Journal of Medicinal Chemistry
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Funding Sources
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The authors would like to thank the National Institutes of
Health for their generous financial support through grants R01
CA197329 (to N.S.G., subcontracted to S.D.P.), R01
NS089815 and R03 CA250020 (to J.A.M.), as well as R35
CA197588, R01 GM041890, and U54 CA210184 (to L.C.C.).
This work was further supported by the Breast Cancer Research
Foundation (to L.C.C.) and the NIH intramural research pro-
gram (NCATS).
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ABBREVIATIONS
ACVR2A, activin A receptor type 2A; ACVR2B, activin A
receptor type 2B; ATCC, American type culture collection;
BMPR1B, bone morphogenetic protein receptor type 1B; calc,
calculated; CETSA, cellular thermal shift assay; CHAPS, 3-((3-
cholamidopropyl) dimethylammonio)-1-propanesulfonate; CV,
coefficient of variation; DMEM, Dulbecco’s modified eagle
medium; DPPS, 1,2-dipalmitoyl-sn-glycero-3-phosphoserine,
sodium salt; EGTA, ethylene glycol-bis(β-aminoethyl ether)-
N,N,N’,N’-tetraacetic acid; FBS, fetal bovine serum; Hepes, 4-
(2-hydroxyethyl)-1-piperazineethanesulfonic acid; MEK3, mi-
togen-activated protein kinase kinase 3; NCATS, national cen-
ter for advancing translational studies; NIH, national institutes
of health; PAINS, pan-assay interference compounds; PAMPA,
parallel artificial membrane permeability assay; Pd2(dba)3,
tris(dibenzylideneacetone)dipalladium(0); PI-4,5-P2, phospha-
tidylinositol-4,5-bisphosphate; PI5P, phosphatidylinositol-5-
phosphate; PI5P4K, phosphatidylinositol 5-phosphate 4-ki-
nases; PI4P5K, phosphatidylinositol-4-phosphate 5-kinase; S35,
selectivity score for hits with percent control < 35; RLU, rela-
tive light units; SD, standard deviation; TGFβ, transforming
growth factor beta; TGFBR2, transforming growth factor beta
receptor 2; UPLC, ultra-high pressure liquid chromatography;
X-Phos,
2-dicyclohexylphosphino-2’,4’,6’-triisopropylbi-
phenyl.
PDB code for PI5P4Kα with bound CVM-05-002 is 6UX9.
Authors will release the atomic coordinates and experimental
data upon article publication.
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