Evidence map›Paper›PMID 42305204›Full record

ArticleACS medicinal chemistry letters2026

Synthesis and Biochemical Characterization of Investigational Pyrazolopyrimidine-Based Allosteric KRAS Modulators.

Cynthia V Pagba, Kasuni Dilsha, Rakshya Ojha, Jacob Jakubec, Xiaowen Liang, Abraham C Sianoya, Paul Mark B Medina, Scott Gilbertson, Alemayehu A Gorfe

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in ACS medicinal chemistry letters, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Cynthia V PagbaDepartment of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston, 6431 Fannin Street, Houston, Texas 77030, United States.ORCID https://orcid.org/0000-0002-3642-4361
Kasuni DilshaDepartment of Chemistry, University of Houston, 3585 Cullen Blvd., Houston, Texas 77204, United States.
Rakshya OjhaDepartment of Chemistry, University of Houston, 3585 Cullen Blvd., Houston, Texas 77204, United States.
Jacob JakubecDepartment of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston, 6431 Fannin Street, Houston, Texas 77030, United States.
Xiaowen LiangDepartment of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston, 6431 Fannin Street, Houston, Texas 77030, United States.ORCID https://orcid.org/0000-0002-6174-2951
Abraham C SianoyaDepartment of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston, 6431 Fannin Street, Houston, Texas 77030, United States.
Paul Mark B MedinaBiological Models Laboratory, Department of Biochemistry and Molecular Biology, College of Medicine, University of the Philippines Manila, Manila 2801, Philippines.
Scott GilbertsonDepartment of Chemistry, University of Houston, 3585 Cullen Blvd., Houston, Texas 77204, United States.ORCID https://orcid.org/0000-0003-3665-5693
Alemayehu A GorfeDepartment of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston, 6431 Fannin Street, Houston, Texas 77030, United States.ORCID https://orcid.org/0000-0002-9328-4692

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

We describe the synthesis and biochemical characterization of a series of compounds derived from a previously reported pyrazolopyrimidine-based KRAS inhibitor [ACS Omega2019, 4 (2), 2921-2930]. Dozens of derivatives were made primarily by modifying the substituents of the pyrazolo-pyrimidine core with the goal of increasing binding affinity to KRAS and improving inhibitory activities against wild-type and oncogenic mutants of KRAS using biophysical measurements and cell proliferation assays. We show that while many of the new compounds exhibited a dramatic increase in binding affinity to KRAS, in many cases, that did not translate into improved potency in inhibiting cell growth. Considering the high binding affinities (up to single-digit nanomolar) and low micromolar inhibitory activities across multiple KRAS mutant cancer cells, we propose that these new derivatives will serve as useful investigational agents for KRAS studies or as starting points for further derivatization and structure-activity relationship studies.

Indexed as

cell growth assayschemical synthesisinhibition of KRAS-Raf interactionKRAS modulatorspyrazolopyrimidine allosteric inhibitors

Identifiers

PMID42305204
PMCPMC13266632

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.