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Chemical Structure| 50995-74-9 Chemical Structure| 50995-74-9

Structure of 7ACC1
CAS No.: 50995-74-9

Chemical Structure| 50995-74-9

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7ACC1 selectively interfere with lactate fluxes in the lactate-rich tumor microenvironment and inhibits lactate influx but not efflux in tumor cells expressing MCT1 and MCT4 transporters.

Synonyms: DEAC; Coumarin D 1421; 7-Diethylamino-2-oxo-2H-chromen-3-carboxylic Acid

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Product Citations

Product Citations

Haroon, Muhammad ; Sultana, Sharmin ; Najibi, Seyedeh A ; Wang, Emily T ; Michaelson, Abbey ; Al Muied, Pranto SM , et al.

Abstract: The imidazoquinoline family of immune cell agonists has long demonstrated moderate anticancer immunogenic effects by activating tumoricidal immune cells and depleting immunosuppressive cells within the tumor microenvironment. At a molecular level, we have also established that several imidazoquinolines traffic from within cancer cells to the extracellular space via P-glycoprotein (P-gp)-mediated efflux, a process commonly upregulated as multidrug-resistant (MDR) cancers acquire chemoresistance. However, imidazoquinoline efflux has never been deliberately enhanced to exploit this process. This study pioneers efforts to optimize imidazoquinoline efflux, ultimately balancing immunogenic potency alongside functional efflux susceptibility. Starting from an established imidazoquinoline scaffold previously optimized for potency, efflux was significantly enhanced by elaborating the N1 benzylic position with amide- and sulfonamide-linked affinity fragments consisting of empirically established substrates as well as computationally predicted binders. Lead compounds were identified from this series that exhibited enhanced efflux with functional retention of agonism. Similar to the parent imidazoquinoline scaffold, leads had limited direct cytotoxicity in both treatment-naive and MDR B16 melanoma models and did not significantly affect the efficacy or trafficking of the chemotherapeutic doxorubicin. Efflux-enhanced imidazoquinolines were preferentially expelled from MDR-B16 cells relative to treatment-naive cells, resulting in immunogenicity that was enhanced as a consequence of the acquired MDR phenotype. Because enhanced P-gp-mediated efflux is common to most MDR cancer types, we envision that these results could inspire the design of immunotherapeutic drugs with mechanisms of action that are broadly enhanced in MDR cancers that have failed treatment or acquired resistance to chemotherapeutics.

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Product Details of 7ACC1

CAS No. :50995-74-9
Formula : C14H15NO4
M.W : 261.27
SMILES Code : O=C(C(C1=O)=CC2=C(O1)C=C(N(CC)CC)C=C2)O
Synonyms :
DEAC; Coumarin D 1421; 7-Diethylamino-2-oxo-2H-chromen-3-carboxylic Acid
MDL No. :MFCD00068721
InChI Key :WHCPTFFIERCDSB-UHFFFAOYSA-N
Pubchem ID :659294

Safety of 7ACC1

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of 7ACC1

RTK

Isoform Comparison

Biological Activity

Description
7ACC1 (DEAC; Coumarin D 1421; D 1421) selectively interferes with lactate fluxes within the lactate-rich tumor microenvironment. It inhibits lactate influx but not efflux in tumor cells expressing MCT1 and MCT4 transporters, with an IC50 value of 0.86 µM for lactate uptake inhibition[1].

In Vitro:

Cell Line
Concentration Treated Time Description References
HEK-293 cells 10 μM 9 min Validate the effect of 7ACC1 as an MPC inhibitor J Biol Chem. 2022 Feb;298(2):101554.
Hepatocytes 10 μM 3 h Evaluate the effect of 7ACC1 on hepatocyte glucose production J Biol Chem. 2022 Feb;298(2):101554.
HUVECs 10 µM 24 h To evaluate the effect of 7ACC1 on the proliferation and migration of HUVECs. Results showed that 7ACC1 significantly attenuated cell proliferation and migration. Cancer Cell Int. 2019 Jun 28;19:170.
786-O cells 10 µM 24 h To evaluate the effect of 7ACC1 on the proliferation, migration, and invasion of 786-O cells. Results showed that 7ACC1 significantly attenuated cell proliferation, migration, and invasion. Cancer Cell Int. 2019 Jun 28;19:170.
4T1 cells 0.1, 0.01, 0.001 mM 24 h Evaluate the effect of 7acc1 on 4T1 cells, results showed that 7acc1 treatment significantly enhanced the cytotoxicity of NK cells. Cancer Med. 2018 Sep;7(9):4690-4700.

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice High fat diet-induced obese (DIO) mice Intraperitoneal injection 0.3 mg/kg 4 weeks Block propionate transport and abolish the therapeutic effects of L. reuteri and CQA co-treatment on obesity-associated metabolic disorders Microbiome. 2022 Dec 15;10(1):226
BALB/c mice Breast cancer model Intraperitoneal injection 0.3, 0.03, 0.003 mg/kg Once daily for 7 days Evaluate the effect of 7acc1 on tumor growth, results showed that 7acc1 significantly inhibited tumor growth and enhanced the cytotoxicity of NK cells. Cancer Med. 2018 Sep;7(9):4690-4700.

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

3.83mL

0.77mL

0.38mL

19.14mL

3.83mL

1.91mL

38.27mL

7.65mL

3.83mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1

References

 

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