Fig. 1 · Structure

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EHT 1864

Cat. No. A13886 CAS 754240-09-0

Rac family GTPase inhibitor

EHT 1864 is an antiproliferative chemical shown to inhibit Rac family GTPases.

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Publications for EHT 1864

2 publications citing this product

  1. Natalie J Jooss, .et al. , J Thromb Haemost, 2023, Aug;21(8):2260-2267 PMID: 37150294
  2. Kakoki M, .et al. , JCI Insight, 2019, Jun 20;4(12) PMID: 31217360

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Biological Activity

Target & Activity

Target Activity Value
Rac1 Kd 40 nM
Rac1b Kd 50 nM
Rac2 Kd 60 nM
Rac3 Kd 250 nM

In Vitro Studies

EHT1864 (20 or 50 μM, 72 h) increased Annexin-V-positive apoptosis in BT-474, T47D, MDA-MB-415 and CAMA-1 breast cancer cells. Responses were larger in BT-474 and T47D. These cellular effects do not establish exclusive Rac dependence. [1]

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

Annexin-V apoptosis response across four breast cancer cell lines

Cell-based study · Human BT-474, T47D, MDA-MB-415 and CAMA-1 breast cancer cells [1]

EHT1864 increased Annexin-V-positive apoptosis in all four lines at 20 and 50 μM after 72 h, with a larger response in BT-474 and T47D. These are cellular treatment concentrations, not biochemical IC50 values. Pharmacological response alone does not prove exclusive Rac dependence.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
Annexin-V-positive cells, including floating and adherent populationsapoptosis response Dose-related increases in Annexin-V-positive cells across four lines; Figure 1D caption defines *p < 0.0001 by Bonferroni post-hoc test vs. control unless bracketed. No dose-specific significance assignment or percentage estimated here.[1]

Literature-Reported Treatment Conditions

Treatment concentration
0, 20 or 50 μM EHT1864 (Figure 1D)
Exposure duration
72 h
Method
Cells cultured in DMEM with 10% FBS; floating and trypsin-displaced adherent cells analyzed together
Co-treatment
No cotreatment assigned to the EHT1864 dose-response groups. Separate assay-control wells received 5 μM BKM120 during the final 12 h; negative controls did not.
Reported limits
Vehicle and number of independent biological replicates/error-bar definition for Figure 1D are not specified in its caption or selected apoptosis methods; no values or n inferred.
Methods and source locations

Compound reported in the paper: EHT1864; Compound label in the paper: Diaxonhit-provided EHT1864; salt form unspecified

Cellular EHT1864 response in these four lines, without catalog-lot, salt-specific, clinical or universal Rac-selectivity claims.

Figure 1D and caption; Results first subsection; Methods: Cell lines and reagents, Apoptosis assay, Statistical analyses

Annexin-V-positive cells, including floating and adherent populations: ApoScreen Annexin Apoptosis kit with flow cytometry; ANOVA and Bonferroni comparison adjustment; no numerical percentages transcribed from bars — Figure 1D and caption; Results first subsection; Methods: Cell lines and reagents, Apoptosis assay, Statistical analyses

In Vivo Studies

In male ELMO1-hypermorphic Akita diabetic mice, EHT1864 in drinking water (40 mg/L for 4 weeks) improved left ventricular ejection fraction and reduced cardiac Rac1 activity and ROS indicators. Benefit was partial: GSH/GSSG was unchanged, and the chamber-dimension panels did not show significant improvement. [2]

Partial cardiac improvement in ELMO1-hypermorphic diabetic mice

Animal study · Male C57BL/6J-background Elmo1 H/H Ins2 Akita/+ (HHA+) mice, treated from age 12 to 16 weeks [2]

EHT1864 increased LVEF and reduced cardiac Rac1 activity and ROS indicators relative to untreated HHA+ mice. Benefit was partial: Figure 6C/D does not mark a significant improvement in LVPWd or LVIDd for EHT1864, and GSH/GSSG was not significantly changed. Separate VAS3947 and Nox4-deletion comparators support additional Rac-independent contributions; they were not combination treatments. Untreated HHA+ data were reused from earlier experiments within this paper.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
Left ventricular ejection fraction (LVEF)direction and significance Increased vs. untreated HHA+; *P < 0.05; n=9 EHT1864, n=14 untreated; mean ± SEM[2]
Cardiac Rac1-GTP, superoxide indicator 2-OH-E+ and H2O2 releasedirection and significance Each decreased vs. untreated HHA+ (*P < 0.05); Rac1 n=6/group, 2-OH-E+ n=5/group, H2O2 n=6/group; mean ± SEM[2]
Left ventricular wall thickness, internal diameter and GSH/GSSG ratiolimiting results No significance marker for EHT1864 in Figure 6C/D; no significant GSH/GSSG change in Figure 6H. C/D: n=9 EHT1864, 14 untreated; H: n=6/group; mean ± SEM[2]

Conditions shared by the study groups

Route
Oral
Frequency
Provided in drinking water; individual consumption not reported in selected description
Treatment course
4 weeks from age 12 weeks
Vehicle
Drinking water
Study groups and reported outcomes
Group / doseComparatorObserved resultReference
EHT1864 vs. untreated HHA+
40 mg/L drinking water
Untreated HHA+ mice; historical within-paper baseline data reusedPartial functional improvement, lower Rac1/ROS readouts, with unchanged GSH/GSSG and no significant chamber-dimension improvement marked in Figure 6C/D[2]
EHT1864 vs. untreated HHA+
Model: Male HHA+ diabetic mice on C57BL/6J background
Reported limits: No mg/kg/day conversion; salt form and product lot not specified. Sample sizes differ by endpoint.
Methods and source locations

Compound reported in the paper: EHT1864; Compound label in the paper: Adooq EHT1864; salt form unspecified

Reported EHT1864 effects in this male diabetic mouse model; no form-specific equivalence or clinical efficacy claim.

Figure 6 A–K and caption; Results: Pivotal role of NADPH oxidases; Methods: Mice, Echocardiography, Statistics; Supplemental Methods pp. 17–18

Left ventricular ejection fraction (LVEF): Echocardiography in conscious mice; one-way ANOVA with Tukey-Kramer Honestly Significant Differences test — Figure 6B and caption; Methods: Echocardiography, Statistics

Cardiac Rac1-GTP, superoxide indicator 2-OH-E+ and H2O2 release: PAK-PBD pulldown/anti-Rac1 immunoblot; HPLC oxidation-product assay; H2O2 release assay described in Supplemental Methods — Figure 6E–G and caption; Supplemental Methods: Rac activity assay and Western blotting, HPLC analysis, Measurement of biological parameters

Left ventricular wall thickness, internal diameter and GSH/GSSG ratio: Echocardiography and glutathione assay; comparisons as in Figure 6 caption — Figure 6C/D/H and caption; Results paragraph beginning The administered dose of EHT1864

EHT1864 vs. untreated HHA+ · Figure 6 A–K and caption; Results: Pivotal role of NADPH oxidases; Methods: Mice, Echocardiography, Statistics; Supplemental Methods pp. 17–18

Specifications

Manufacturer Adooq Bioscience
Actions Inhibitor
CAS Number 754240-09-0
Applications Rac family GTPase inhibitor
Formula C25H27F3N2O4S.2HCl
Molecular Weight 581.47
SMILES
C1COCCN1CC2=CC(=O)C(=CO2)OCCCCCSC3=C4C=CC(=CC4=NC=C3)C(F)(F)F.Cl.Cl

Storage & Solubility

In Vitro Solubility

Reported Solubility

SolventReported Solubility
DMSO Warmed: 90 mg/mL (154.77 mM)
Water 90 mg/mL (154.77 mM)
Ethanol Insoluble

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] Hampsch RA, Shee K, Bates D, et al. Therapeutic sensitivity to Rac GTPase inhibition requires consequential suppression of mTORC1, AKT, and MEK signaling in breast cancer. Oncotarget (2017). PMID: 28423521 DOI: 10.18632/oncotarget.15586 Source material
  2. [2] Kakoki M, Bahnson EM, Hagaman JR, et al. Engulfment and cell motility protein 1 potentiates diabetic cardiomyopathy via Rac-dependent and Rac-independent ROS production. JCI insight (2019). PMID: 31217360 DOI: 10.1172/jci.insight.127660 Source material

Publications

2 publications citing this product

  1. Natalie J Jooss, .et al. , J Thromb Haemost, 2023, Aug;21(8):2260-2267 PMID: 37150294
  2. Kakoki M, .et al. , JCI Insight, 2019, Jun 20;4(12) PMID: 31217360

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