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Chemical Structure| 1391934-98-7 Chemical Structure| 1391934-98-7

Structure of FIDAS-5
CAS No.: 1391934-98-7

Chemical Structure| 1391934-98-7

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FIDAS-5 is a potent and orally active methionine S-adenosyltransferase 2A (MAT2A) inhibitor with an IC50 of 2.1 μM. FIDAS-5 effectively competes against S-adenosylmethionine (SAM) for MAT2A binding. FIDAS-5 has anticancer activities[1].

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Product Citations

Product Citations

Maekawa, Hiroshi ; Zhou, Yalu ; Aoi, Yuki ; Fain, Margaret E ; Kaminski, Dorian S ; Kong, Hyewon , et al.

Abstract: Clinically, blockade of renal glucose resorption by sodium–glucose cotransporter 2 (SGLT2) inhibitors slows progression of kidney disease, yet the underlying mechanisms are not fully understood. We hypothesized that altered renal metabolites underlie observed kidney protection when SGLT2 function is lost. S-adenosylmethionine (SAM) levels were increased in kidneys from mice lacking SGLT2 function on a diabetogenic high-fat diet (SPHFD) compared with WT mice fed HFD. Elevated SAM in SPHFD was associated with improved kidney function and decreased expression of NF-κB pathway–related genes. Injured proximal tubular cells that emerged under HFD conditions in WT mice and humans consistently showed reduction in expression of the SAM synthetase Mat2a/MAT2A, while MAT2A inhibition, which reduces SAM production, abrogated kidney protection in SPHFD mice. Histone H3 lysine 27 (H3K27) repressive trimethylation of NF-κB–related genes was increased in SPHFD, consistent with SAM’s role as a methyl donor. Our data support a model whereby SGLT2 loss enhances SAM levels within the kidney, leading to epigenetic repression of inflammatory genes and kidney protection under metabolic stress.

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Product Details of FIDAS-5

CAS No. :1391934-98-7
Formula : C15H13ClFN
M.W : 261.72
SMILES Code : CNC1=CC=C(/C=C/C2=C(F)C=CC=C2Cl)C=C1
MDL No. :MFCD32671894
InChI Key :KXVXICBOMOGFMH-JXMROGBWSA-N
Pubchem ID :57521314

Safety of FIDAS-5

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P280-P301+P312-P302+P352-P305+P351+P338

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
U251-MG cells 10 μM 10 days To evaluate the effect of FIDAS-5 on tumorsphere formation, results showed that FIDAS-5 significantly reduced the number and diameter of tumorspheres and decreased the expression levels of SOX2 and OCT4. Life Med. 2023 Nov 23;2(6):lnad048
U87-MG cells 10 μM 10 days To evaluate the effect of FIDAS-5 on tumorsphere formation, results showed that FIDAS-5 significantly reduced the number and diameter of tumorspheres and decreased the expression levels of SOX2 and OCT4. Life Med. 2023 Nov 23;2(6):lnad048
OPM2 cells 250 nM 4 days Inhibited cell proliferation, reduced BrdU incorporation, and caused G0/G1 and G2 phase cell cycle arrest Haematologica. 2024 Jan 1;109(1):256-271
JJN3 cells 250 nM 4 days Inhibited cell proliferation, reduced BrdU incorporation, and caused G0/G1 and G2 phase cell cycle arrest Haematologica. 2024 Jan 1;109(1):256-271
Hep3B cells 1 μM 72 hours Induced cell cycle arrest and DNA damage, leading to cellular senescence Nat Cancer. 2024 Jan;5(1):131-146
Huh7 cells 5 μM 72 hours Induced cell cycle arrest and DNA damage, leading to cellular senescence Nat Cancer. 2024 Jan;5(1):131-146
mouse HL-1 cardiomyocytes 5 μM 24-30 hours Inhibited MAT2A activity, significantly suppressing ferroptosis induced by cystine deprivation Nat Commun. 2024 Oct 17;15(1):8971
human OS-RC-2 renal carcinoma cells 5 μM 14-18 hours Inhibited MAT2A activity, significantly suppressing ferroptosis induced by cystine deprivation Nat Commun. 2024 Oct 17;15(1):8971
human HT1080 fibrosarcoma cells 5 μM 10-14 hours Inhibited MAT2A activity, significantly suppressing ferroptosis induced by cystine deprivation Nat Commun. 2024 Oct 17;15(1):8971
mouse embryonic fibroblast (MEF) cells 5 μM 8-12 hours Inhibited MAT2A activity, significantly suppressing ferroptosis induced by cystine deprivation or blockage of cystine uptake Nat Commun. 2024 Oct 17;15(1):8971

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
C57BL/KaLwRij mice 5TGM1 model Intraperitoneal injection 20 mg/kg Three times a week for 28 days Significantly reduced tumor burden, decreased percentage of eGFP-positive cells and bone marrow plasmacytosis Haematologica. 2024 Jan 1;109(1):256-271
Nude mice Huh7 and Hep3B xenograft models Intraperitoneal injection 10 mg/kg Once daily for 7 days Inhibited tumor growth and induced tumor cell senescence Nat Cancer. 2024 Jan;5(1):131-146
Nude mice OS-RC-2 tumor xenograft model Intragastrically 20 mg/kg Every 2 days for 12 days Inhibited MAT2A activity, attenuating IKE-induced tumor growth suppression Nat Commun. 2024 Oct 17;15(1):8971
NSG mice Orthotopic GBM xenografts Intraperitoneal injection 40 mg/kg Daily treatment To evaluate the effect of FIDAS-5 on tumor growth, results showed that FIDAS-5 significantly inhibited the growth of xenografts and conferred a significant survival benefit relative to the vehicle control. Life Med. 2023 Nov 23;2(6):lnad048

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

3.82mL

0.76mL

0.38mL

19.10mL

3.82mL

1.91mL

38.21mL

7.64mL

3.82mL

References

 

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