Genomic analyses of cancer have identified recurrent point mutations in the RNA splicing factor-encoding genes SF3B1, U2AF1, and SRSF2 that confer an alteration of function. Cancer cells bearing these mutations are preferentially dependent on wild-type (WT) spliceosome function, but clinically relevant means to therapeutically target the spliceosome do not currently exist. Here we describe an orally available modulator of the SF3b complex, H3B-8800, which potently and preferentially kills spliceosome-mutant epithelial and hematologic tumor cells. These killing effects of H3B-8800 are due to its direct interaction with the SF3b complex, as evidenced by loss of H3B-8800 activity in drug-resistant cells bearing mutations in genes encoding SF3b components. Although H3B-8800 modulates WT and mutant spliceosome activity, the preferential killing of spliceosome-mutant cells is due to retention of short, GC-rich introns, which are enriched for genes encoding spliceosome components. These data demonstrate the therapeutic potential of splicing modulation in spliceosome-mutant cancers.
Pharmacology, Toxicology and Pharmaceutical Science
13
3%
Other
24
6%
Unknown
139
33%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 228. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 10 September 2025.
All research outputs
#211,620
of 34,568,501 outputs
Outputs from Nature Medicine
#996
of 11,599 outputs
Outputs of similar age
#3,964
of 373,742 outputs
Outputs of similar age from Nature Medicine
#11
of 65 outputs
Altmetric has tracked 34,568,501 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 99th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 11,599 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 110.6. This one has done particularly well, scoring higher than 91% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 373,742 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 98% of its contemporaries.
We're also able to compare this research output to 65 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 83% of its contemporaries.
