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Fig. 1 · Structure
Cat. No.
A11612
CAS No.
1037184-44-3
Formula
C17H13Cl2NO4
Mol. Weight
366.2

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YK 4-279

RHA inhibitor

YK 4-279 is an inhibitor of RNA Helicase A (RHA) binding to the oncogenic transciption factor EWS-FLI1.

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Publications for YK 4-279

1 publication citing this product

  1. Christopher M Schafer, .et al. , Proc Natl Acad Sci U S A, 2020, Oct 20;117(42):26494-26502 PMID: 33020273
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Biological Activity

Bioactivity / Mechanism

YK-4-279 was reported to bind recombinant EWS-FLI1 with a KD of 9.48 μM and to reduce EWS-FLI1 interaction with an RNA helicase A fragment in cell-free assays. These findings support its use as a protein-interaction probe; they do not establish exclusive cellular target selectivity. [1]

Literature-reported observations and conditions; not Adooq-tested protocols or general treatment recommendations.

Target & Activity

Target Activity Value
RNA helicase A

Cellular Effect

Cell Line Activity Value Description Reference
COS-7 IC50 0.35 μM Inhibition of transcriptional activity of full-length EWS-FLI1 (unknown origin) expressed in COS7 cells by NR0B1-luciferase reporter gene assay [PMID: 25432018]
PANC-1 GI50 > 10 μM Growth inhibition of human PANC1 cells after 3 days by WST1 assay [PMID: 25432018]
TC-32 GI50 0.94 μM Growth inhibition of human TC32 cells harboring EWS-FLI1 fusion protein after 3 days by WST1 assay [PMID: 25432018]

In Vitro Studies

In the original seven-day TC32 monolayer assay, YK-4-279 had a reported IC50 of 900 nM, compared with 20 μM for precursor NSC635437. This value is specific to that assay and exposure duration. [1]

In a separate 72-hour WST panel, racemic YK-4-279 had IC50 values of 0.33–1.83 μM across seven Ewing sarcoma cell lines; resolved (S)-YK-4-279 was generally more potent. Sensitivity extended to non-Ewing models: racemate IC50 values were 0.82 (0.02) μM in MDA-MB-231 and 1.514 (0.6503) μM in PANC1 (parentheses indicate SEM). Purified-enantiomer results should not be treated as specifications for stereochemically unspecified catalog material. [2]

EWS-FLI1 binding and RHA interaction disruption

Biochemical assay · Recombinant EWS-FLI1; GST-RHA(647–1075) interaction assay; E9R peptide displacement [1]

YK-4-279 bound immobilized EWS-FLI1 and reduced its interaction with the RHA fragment in a cell-free assay. E9R displacement provided an additional interaction readout. These assays do not establish exclusive cellular target selectivity.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
Binding of YK-4-279 to immobilized recombinant EWS-FLI1KD 9.48 μM[1]
RHA fragment coprecipitated with EWS-FLI1Qualitative interaction inhibition Reduced GST-RHA(647–1075) binding at 10 μM YK-4-279[1]
Displacement of FITC-E9R from EWS-FLI1Qualitative displacement Complete displacement reported at 30 μM YK-4-279[1]

Literature-Reported Treatment Conditions

Treatment concentration
10 μM in Fig. 3b; titrated for SPR and fluorescence polarization; 30 μM displacement endpoint
Method
Cell-free protein binding and interaction assays
Co-treatment
E9R peptide used as a mechanistic displacement reagent, not an anticancer drug combination
Reported limits
Incubation duration and small-molecule vehicle for these selected binding assays are not specified in the acquired main-text locations; SI was not retrieved.
Methods and source locations

Compound reported in the paper: YK-4-279; Compound label in the paper: YK-4-279 (para-methoxy derivative)

Compound-level activity; KD is a binding endpoint, not a cell-treatment dose or IC50.

Fig. 3a–e; Results: Methoxy-derivative is a more potent inhibitor; Methods: protein immunoprecipitation, SPR screening, fluorescence polarization

Binding of YK-4-279 to immobilized recombinant EWS-FLI1: Surface plasmon resonance, steady-state binding on a CM5 Biacore chip — Fig. 3c and Results: Methoxy-derivative is a more potent inhibitor

RHA fragment coprecipitated with EWS-FLI1: FLI1 antibody pull-down with EWS-FLI1 and GST-RHA fragment; input/partner controls shown — Fig. 3b right panel and caption

Displacement of FITC-E9R from EWS-FLI1: Fluorescence polarization; FITC-E9R 3.2 μM; increasing YK-4-279 — Fig. 3e; Results: Methoxy-derivative; Methods: Fluorescence polarization assay

Seven-day TC32 cell-growth response

Cell-based study · TC32 Ewing sarcoma cells in monolayer culture [1]

YK-4-279 was more potent than its lead precursor NSC635437 in the seven-day TC32 assay. This experiment alone does not establish selectivity across tumor types.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
TC32 cell number/viability relative to control after seven daysIC50 900 nM[1]
TC32 response to precursor NSC635437IC50 20 μM[1]

Literature-Reported Treatment Conditions

Treatment concentration
Dose range shown in Fig. 5a; IC50 is an assay result
Exposure duration
7 days
Method
Compound addition to monolayer TC32 culture; RPMI with 10% FBS
Co-treatment
Single compounds compared separately (YK-4-279 versus NSC635437)
Reported limits
The acquired Fig. 5a caption does not distinguish MTT from WST for this panel; vehicle composition, final solvent percentage and replicate definition for this specific curve are not stated there. No conditions were borrowed from the three-day assays.
Methods and source locations

Compound reported in the paper: YK-4-279

Seven-day TC32 assay only; do not generalize this potency to other exposure times or catalog lots.

Fig. 5a and caption; Results: YK-4-279 specifically inhibits ESFT cell growth; Methods: Cell cultures

TC32 cell number/viability relative to control after seven days: MTT or WST reduction, as specified jointly in Fig. 5a caption — Fig. 5a and caption; Results: YK-4-279 specifically inhibits ESFT cell growth

TC32 response to precursor NSC635437: Monolayer cell-growth comparison with YK-4-279 — Fig. 5a; Results: YK-4-279 specifically inhibits ESFT cell growth

Stereochemistry and cell-model dependence of viability inhibition

Cell-based study · Seven ESFT lines (TC32, TC71, RDES, SKES, MMH-ES-1, STA-ET 7.2, A4573) and five non-ESFT carcinoma lines (PC3, MCF7, MDA-MB-231, PANC1, ASPC1) [2]

The resolved (S) enantiomer generally inhibited ESFT viability more strongly than the racemate; (R) was substantially less potent. Non-ESFT lines included sensitive MDA-MB-231 and PANC1 cultures, so sensitivity cannot be treated as restricted to EWS-FLI1-positive cells. No significant racemate-versus-(S) difference was reported in the non-ESFT panel.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
WST viability IC50 across seven ESFT lines after 72 hIC50 range Racemate: 0.33–1.83 μM; (S): 0.16–0.87 μM; (R): 11.69–25.98 μM[2]
72-hour WST viability, TC32IC50 (SEM) Racemate: 0.94 (0.14); (S): 0.28 (0.06); (R): 16.30 (4.83) μM (parentheses: SEM)[2]
72-hour WST viability, TC71IC50 (SEM) Racemate: 1.83 (0.41); (S): 0.16 (0.02); (R): 20.86 (7.8) μM (parentheses: SEM)[2]
72-hour WST viability, RDESIC50 (SEM) Racemate: 1.03 (0.19); (S): 0.87 (0.64); (R): 12.71 (0.11) μM (parentheses: SEM)[2]
72-hour WST viability, SKESIC50 (SEM) Racemate: 0.33 (0.03); (S): 0.18 (0.01); (R): 21.01 (3.91) μM (parentheses: SEM)[2]
72-hour WST viability, MMH-ES-1IC50 (SEM) Racemate: 0.94 (0.13); (S): 0.34 (0.08); (R): 25.98 (4.03) μM (parentheses: SEM)[2]
72-hour WST viability, STA-ET 7.2IC50 (SEM) Racemate: 0.60 (0.04); (S): 0.31 (0.01); (R): 21.25 (3.49) μM (parentheses: SEM)[2]
72-hour WST viability, A4573IC50 (SEM) Racemate: 1.46 (0.31); (S): 0.23 (0.08); (R): 11.69 (6.56) μM (parentheses: SEM)[2]
72-hour WST viability, PC3IC50 (SEM) Racemate: 4.95 (3.62); (S): 3.79 (3.16); (R): >30 (0) μM (parentheses: SEM)[2]
72-hour WST viability, MCF7IC50 (SEM) Racemate: 22.82 (7.19); (S): 19.47 (10.53); (R): >30 (0) μM (parentheses: SEM)[2]
72-hour WST viability, MDA-MB-231IC50 (SEM) Racemate: 0.82 (0.02); (S): 1.17 (0.78); (R): 22.02 (2.43) μM (parentheses: SEM)[2]
72-hour WST viability, PANC1IC50 (SEM) Racemate: 1.514 (0.6503); (S): 1.69 (0.74); (R): 24.87 (5.13) μM (parentheses: SEM)[2]
72-hour WST viability, ASPC1IC50 (SEM) Racemate: 14.28 (3.50); (S): 8.16 (6.04); (R): >30 (0) μM (parentheses: SEM)[2]

Literature-Reported Treatment Conditions

Treatment concentration
0.1–30 μM for the dose-response experiment
Exposure duration
72 h (3 days)
Method
WST viability assay; compound or vehicle added the day after plating
Vehicle
DMSO control; final percentage not specified in the selected proliferation method
Co-treatment
Racemate and each enantiomer tested separately
Reported limits
Final DMSO percentage and detailed concentration series beyond the stated range are not supplied in the selected method.
Methods and source locations

Compound reported in the paper: YK-4-279; Compound label in the paper: Racemic YK-4-279 with resolved (S)- and (R)-YK-4-279 comparators

Racemate results apply at compound level; enantiomer-specific results must retain their (S)/(R) labels. No lot validation.

Fig. 4A–C; Table 1; Results: YK-4-279 demonstrates enantiospecific cellular effects; Methods: Cellular Proliferation Assays; Discussion

WST viability IC50 across seven ESFT lines after 72 h: Dose-response fits; Results state three experiments in triplicate — Table 1 ESFT rows; Fig. 4B; Results: enantiospecific cellular effects

72-hour WST viability, TC32: Sigmoidal dose-response fit; experiments repeated three times in triplicate — Table 1, TC32 row; Fig. 4A–C; Methods: Cellular Proliferation Assays

72-hour WST viability, TC71: Sigmoidal dose-response fit; experiments repeated three times in triplicate — Table 1, TC71 row; Fig. 4A–C; Methods: Cellular Proliferation Assays

72-hour WST viability, RDES: Sigmoidal dose-response fit; experiments repeated three times in triplicate — Table 1, RDES row; Fig. 4A–C; Methods: Cellular Proliferation Assays

72-hour WST viability, SKES: Sigmoidal dose-response fit; experiments repeated three times in triplicate — Table 1, SKES row; Fig. 4A–C; Methods: Cellular Proliferation Assays

72-hour WST viability, MMH-ES-1: Sigmoidal dose-response fit; experiments repeated three times in triplicate — Table 1, MMH-ES-1 row; Fig. 4A–C; Methods: Cellular Proliferation Assays

72-hour WST viability, STA-ET 7.2: Sigmoidal dose-response fit; experiments repeated three times in triplicate — Table 1, STA-ET 7.2 row; Fig. 4A–C; Methods: Cellular Proliferation Assays

72-hour WST viability, A4573: Sigmoidal dose-response fit; experiments repeated three times in triplicate — Table 1, A4573 row; Fig. 4A–C; Methods: Cellular Proliferation Assays

72-hour WST viability, PC3: Sigmoidal dose-response fit; experiments repeated three times in triplicate — Table 1, PC3 row; Fig. 4A–C; Methods: Cellular Proliferation Assays

72-hour WST viability, MCF7: Sigmoidal dose-response fit; experiments repeated three times in triplicate — Table 1, MCF7 row; Fig. 4A–C; Methods: Cellular Proliferation Assays

72-hour WST viability, MDA-MB-231: Sigmoidal dose-response fit; experiments repeated three times in triplicate — Table 1, MDA-MB-231 row; Fig. 4A–C; Methods: Cellular Proliferation Assays

72-hour WST viability, PANC1: Sigmoidal dose-response fit; experiments repeated three times in triplicate — Table 1, PANC1 row; Fig. 4A–C; Methods: Cellular Proliferation Assays

72-hour WST viability, ASPC1: Sigmoidal dose-response fit; experiments repeated three times in triplicate — Table 1, ASPC1 row; Fig. 4A–C; Methods: Cellular Proliferation Assays

In Vivo Studies

In neonatal mice, a single P5 intravitreal injection of 70 nL of 150 μmol/L YK-4-279 produced approximately 40% fewer hyaloid vessels at P7 than vehicle treatment (n = 7 in the figure; P < 0.05). This demonstrates accelerated developmental vessel regression under the tested conditions. [3]

Neonatal mouse hyaloid vessel regression

Animal study · Wild-type neonatal mice, P5 injection and P7 hyaloid-vessel assessment; both sexes included in study [3]

A single intravitreal YK-4-279 treatment accelerated hyaloid vessel regression relative to vehicle-injected littermate controls. This is a developmental vascular endpoint and does not by itself establish the molecular target, retinal disease efficacy or visual-function benefit.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
Number of hyaloid vessels crossing a 50%-diameter outline at P7Relative vessel-number reduction ∼40% reduction versus vehicle; n = 7 in Fig. 3B; P < 0.05[3]

Conditions shared by the study groups

Route
Intravitreal
Frequency
Single injection at P5
Treatment course
Assessment at P7
Vehicle
0.9% sterile saline vehicle control
Study groups and reported outcomes
Group / doseComparatorObserved resultReference
YK-4-279 versus saline vehicle
70 nL of 150 μmol/L YK-4-279; estimated final vitreous concentration ∼10 μmol/L		Vehicle-injected littermate controls∼40% fewer hyaloid vessels; n = 7 in Fig. 3B; P < 0.05, two-tailed Student’s t test; error bars SD[3]
YK-4-279 versus saline vehicle
Model: Wild-type neonatal mice; hyaloid vessels
Reported limits: n is reported for the comparison; randomization and sex-stratified results are not specified in the selected experiment. No supplier-to-arm assignment.
Methods and source locations

Compound reported in the paper: YK-4-279

Restricted to the P5–P7 hyaloid experiment and its stated injection solution; no systemic dose extrapolation.

Fig. 3A–B and caption; Results: A Pharmacological Inhibitor of ETS Transcription Factors; Methods: Mice, Hyaloid Vessel Dissection and Quantification, Intravitreal Injection of YK-4-279 in Neonatal Mice

Number of hyaloid vessels crossing a 50%-diameter outline at P7: Blinded flat-mount vessel counting; two-tailed Student’s t test; Fig. 3 error bars SD — Fig. 3A–B and caption; Results: A Pharmacological Inhibitor; Methods: Hyaloid Vessel Dissection and Quantification

YK-4-279 versus saline vehicle · Fig. 3A–B and caption; Results: A Pharmacological Inhibitor of ETS Transcription Factors; Methods: Mice, Hyaloid Vessel Dissection and Quantification, Intravitreal Injection of YK-4-279 in Neonatal Mice

Specifications

Manufacturer Adooq Bioscience
Actions Inhibitor
CAS Number 1037184-44-3
Applications RHA inhibitor
Formula C17H13Cl2NO4
Molecular Weight 366.2
SMILES
COC1=CC=C(C=C1)C(=O)CC2(C3=C(C=CC(=C3NC2=O)Cl)Cl)O

Storage & Solubility

In Vitro Solubility

Reported Solubility

SolventReported Solubility
DMSO 66 mg/mL (180.23 mM)
Water Insoluble
Ethanol Warmed: 46 mg/mL (125.61 mM)

Preparing Stock Solutions

Stock preparation is unavailable for this product molecular weight.

Calculated stock concentrations do not establish solvent solubility. Refer to the reported solubility data for experimental guidance.

Storage

Store powder at -20°C, keep desiccated.
In powder form, the chemical is stable for 36 months.
In solution, store at -20°C and use within 1 month to prevent loss of potency. Aliquot to avoid multiple freeze/thaw cycles.

Research References

  1. [1] Erkizan HV, Kong Y, Merchant M, et al. A small molecule blocking oncogenic protein EWS-FLI1 interaction with RNA helicase A inhibits growth of Ewing's sarcoma. Nature medicine (2009). PMID: 19584866 DOI: 10.1038/nm.1983 Source material
  2. [2] Barber-Rotenberg JS, Selvanathan SP, Kong Y, et al. Single enantiomer of YK-4-279 demonstrates specificity in targeting the oncogene EWS-FLI1. Oncotarget (2012). PMID: 22383402 DOI: 10.18632/oncotarget.454 Source material
  3. [3] Schafer CM, Gurley JM, Kurylowicz K, et al. An inhibitor of endothelial ETS transcription factors promotes physiologic and therapeutic vessel regression. Proceedings of the National Academy of Sciences of the United States of America (2020). PMID: 33020273 DOI: 10.1073/pnas.2015980117 Source material

Publications

1 publication citing this product

  1. Christopher M Schafer, .et al. , Proc Natl Acad Sci U S A, 2020, Oct 20;117(42):26494-26502 PMID: 33020273

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