Historic Compounds

In Kallemeijn W et al 2019 is highlighted the fundamental inability of Tris-DBA palladium to inhibit cellular N-myristoylation while inducing marked cytotoxicity and apoptosis. This evidence invalidates this compound as an NMT inhibitor (PMID: 31006618)

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Tanespimycin, commonly referred as 17-AAG, is an HSP90 inhibitor related to the natural product geldanamycin which has the significant limitation that its potency in cells is highly dependent on the levels of the quinone reductase NQO1 (DT-diaphorase). Human cells with high levels of NQO1 are much more sensitive to tanespimicin/17-AAG than cells having low levels and those lacking activity due to NQO1 polymorphism. This effect is over and above the intrinsic sensitivity of HSP90 inhibition in cells and confounds the interpretation of the involvement of HSP90 in the cellular effects being studied, such as cell proliferation. The mechanism is that NQO1 converts the benzoquinone ansamycin tanespimicin/17-AAG to the hydroquinone form which is a more potent HSP90 inhibitor. The effect was first published by Kelland et al as long ago as 1999 using human cancer cell line panels and an isogenic cell line pair model. The dependence of 17-AAG sensitivity on NQO1 expression has subsequently been confirmed by other groups, most notably using very large human cancer cell line panels. Despite these findings and the discovery of other non-quinone containing HSP90 inhibitory chemotypes, tanespimycin/17-AAG continues to be used as a chemical probe for HSP90. If used at all, alternative chemotypes should also be used alongside tanespimycin/17-AAG, including the recommended resorcinol-class chemical probe luminespib and/or other HSP90 inhibitors such as the resorcinol onalespib and the purine class inhibitor BIIB021. Useful references: (Kelland et al 1999, Workman et al 2012, Guo et al 2006).

Intended target: HHAT; RUSKI-41 inhibited reporter signal under Shh (and HHAT)-independent conditions, and RUSKI-43 is cytotoxic to Shh-Light2 cells, which do not depend on Shh signaling for their survival (EC50=21 uM).

Intended target=PARPs; Flavone is a relatively non-selective PARP inhibitor with insufficient potency, selectivity or validation in cells to be a chemical probe.

Intended target=inhibition of autophagy; Chloroquine is active in cells in the absence of a functioning autophagy pathway (PMID: 26677873).

Intended target=GSKbeta; broad specificity kinase inhibitor.

Intended target=PARPs; CHEMBL3092523 is a relatively non-selective PARP inhibitor with insufficient potency, selectivity or validation in cells to be a chemical probe.

Intended target=BAG1-HSC70 interaction; this class of molecules exhibits multiple off-target activities including CYP1A1-mediated generation of reactive intermediates and DNA adducts (PMID: 20670034).

Intended target=PARPs; IWR-1 is a relatively non-selective PARP inhibitor with insufficient potency, selectivity or validation in cells to be a chemical probe.

Intended target=PARPs; NSC-93392 is a relatively non-selective PARP inhibitor with insufficient potency, selectivity or validation in cells to be a chemical probe.

Intended target=PARPs; 3-Aminobenzoic Acid is a relatively non-selective PARP inhibitor with insufficient potency, selectivity or validation in cells to be a chemical probe.

Intended targets: BAG1, HSC70, CRAF; Thioflavin S is a complex mixture of compounds.

Intended target=PARPs; AG-014376 is a relatively non-selective PARP inhibitor with insufficient potency, selectivity or validation in cells to be a chemical probe.

Intended target=PARPs; CHEMBL301624 is a relatively non-selective PARP inhibitor with insufficient potency, selectivity or validation in cells to be a chemical probe.

Intended target=PARPs; CHEMBL3092539 is a relatively non-selective PARP inhibitor with insufficient potency, selectivity or validation in cells to be a chemical probe.

Intended target=PAK1; FRAX1036 is a lipophilic compound with insufficient potency or selectivity to be a chemical probe.

Intended target=PARPs; Phthalazinone is a relatively non-selective PARP inhibitor with insufficient potency, selectivity or validation in cells to be a chemical probe.

Intended target=PARPs; CHEMBL2179988 is a relatively non-selective PARP inhibitor with insufficient potency, selectivity or validation in cells to be a chemical probe.

Intended target=P53; Pifithrin-beta is unstable and has limited aqueous solubility (PMID: 16170029).

Intended target=cMET; AMG-458 is more potent against RON and inhibits multiple kinases within 10-fold of its IC50 for MET (https://www.ebi.ac.uk/chembl/bioactivity/results/1/cmpd_chemblid/asc/tab...).

Intended target=PARPs; CHEMBL483348 is a relatively non-selective PARP inhibitor with insufficient potency, selectivity or validation in cells to be a chemical probe.

Intended target=MTH1; S-crizotinib's anticancer properties have been attributed to tubulin binding (PMID: 27210421).

Intended target=PARPs; NSC-123414 is a relatively non-selective PARP inhibitor with insufficient potency, selectivity or validation in cells to be a chemical probe.

Intended target=PARPs; CHEMBL3416132 is a relatively non-selective PARP inhibitor with insufficient potency, selectivity or validation in cells to be a chemical probe.

Intended target=Aurora A; MLN8054 binds the GABAA alpha-1 benzodiazepine binding site (PMID: 26101564).

Intended target=PARPs; GJW is a relatively non-selective PARP inhibitor with insufficient potency, selectivity or validation in cells to be a chemical probe.

Intended target=PARPs; CHEMBL2179989 is a relatively non-selective PARP inhibitor with insufficient potency, selectivity or validation in cells to be a chemical probe.

Intended target=Induction of TRAIL pathway (PMID: 23390247); subsequent publications indicate ONC201's antitumor activity is due to TRAIL-dependent and -independent mechanisms, including the induction of a cellular stress response (PMIDs: 26884599, 26884600, 28423492, 28424227, 28700333).

Intended target=PKC kinases; Rottlerin is a broad specificity kinase inhibitor (PMID: 10998351).

Intended target: pan JAK, SYK. Non-selective, more selective pan JAK probes available.

Intended target: HPV E6-E6AP (protein-protein interaction) inhibitor; the compounds are not sufficiently potent nor validated (PMID: 16690141).

Intended target: HPV E6-E6AP (protein-protein interaction) inhibitor; the compounds are not sufficiently potent nor validated (PMID: 16690141).

Intended target: HPV E6-E6AP (protein-protein interaction) inhibitor; the compounds are not sufficiently validated (PMID: 24854633).

Intended target: HPV E6-E6AP (protein-protein interaction) inhibitor; the compounds are not sufficiently validated (PMID: 24854633).

Intended target: HPV E6-E6AP (protein-protein interaction) inhibitor; the compounds are not sufficiently validated (PMID: 24854633).

Intended target: HPV E6-E6AP (protein-protein interaction) inhibitor; the compounds are not sufficiently potent nor validated (PMID: 16690141).

Intended target: HPV E6-E6AP (protein-protein interaction) inhibitor; the compounds are not sufficiently validated (PMID: 24854633).

Intended target: HPV E6-E6AP (protein-protein interaction) inhibitor; the compounds are not sufficiently potent nor validated (PMID: 16690141).

Intended target: MDM2; Compounds with superior potency are available (PMID: 25396320).

Intended target: MDM2; Compounds with superior potency are available (PMID: 25396320).

Intended target: MDM2, Nutlins were the first small molecule antagonists of MDM2 reported (PMID: 14704432) but they have been superceded by more potent molecules (PMID: 25396320).

Intended target: MDM2; Compounds with superior potency are available (PMID: 25396320).

Class I HDAC inhibitor. Bradner et al., Chemical Phylogenetics of Histone Deacetylases. Nat. Chem. Biol. 6, 238-43 (2010).

Inhibitor of HDAC1, HDAC2 and HDAC3. Bradner et al., Chemical Phylogenetics of Histone Deacetylases. Nat. Chem. Biol. 6, 238-43 (2010).

Potent class I HDAC inhibitor. Bradner et al., Chemical Phylogenetics of Histone Deacetylases. Nat. Chem. Biol. 6, 238-43 (2010).

Potent class I HDAC inhibitor. Bradner et al., Chemical Phylogenetics of Histone Deacetylases. Nat. Chem. Biol. 6, 238-43 (2010).

Intended target: EGFR, ERBB2; In proteomic experiments, gefitinib interacts with several protein tyrosine kinases BRK, YES, CSK, and EPHB4, and the serine/threonine kinases RICK (RIPK2, RIP2, and CARDIAK), GAK, CaMKII, Aurora A, JNK2 and p38. Brehmer et al., Cellular targets of gefitinib. Cancer Res 65, 379-82 (2005). In AML and EGFR-expressing cells, gefitinib binds to and modulates the activity of histamine receptors (H2 and H4); Yadav et al., Epidermal growth factor receptor inhibitor cancer drug gefitinib modulates cell growth and differentiation of acute myeloid leukemia cells via histamine receptors. Biochim Biophys Acta. 1860, 2178-90 (2016).

Intended target=EP300, CREBBP (p300/CBP); this compound is weakly potent (IC50 ~1 mM) against these targets in biochemical assays. It is not a chemical probe. Shirakawa et al., Salicylate, diflunisal and their metabolites inhibit CBP/p300 and exhibit anticancer activity. Elife. 5, pii: e11156 (2016).

Hydroxamate - non-selective HDAC inhibitor; Shortt, J., et al., A chemical probe toolbox for dissecting the cancer epigenome. Nat Rev Cancer. 17, 160-183 (2017).

Hydroxamate - non-selective HDAC inhibitor; Shortt, J., et al., A chemical probe toolbox for dissecting the cancer epigenome. Nat Rev Cancer. 17, 160-183 (2017).

Intended target=HATs; pleiotrophic effects on cell signaling; Shortt, J., et al., A chemical probe toolbox for dissecting the cancer epigenome. Nat Rev Cancer. 17, 160-183 (2017).

Hydroxamate - non-selective HDAC inhibitor; Shortt, J., et al., A chemical probe toolbox for dissecting the cancer epigenome. Nat Rev Cancer. 17, 160-183 (2017).

Hydroxamate - non-selective HDAC inhibitor; Shortt, J., et al., A chemical probe toolbox for dissecting the cancer epigenome. Nat Rev Cancer. 17, 160-183 (2017).

Anti-inflammatory compound with cellular activity in the mM range against p300/CBP; Shortt, J., et al., A chemical probe toolbox for dissecting the cancer epigenome. Nat Rev Cancer. 17, 160-183 (2017).

Hydroxamate - non-selective HDAC inhibitor; Shortt, J., et al., A chemical probe toolbox for dissecting the cancer epigenome. Nat Rev Cancer. 17, 160-183 (2017).

Hydroxamate - non-selective HDAC inhibitor; Shortt, J., et al., A chemical probe toolbox for dissecting the cancer epigenome. Nat Rev Cancer. 17, 160-183 (2017).

Hydroxamate - non-selective HDAC inhibitor; Shortt, J., et al., A chemical probe toolbox for dissecting the cancer epigenome. Nat Rev Cancer. 17, 160-183 (2017).

Intended target: BET bromodomains; weaker than other available inhibitors; Shortt, J., et al., A chemical probe toolbox for dissecting the cancer epigenome. Nat Rev Cancer. 17, 160-183 (2017).

Non-selective MAOI, also inhibits LSD1; Shortt, J., et al., A chemical probe toolbox for dissecting the cancer epigenome. Nat Rev Cancer. 17, 160-183 (2017).

Intended target: Sirtuins; also inhibits multiple kinases; Shortt, J., et al., A chemical probe toolbox for dissecting the cancer epigenome. Nat Rev Cancer. 17, 160-183 (2017).

Hydroxamate - non-selective HDAC inhibitor; Shortt, J., et al., A chemical probe toolbox for dissecting the cancer epigenome. Nat Rev Cancer. 17, 160-183 (2017).

Hydroxamate - non-selective HDAC inhibitor; Shortt, J., et al., A chemical probe toolbox for dissecting the cancer epigenome. Nat Rev Cancer. 17, 160-183 (2017).

Pandacostat was designed to be a pan-HDAC inhibitor (Bradner et al., Chemical Phylogenetics of histone deacetylases. Nat Chem Biol 6, 238-243 (2010).

Intended target=protein methyltransferase; this compound results in SAH accumulation, which feeds back to inhibit SAM-dependent methylation but this mechanism is not specific enough to study specific methyltransferases. Shortt, J., et al., A chemical probe toolbox for dissecting the cancer epigenome. Nat Rev Cancer. 17, 160-183 (2017).

Short chain fatty acid, weak class I HDAC inhibitor; Shortt, J., et al., A chemical probe toolbox for dissecting the cancer epigenome. Nat Rev Cancer. 17, 160-183 (2017).

Hydroxamate - non-selective HDAC inhibitor; Shortt, J., et al., A chemical probe toolbox for dissecting the cancer epigenome. Nat Rev Cancer. 17, 160-183 (2017).

Intended target: BCL2; Apogossypol induces proaptotic NOXA; Soderquist & Eastman. BCL2 inhibitors as anticancer drugs: a plethora of misleading BH3 mimetics. Mol Cancer Ther. 15, 2011-7 (2016).

Intended target: BCL2; TW37 induces proaptotic NOXA; Soderquist & Eastman. BCL2 inhibitors as anticancer drugs: a plethora of misleading BH3 mimetics. Mol Cancer Ther. 15, 2011-7 (2016).

Intended target=PARPs; Iniparib non-specifically modified Cys-containing proteins; Liu et al., Iniparib nonselectively modifies cysteine-containing proteins in tumor cells and is not a bona fide PARP inhibitor. Clin Cancer Res. 18, 510-23 (2012).

Intended target: BCL2; MIM1 induces proaptotic NOXA; Soderquist & Eastman. BCL2 inhibitors as anticancer drugs: a plethora of misleading BH3 mimetics. Mol Cancer Ther. 15, 2011-7 (2016).

Intended target: BCL2; Obatoclax yields cellular outcomes that are not consistent with specificity for BCL2, including MEK-ERK inhibition; Soderquist & Eastman. BCL2 inhibitors as anticancer drugs: a plethora of misleading BH3 mimetics. Mol Cancer Ther. 15, 2011-7 (2016).

Intended target: BCL2; Antimycin A induces proaptotic NOXA; Soderquist & Eastman. BCL2 inhibitors as anticancer drugs: a plethora of misleading BH3 mimetics. Mol Cancer Ther. 15, 2011-7 (2016).

Intended target: BCLXL; BH3I-1 induces apoptosis in Bax/Bak-deficient cells; Van Delft et al. The BH3 mimetic ABT-737 targets selective Bcl-2 proteins and efficiently induces apoptosis via Bak/Bax if Mcl-1 is neutralized. Cancer Cell. 10, 389-99 (2006).

Intended target: BCL2; Gossypol has multiple reported mechanims of action, including agonizing phospholipase A2 and induction of NOXA; Soderquist & Eastman. BCL2 inhibitors as anticancer drugs: a plethora of misleading BH3 mimetics. Mol Cancer Ther. 15, 2011-7 (2016).

Intended target: BCL2; BXI-72 induces proaptotic NOXA; Soderquist & Eastman. BCL2 inhibitors as anticancer drugs: a plethora of misleading BH3 mimetics. Mol Cancer Ther. 15, 2011-7 (2016).

Intended target=MCL1; Maritoclax is a natural product that was reported as a BH3 mimetic specific for MCL1 (https://www.ncbi.nlm.nih.gov/pubmed/22311987). Subsequent studies have challenged maritoclax’s selectivity for MCL1 over other BCL2 proteins (https://www.ncbi.nlm.nih.gov/pubmed/24157874, https://www.ncbi.nlm.nih.gov/pubmed26059440) and reported additional cellular targets (https://www.ncbi.nlm.nih.gov/pubmed/28154844).

Non selective compound: Aloisine is a broad specificity kinase inhibitor.

Broad specificity kinase inhibitor; Menichincheri et al., Discovery of Entrectinib: A New 3-Aminoindazole As a Potent Anaplastic Lymphoma Kinase (ALK), c-ros Oncogene 1 Kinase (ROS1), and Pan-Tropomyosin Receptor Kinases (Pan-TRKs) inhibitor. J Med Chem 59, 3392-408 (2016).

Broad specificity tyrosine kinase inhibitor, with known activity against tyrosine kinases WEE1, MYT1, EERB1, FGFR1, PDGFRbeta, SRC, LCK.

Non-selective PARP inhibitor. Thorsell et al., Structural Basis for Potency and Promiscuity in Poly(ADP-ribose) Polymerase (PARP) and Tankyrase Inhibitors. J Med Chem. (2016).

Foretinib is a multitargetd tyrosine kinase inhibitor: Intended target=MET; Actual targets include MET, PDGFRs, TIE2, FLT3, VEGFRs, KIT

Broad specificity BCL2 protein inhibitor: Intended target=BCL2; This is a high quality compound that inhibits multiple BCL2 proteins. Tse et al., ABT-263: a potent and orally bioavailable Bcl-2 family inhibitor. Cancer Res 68, 3421-8 (2008).

Broad specificiy kinase inhibitor: Sorafenib bound ~10% of kinases in a panel of 317 within 10-fold of the primary target. Karaman et al., 2008. Nat. Biotech. 26, 127-132.

Broad specificity kinase inhibitor: Intended target=Aurora kinases

Intended target CSF1R; Available data reveal limited profiling against kinases, and insufficient evidence to establish that this compound is acting on the intended target in cells; Ohno et al. A c-fms tyrosine kinase inhibitor, Ki20227, suppresses osteoclast differentiation and osteolytic bone destruction in a bone metastasis model. Mol Cancer Ther. 5, 2634-43 (2006).

Intended target=RSK2; SL0101 is a natural product ATP-competitive kinase inhibitor; Limited validation data are available regarding the activity of this compound against kinases. Smith et al. Identification of the first specific inhibitor of p90 ribosomal S6 kinase (RSK) reveals an unexpected role for RSK in cancer cell proliferation. Cancer Res. 65, 1027-34 (2005).

IPA-3 is an uncompetitive PAK1 inhibitor. While this compound is a selective, covalent binder of PAK1 (targeting its autoregulatory domain), its redox activity makes it a poor tool; cells exposed to this compound may rapidly change their redox potential due to the continuous reduction of the reactive sulfhydryl moiety. As a consequence, cells can be very sensitive to this compound independent of any specific effects on PAK1. For further reference, see Rudolph et al., Inhibitors of p21-Activated Kinases (PAKs) J. Med Chem. 2015 58, 111-129. As there are other specific ATP-competitive PAK inhibitors available, there should be no reason to use this tool any longer.

Cys reactive compound: Intended targets=E1A binding protein p300, CREB binding protein; Reacts with Cys-rich proteins including tubulins and inhibits tubulin polymerization; Shrimp et al., Characterizing the Covalent Targets of a Small Molecule Inhibitor of the Lysine Acetyltransferase P300. ACS Med Chem Lett. 7, 151-5 (2015).

Non selective compound: Intended target=PRKCB; Number of targets=395; Wang et al., Evidence-based and quantitative prioritization of tool compounds in phenotypic drug discovery Cell Chem. Biol. 23, 862-874 (2016).

Non selective compound: Intended target=AURKA; Number of targets=123; Wang et al., Evidence-based and quantitative prioritization of tool compounds in phenotypic drug discovery Cell Chem. Biol. 23, 862-874 (2016).

Non selective compound: Intended target=DRD2; Number of targets=174; Wang et al., Evidence-based and quantitative prioritization of tool compounds in phenotypic drug discovery Cell Chem. Biol. 23, 862-874 (2016).

Non selective compound: Intended target=MAPK8; Number of targets=146; Wang et al., Evidence-based and quantitative prioritization of tool compounds in phenotypic drug discovery Cell Chem. Biol. 23, 862-874 (2016).

Non selective compound: Intended target=CDC7; Number of targets=118; Wang et al., Evidence-based and quantitative prioritization of tool compounds in phenotypic drug discovery Cell Chem. Biol. 23, 862-874 (2016).

Non selective compound: Intended target=CSNK2A1; Number of targets=215; Wang et al., Evidence-based and quantitative prioritization of tool compounds in phenotypic drug discovery Cell Chem. Biol. 23, 862-874 (2016).

Non selective compound: Intended target=KCNH2; Number of targets=103; Wang et al., Evidence-based and quantitative prioritization of tool compounds in phenotypic drug discovery Cell Chem. Biol. 23, 862-874 (2016).

Non selective compound: Intended target=PLK1; Number of targets=114; Wang et al., Evidence-based and quantitative prioritization of tool compounds in phenotypic drug discovery Cell Chem. Biol. 23, 862-874 (2016).

Non selective compound: Intended target=CDC7; Number of targets=105; Wang et al., Evidence-based and quantitative prioritization of tool compounds in phenotypic drug discovery Cell Chem. Biol. 23, 862-874 (2016).

Non selective compound: Intended target=mapk8; Number of targets=100; Wang et al., Evidence-based and quantitative prioritization of tool compounds in phenotypic drug discovery Cell Chem. Biol. 23, 862-874 (2016).

Non selective compound: Intended target=AKR1B1; Number of targets=312; Wang et al., Evidence-based and quantitative prioritization of tool compounds in phenotypic drug discovery Cell Chem. Biol. 23, 862-874 (2016).

Non selective compound: Intended target=CCND1; Number of targets=176; Wang et al., Evidence-based and quantitative prioritization of tool compounds in phenotypic drug discovery Cell Chem. Biol. 23, 862-874 (2016).

Non selective compound: Intended target=SLC29A2; Number of targets=113; Wang et al., Evidence-based and quantitative prioritization of tool compounds in phenotypic drug discovery Cell Chem. Biol. 23, 862-874 (2016).

Non selective compound: Intended target=ABL1; Number of targets=239; Wang et al., Evidence-based and quantitative prioritization of tool compounds in phenotypic drug discovery Cell Chem. Biol. 23, 862-874 (2016).

Non selective compound: Intended target=ALK; Number of targets=299; Wang et al., Evidence-based and quantitative prioritization of tool compounds in phenotypic drug discovery Cell Chem. Biol. 23, 862-874 (2016).

Non selective compound: Intended target=KDR; Number of targets=141; Wang et al., Evidence-based and quantitative prioritization of tool compounds in phenotypic drug discovery Cell Chem. Biol. 23, 862-874 (2016).

Non selective compound: Intended target=PTK2; Number of targets=122; Wang et al., Evidence-based and quantitative prioritization of tool compounds in phenotypic drug discovery Cell Chem. Biol. 23, 862-874 (2016).

Non selective compound: Intended target=KCNH2; Number of targets=149; Wang et al., Evidence-based and quantitative prioritization of tool compounds in phenotypic drug discovery Cell Chem. Biol. 23, 862-874 (2016).

Non selective compound: Intended target=CYP19A1; Number of targets=193; Wang et al., Evidence-based and quantitative prioritization of tool compounds in phenotypic drug discovery Cell Chem. Biol. 23, 862-874 (2016).

Non selective compound: Dinaciclib is a nonselective CDK inhibitor.

Non selective compound: Intended target=JAK2; Number of targets=274; Wang et al., Evidence-based and quantitative prioritization of tool compounds in phenotypic drug discovery Cell Chem. Biol. 23, 862-874 (2016).

Non selective compound: Intended target=MTOR; Number of targets=203; Wang et al., Evidence-based and quantitative prioritization of tool compounds in phenotypic drug discovery Cell Chem. Biol. 23, 862-874 (2016).

Non selective compound: Intended target=CDK1; Number of targets=184; Wang et al., Evidence-based and quantitative prioritization of tool compounds in phenotypic drug discovery Cell Chem. Biol. 23, 862-874 (2016).

Non selective compound: Intended target=FLT3; Number of targets=203; Wang et al., Evidence-based and quantitative prioritization of tool compounds in phenotypic drug discovery Cell Chem. Biol. 23, 862-874 (2016).

Non selective compound: Intended target=ABL1; Number of targets=114; Wang et al., Evidence-based and quantitative prioritization of tool compounds in phenotypic drug discovery Cell Chem. Biol. 23, 862-874 (2016).

Non selective compound: Intended target=FLT3; Tandutinib inhibits type III receptor tyrosine kinases.

Non selective compound: Intended target=CDK5; Number of targets=108; Wang et al., Evidence-based and quantitative prioritization of tool compounds in phenotypic drug discovery Cell Chem. Biol. 23, 862-874 (2016).

Non selective compound: Intended target=NFKB1; Number of targets=123; Wang et al., Evidence-based and quantitative prioritization of tool compounds in phenotypic drug discovery Cell Chem. Biol. 23, 862-874 (2016).

Non selective compound: Intended target=IFNG; Number of targets=125; Wang et al., Evidence-based and quantitative prioritization of tool compounds in phenotypic drug discovery Cell Chem. Biol. 23, 862-874 (2016).

Non selective compound: Intended target=CYP19A1; Number of targets=113; Wang et al., Evidence-based and quantitative prioritization of tool compounds in phenotypic drug discovery Cell Chem. Biol. 23, 862-874 (2016).

Non selective compound: Intended target=ABCB1; Number of targets=143; Wang et al., Evidence-based and quantitative prioritization of tool compounds in phenotypic drug discovery Cell Chem. Biol. 23, 862-874 (2016).

Non selective compound: Intended target=ABL1; Number of targets=273; Wang et al., Evidence-based and quantitative prioritization of tool compounds in phenotypic drug discovery Cell Chem. Biol. 23, 862-874 (2016).

Non selective compound: Intended target=KDR; Number of targets=102; Wang et al., Evidence-based and quantitative prioritization of tool compounds in phenotypic drug discovery Cell Chem. Biol. 23, 862-874 (2016).

Non selective compound: Intended target=XDH; Number of targets=159; Wang et al., Evidence-based and quantitative prioritization of tool compounds in phenotypic drug discovery Cell Chem. Biol. 23, 862-874 (2016).

Due to its poor selectivity profile GF109203X is classified as Historical Compound.

Epiblastin A inhibit casein kinase 1 (CK1) isoforms with half maximal inhibitory concentration (IC50) values of 33.5 μM, 6.9 μM, and 30.4 μM for CK1α, CK1δ, and CK1ɛ isoforms, respectively. Selectivity analysis revealed that it further inhibits brain-selective kinase 1 (BRSK1; IC50 = 24.2 ± 5.8 μM), eukaryotic elongation factor 2 kinase (EEF2K; IC50 = 27.4 ± 5.6 μM), epidermal growth factor receptor kinase (EGFR; IC50 = 8.3 ± 1.5 μM), Map kinase-interacting Ser/Thr kinase 2 (MKNK2; IC50 = 45.0 ± 10.3 μM), and receptor-interacting Ser/Thr kinase 2 (RIPK2; IC50 = 38.0 ± 11.3 μM). Given the low potency and poor selectivity we consider Epiblastin A an Historical Compound and we do not suggest its use to interrogate target activity in cells.

Non-selective PRMT inhibitor; Shortt, J., et al., A chemical probe toolbox for dissecting the cancer epigenome. Nat Rev Cancer. 17, 160-183 (2017).

Non selective compound; Intended target=PI3K. There are far better chemical probes for PI3K available.