ArticleCommunications medicine2026
Discovery of potent kinase inhibitors with improved pharmacokinetics and safety potentials through structural optimization of dasatinib.
Article in Communications medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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.
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.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDasatinib exhibits broad therapeutic potentials for several diseases; however, its clinical application is limited by safety concerns and unfavorable pharmacokinetics.
methodsStructural optimization of dasatinib yielded PDD-87. Preclinical studies evaluated kinase inhibition, antiproliferative activity in leukemia and lymphoma cell lines, antitumor effects in a xenograft model, pharmacokinetics and metabolism in vitro and in rodents, and exploratory safety in mice.
resultsHere we show that PDD-87 strongly inhibits ABL and BTK along with their key mutants, and SRC family kinases (IC₅₀ <1 nM), displaying potent antiproliferative effects against several leukemia and lymphoma cell lines. In a K-562G mouse xenograft model, PDD-87 significantly reduces tumor growth in a dose-dependent manner. Compared to dasatinib, PDD-87 exhibits lower clearance (405 vs 989 mL/hr/kg), reduced volume of distribution (0.9 vs 2.4 mL/hr/kg), higher plasma exposure (2521 vs 190 hr*pmol/mL for oral dose), and improved oral bioavailability (18.9 vs 3.9%) in rats. PDD-87 demonstrates lower metabolic clearance than dasatinib in human, mouse, rat, and dog liver microsomes. Metabolically, PDD-87 undergoes hydroxylation on the 2-chloro-6-methylphenyl ring, followed by sulfation, and glucuronidation. Significantly, PDD-87 shows markedly lower lung accumulation than dasatinib, suggesting a reduced risk of pulmonary toxicity. The lung/plasma ratios of Cmax and AUClast for PDD-87 are 2 and 4, respectively, compared to 12 and 22 for dasatinib. Additionally, PDD-87 is well-tolerated in mice at doses up to 200 mg/day for two weeks, with no overt toxicity.
conclusionsPDD-87 is a highly potent, selective kinase inhibitor with improved pharmacokinetics and safety potentials, holding promise for broader clinical applications.
Identifiers
What OpenQuestion holds
Registered trials
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.