugsWater

Identifiers

PMID39353935
PMCPMC11445516

What OpenQuestion holds

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LicenceCC BY-NC-ND
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.