Molecule Information

General Information of the Molecule (ID: Mol02100)

• Name: Prostaglandin G/H synthase 2 (Cox-2) ,Mus musculus
• Synonyms: Prostaglandin G/H synthase 2 (EC 1.14.99.1) (Cyclooxygenase-2) (COX-2) (Glucocorticoid-regulated inflammatory cyclooxygenase) (Gripghs) (Macrophage activation-associated marker protein P71/73) (PES-2) (PHS II) (Prostaglandin H2 synthase 2) (PGH synthase 2) (PGHS-2) (Prostaglandin-endoperoxide synthase 2) (TIS10 protein); Ptgs2; Cox-2; Cox2; Pghs-b; Tis10
• Molecule Type: Protein
• Gene Name: Cox-2
• Gene ID: 19225
• Location: Chromosome 1: 149,975,782-149,983,978 forward strand
• Sequence:
  MLFRAVLLCAALGLSQAANPCCSNPCQNRGECMSTGFDQYKCDCTRTGFYGENCTTPEFL
  TRIKLLLKPTPNTVHYILTHFKGVWNIVNNIPFLRSLIMKYVLTSRSYLIDSPPTYNVHY
  GYKSWEAFSNLSYYTRALPPVADDCPTPMGVKGNKELPDSKEVLEKVLLRREFIPDPQGS
  NMMFAFFAQHFTHQFFKTDHKRGPGFTRGLGHGVDLNHIYGETLDRQHKLRLFKDGKLKY
  QVIGGEVYPPTVKDTQVEMIYPPHIPENLQFAVGQEVFGLVPGLMMYATIWLREHNRVCD
  ILKQEHPEWGDEQLFQTSRLILIGETIKIVIEDYVQHLSGYHFKLKFDPELLFNQQFQYQ
  NRIASEFNTLYHWHPLLPDTFNIEDQEYSFKQFLYNNSILLEHGLTQFVESFTRQIAGRV
  AGGRNVPIAVQAVAKASIDQSREMKYQSLNEYRKRFSLKPYTSFEELTGEKEMAAELKAL
  YSDIDVMELYPALLVEKPRPDAIFGETMVELGAPFSLKGLMGNPICSPQYWKPSTFGGEV
  GFKIINTASIQSLICNNVKGCPFTSFNVQDPQPTKTATINASASHSRLDDINPTVLIKRR
  STEL
• 3D-structure: PDB ID: 8HEZ; Classification: Transport protein; Method: Electron microscopy; Resolution: 2.80 Å
• Function: Electrogenic Na(+)-coupled sugar simporter that actively transports D-glucose at the plasma membrane, with a Na(+) to sugar coupling ratio of 1:1. Transporter activity is driven by a transmembrane Na(+) electrochemical gradient set by the Na(+)/K(+) pump. Has a primary role in D-glucose reabsorption from glomerular filtrate across the brush border of the early proximal tubules of the kidney.
• Uniprot ID: PGH2_MOUSE
• Ensembl ID: ENSMUSG00000032487

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: 9989
Family: Muridae
Genus: Mus
Species: Mus musculus

Type(s) of Resistant Mechanism of This Molecule

  ADTT: Aberration of the Drug's Therapeutic Target

  MRAP: Metabolic Reprogramming via Altered Pathways

Drug Resistance Data Categorized by Drug

Approved Drug(s) 2 drug(s) in total

Oxaliplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Colorectal cancer [ICD-11: 2B91.1] [1]

• Metabolic Type: Lipid metabolism
• Resistant Disease: Colorectal cancer [ICD-11: 2B91.1]
• Resistant Drug: Oxaliplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HT-29 cells; Colon; Homo sapiens (Human); CVCL_0320
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: our findings revealed that oxaliplatin impressed a specific lipid profile signature and lipid transcriptional reprogramming in HT29 cells, which provides new insights into biomarker discovery and pathways for overcoming drug resistance and adverse reactions.

Valdecoxib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Rheumatoid arthritis [ICD-11: FA20.0] [2]

• Resistant Disease: Rheumatoid arthritis [ICD-11: FA20.0]
• Resistant Drug: Valdecoxib
• Molecule Alteration: Function; Inhibition
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Hela cells; Cervix uteri; Homo sapiens (Human); CVCL_0030
• In Vivo Model: Standard diet fed male C57BL/6J (B6) mouse model; HFD fed male C57BL/6J (B6) mouse model; Mus musculus
• Experiment for Molecule Alteration: Enzyme linked immunosorbent assay; Western blot analysis
• Mechanism Description: Valdecoxib improves lipid-induced skeletal muscle insulin resistance via simultaneous suppression of inflammation and endoplasmic reticulum stress.

Disease Class: Osteoarthritis [ICD-11: FB84.2] [2]

• Resistant Disease: Osteoarthritis [ICD-11: FB84.2]
• Resistant Drug: Valdecoxib
• Molecule Alteration: Function; Inhibition
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Hela cells; Cervix uteri; Homo sapiens (Human); CVCL_0030
• In Vivo Model: Standard diet fed male C57BL/6J (B6) mouse model; HFD fed male C57BL/6J (B6) mouse model; Mus musculus
• Experiment for Molecule Alteration: Enzyme linked immunosorbent assay; Western blot analysis
• Mechanism Description: Valdecoxib improves lipid-induced skeletal muscle insulin resistance via simultaneous suppression of inflammation and endoplasmic reticulum stress.

Disease Class: Dysmenorrhea [ICD-11: GA34.3] [2]

• Resistant Disease: Dysmenorrhea [ICD-11: GA34.3]
• Resistant Drug: Valdecoxib
• Molecule Alteration: Function; Inhibition
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Hela cells; Cervix uteri; Homo sapiens (Human); CVCL_0030
• In Vivo Model: Standard diet fed male C57BL/6J (B6) mouse model; HFD fed male C57BL/6J (B6) mouse model; Mus musculus
• Experiment for Molecule Alteration: Enzyme linked immunosorbent assay; Western blot analysis
• Mechanism Description: Valdecoxib improves lipid-induced skeletal muscle insulin resistance via simultaneous suppression of inflammation and endoplasmic reticulum stress.

Investigative Drug(s) 2 drug(s) in total

IMC-HA

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Acute myeloid leukemia [ICD-11: 2A60.0] [3]

• Sensitive Disease: Acute myeloid leukemia [ICD-11: 2A60.0]
• Sensitive Drug: IMC-HA
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: THP-1 cells; monocytic; Homo sapiens (Human); N.A.
• In Vitro Model: U937 cells; Blood; Homo sapiens (Human); CVCL_0007
• Experiment for Molecule Alteration: Western blot assay; Molecular docking assay
• Experiment for Drug Resistance: Cell viability assay; Apoptosis assay; Cell cycle assay; HDAC activity assay
• Mechanism Description: In this study, we designed and synthesized dual cyclooxygenase-2 (COX-2) and histone deacetylase (HDAC) inhibitors, IMC-HA and IMC-OPD, and applied them for the treatment of AML. IMC-HA comprised a COX-2 inhibitor skeleton of indomethacin (IMC) and an HDAC inhibitor moiety of the hydroxamic group and was found to exhibit potent antiproliferative activity against AML cells (THP-1 and U937) and low cytotoxicity toward normal cells. Molecular docking simulations suggested that IMC-HA had a high binding affinity for HDAC and COX-2, with binding energies of -6.8 and -9.0 kcal/mol, respectively. Mechanistic studies revealed that IMC-HA induced apoptosis and G0/G1 phase arrest in AML cells, which were characterized by alterations in the expression of apoptotic and cell cycle-related proteins. Further study demonstrated that IMC-HA also inhibited the MEK/ERK signaling pathway in AML cells. Overall, we believe that IMC-HA could serve as a potent COX-2/HDAC dual inhibitor and improve the treatment of AML.

IMC-OPD

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Acute myeloid leukemia [ICD-11: 2A60.0] [3]

• Sensitive Disease: Acute myeloid leukemia [ICD-11: 2A60.0]
• Sensitive Drug: IMC-OPD
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: THP-1 cells; monocytic; Homo sapiens (Human); N.A.
• In Vitro Model: U937 cells; Blood; Homo sapiens (Human); CVCL_0007
• Experiment for Molecule Alteration: Western blot assay; Molecular docking assay
• Experiment for Drug Resistance: Cell viability assay; Apoptosis assay; Cell cycle assay; HDAC activity assay
• Mechanism Description: In this study, we designed and synthesized dual cyclooxygenase-2 (COX-2) and histone deacetylase (HDAC) inhibitors, IMC-HA and IMC-OPD, and applied them for the treatment of AML. IMC-HA comprised a COX-2 inhibitor skeleton of indomethacin (IMC) and an HDAC inhibitor moiety of the hydroxamic group and was found to exhibit potent antiproliferative activity against AML cells (THP-1 and U937) and low cytotoxicity toward normal cells. Molecular docking simulations suggested that IMC-HA had a high binding affinity for HDAC and COX-2, with binding energies of -6.8 and -9.0 kcal/mol, respectively. Mechanistic studies revealed that IMC-HA induced apoptosis and G0/G1 phase arrest in AML cells, which were characterized by alterations in the expression of apoptotic and cell cycle-related proteins. Further study demonstrated that IMC-HA also inhibited the MEK/ERK signaling pathway in AML cells. Overall, we believe that IMC-HA could serve as a potent COX-2/HDAC dual inhibitor and improve the treatment of AML.

References

• Ref 1: Lipidomics and transcriptomics analyses of altered lipid species and pathways in oxaliplatin-treated colorectal cancer cells. J Pharm Biomed Anal. 2021 Jun 5;200:114077.
• Ref 2: Valdecoxib improves lipid-induced skeletal muscle insulin resistance via simultaneous suppression of inflammation and endoplasmic reticulum stress .Biochem Pharmacol. 2021 Jun;188:114557. doi: 10.1016/j.bcp.2021.114557. Epub 2021 Apr 18. 10.1016/j.bcp.2021.114557
• Ref 3: A potent dual inhibitor targeting COX-2 and HDAC of acute myeloid leukemia cells. Mol Divers. 2025 Jun;29(3):2433-2444.