2,5-Dimethyl-celecoxib

• CAS: 457639-26-8
• Catalog Number: ACM457639268
• Category: Main Products
• Molecular Weight: 395.40
• Molecular Formula: C₁₈H₁₆F₃N₃O₂S
• Synonyms: 2,5-dimethylcelecoxib, 457639-26-8, 2,5-dimethyl-celecoxib, Dimethyl Celecoxib, AGN-PC-00BARL, SureCN2228663, CHEMBL2163630, 4-[5-(2,5-dimethylphenyl)-3-(trifluoromethyl)pyrazol-1-yl]benzenesulfonamide, 4-(5-(2,5-Dimethylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide\r\n, 4-[5-(2,5-dimethylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]-benzenesulfonamide
• IUPAC Name: 4-[5-(2,5-dimethylphenyl)-3-(trifluoromethyl)pyrazol-1-yl]benzenesulfonamide
• SMILES: CC1=CC(=C(C=C1)C)C2=CC(=NN2C3=CC=C(C=C3)S(=O)(=O)N)C(F)(F)F
• InChI Key: NTFOSUUWGCDXEF-UHFFFAOYSA-N
• Appearance: solid
• Exact Mass: 395.09200
• H-Bond Acceptor: 7
• H-Bond Donor: 1

Case Study

2,5-Dimethyl-celecoxib as a COX-2-Independent Antitumor Agent for Hematologic Malignancies

Sobolewski, Cyril, et al. The Journal of Pharmacology and Experimental Therapeutics 355.2 (2015): 308-328.

2,5-Dimethyl-celecoxib (DMC), a celecoxib analog lacking cyclooxygenase-2 (COX-2) inhibitory activity, represents a promising alternative for cancer therapy. This study investigated the effects of DMC on human leukemia cell lines (U937, Jurkat, K562, Raji, Hel) compared to celecoxib, elucidating mechanisms of growth inhibition and apoptosis.
DMC was evaluated for cell proliferation inhibition, apoptosis induction, mitochondrial membrane potential, cell cycle progression, and protein expression changes. ER stress and calcium release were assessed using Fluo-4 AM staining and real-time PCR.
Key Results:
· DMC inhibited growth of all tested leukemia cell lines more potently than celecoxib: in U937 cells, 40 μM DMC achieved 85.7% growth inhibition at 48 h vs. 59.5% for celecoxib, with apoptosis induction at 20 μM for DMC vs. 60 μM for celecoxib.
· Apoptosis was caspase-dependent (partial reversal by Z-Vad) but necroptosis-independent (necrostatin-1 had no effect), with cleavage of caspases-3, -7, -8, and -9 observed from 20 μM DMC.
· DMC triggered rapid downregulation of the antiapoptotic protein Mcl-1 within 15 min, preceding loss of mitochondrial membrane potential (33.7% cells with low ΔΨm at 2 h). Mcl-1 downregulation occurred via translational inhibition, independent of proteasome or mRNA changes.
· DMC induced ER stress, evidenced by increased mRNA of ATF4, CHOP, and GRP78 at 8 h, with decreased ER calcium content and reduced GRP78 protein expression.
· Cell cycle analysis revealed dual effects: early mitotic delay (prophase accumulation at 4 h, associated with survivin downregulation and cyclin B1 accumulation) followed by G0/G1 arrest at 24 h, with downregulation of c-Myc and cyclin D1, and upregulation of p27.

2,5-Dimethyl-celecoxib as a COX-2-Independent Antiaging Agent Targeting Insulin and TOR Signaling

Wu, Qi, et al. Journals of Gerontology Series A: Biomedical Sciences and Medical Sciences 72.10 (2017): 1334-1341.

2,5-Dimethyl-celecoxib (DMC), a celecoxib derivative lacking COX-2 activity, retains beneficial antitumor effects but its antiaging potential was unexplored. This study evaluated DMC in Drosophila melanogaster using a chemically defined holistic medium to assess lifespan extension, healthspan, and mechanistic involvement of insulin/IGF-1 signaling (IIS) and TOR pathways. DMC was administered to adult flies at various concentrations (0.05-10 μM).
Key Results:
· DMC (0.5 μM) extended mean lifespan by 10.2% in females (66.9→73.7 days, p<0.0001) and 9.1% in males (41.9→45.7 days, p=0.01), with a characteristic non-monotonic dose-response. Lifespan extension was independent of dietary restriction, as DMC increased lifespan across all amino acid concentrations tested.
· Remarkably, lifespan benefits were equally effective when DMC was administered only during early life (first 20 days) or late life (from day 42 onward), indicating durable slowing of aging processes rather than acute risk reduction.
· DMC improved healthspan: it increased female fecundity at intermediate/high amino acid levels, enhanced male climbing ability in mid-to-late life, reduced intestinal permeability (Smurf rate decreased from ~35% to ~20% at day 40), and decreased gut bacterial load (Lactobacilli, Acetobacteriaceae, Enterobacteriaceae) in aged flies.
· DMC enhanced stress tolerance: survival under starvation increased 15.1% (females) and 7.3% (males), with elevated triglyceride stores; heat tolerance improved 18.5% (females) and 8.8% (males). No protection was observed against oxidative stress (paraquat, H2O2) or desiccation.

2,5-Dimethyl-celecoxib Attenuates Post-Infarct Cardiac Remodeling by Modulating Macrophage Dynamics

Kishigami, Takehiro, et al. Journal of Pharmacological Sciences 154.2 (2024): 97-107.

Excessive and prolonged inflammation after myocardial infarction (MI) drives adverse cardiac remodeling and heart failure progression. This study investigated 2,5-Dimethyl-celecoxib (DM-C) in a cryoinjury-induced MI (CMI) mouse model and in peritoneal macrophages. Mice received DM-C (1000 ppm in feed) starting 3 days before CMI. In vitro, LPS/IFN-γ-stimulated peritoneal macrophages were treated with DM-C (20 μM) to evaluate phagocytosis (latex beads), proliferation, and differentiation.
Key Results:
· DM-C preserved cardiac function: LV ejection fraction decline was attenuated at day 14 post-CMI (vehicle: ~35% vs. DM-C: ~45%). Fibrotic area was reduced by ~25%.
· DM-C accelerated resolution of inflammation: pro-inflammatory cytokines (IL-1β, IL-6, TNF, MCP-1) were significantly downregulated at the infarct site by day 7, while anti-inflammatory cytokines (IL-10, TGF-β1) were unaffected.
· DM-C induced transient macrophage accumulation: CD68+ macrophage numbers peaked sharply at day 3 (vs. days 3-5 in controls) and rapidly declined by day 7, without altering M1/M2 polarization ratios.
· DM-C enhanced clearance capacity: In vitro, DM-C increased the proportion of CD68+ macrophages (from ~35% to ~55%) by promoting monocyte-to-macrophage differentiation, not proliferation. Total phagocytic capacity (double-positive CD68+/bead+ cells) increased, while per-cell phagocytic efficiency was unchanged.
· DM-C accelerated necrotic cell removal: HMGB-1-positive area at the infarct site was significantly reduced by day 7, indicating faster debris clearance.

Custom Q&A

What is the molecular formula of 2,5-Dimethyl-celecoxib?

The molecular formula is C18H16F3N3O2S.

What are the synonyms for 2,5-Dimethyl-celecoxib?

The synonyms include 457639-26-8, 2,5-dimethylcelecoxib, 2,5-Dimethyl Celecoxib, and 2,5-dimethyl-celecoxib.

What is the molecular weight of 2,5-Dimethyl-celecoxib?

The molecular weight is 395.4 g/mol.

When was 2,5-Dimethyl-celecoxib created?

It was created on October 26, 2006.

When was 2,5-Dimethyl-celecoxib last modified?

It was last modified on October 21, 2023.

What is the IUPAC name of 2,5-Dimethyl-celecoxib?

The IUPAC name is 4-[5-(2,5-dimethylphenyl)-3-(trifluoromethyl)pyrazol-1-yl]benzenesulfonamide.

What is the InChI of 2,5-Dimethyl-celecoxib?

The InChI is InChI=1S/C18H16F3N3O2S/c1-11-3-4-12(2)15(9-11)16-10-17(18(19,20)21)23-24(16)13-5-7-14(8-6-13)27(22,25)26/h3-10H,1-2H3,(H2,22,25,26).

What is the InChIKey of 2,5-Dimethyl-celecoxib?

The InChIKey is NTFOSUUWGCDXEF-UHFFFAOYSA-N.

What is the canonical SMILES of 2,5-Dimethyl-celecoxib?

The canonical SMILES is CC1=CC(=C(C=C1)C)C2=CC(=NN2C3=CC=C(C=C3)S(=O)(=O)N)C(F)(F)F.

What is the CAS number of 2,5-Dimethyl-celecoxib?

The CAS number is 457639-26-8.