SC-236
Explore a selection of our essential drug information below, or:
Identification
- Generic Name
- SC-236
- DrugBank Accession Number
- DB14059
- Background
SC-236 is a potent, selective, orally active inhibitor of cyclooxygenase-2 (COX-2) 12 that has been studied in cancer therapy 3, lower back pain 4, and inflammation 1, 2,11, 5.
- Type
- Small Molecule
- Groups
- Experimental, Investigational
- Structure
- Weight
- Average: 401.79
Monoisotopic: 401.02126 - Chemical Formula
- C16H11ClF3N3O2S
- Synonyms
- Not Available
- External IDs
- SC 236
- SC-236
- SC236
Pharmacology
- Indication
Not Available
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- Pharmacodynamics
Not Available
- Mechanism of action
This drug is a selective inhibitor of the COX-2 enzyme 2, 3. COX-2 is expressed in the brain, in the kidney, in bone, and likely in the female reproductive system 14. Its expression at other sites is increased during inflammation, experimentally, in response to mitogenic stimuli. Growth factors, phorbol esters, and interleukin (IL)-1 stimulate the expression of COX-2 in fibroblasts, while endotoxin serves the same function in monocytes/macrophages 14.
SC-236 works also directly through suppressing the nuclear translocation of RelA/p65, a transcription factor. SC-236 directly targets proteins that facilitate the nuclear translocation of NF-κB, an inflammatory signaling pathway 2, 8.
Target Actions Organism ACyclooxygenase 2 inhibitorCanis lupus familiaris AProstaglandin G/H synthase 2 inhibitorHumans ANuclear factor NF-kappa-B complex inhibitorHumans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
Long plasma half-life 6.
- Clearance
Not Available
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir SC-236 may decrease the excretion rate of Abacavir which could result in a higher serum level. Abciximab The risk or severity of bleeding and hemorrhage can be increased when SC-236 is combined with Abciximab. Acebutolol SC-236 may decrease the antihypertensive activities of Acebutolol. Aceclofenac The risk or severity of adverse effects can be increased when Aceclofenac is combined with SC-236. Acemetacin The risk or severity of adverse effects can be increased when Acemetacin is combined with SC-236. - Food Interactions
- Not Available
Categories
- Drug Categories
- Agents causing hyperkalemia
- Agents that produce hypertension
- Amides
- Analgesics
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Antirheumatic Agents
- Benzene Derivatives
- Cyclooxygenase Inhibitors
- Enzyme Inhibitors
- Nephrotoxic agents
- Peripheral Nervous System Agents
- Sensory System Agents
- Sulfonamides
- Sulfones
- Sulfur Compounds
- Classification
- Not classified
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 9HGW1H8S2M
- CAS number
- 170569-86-5
- InChI Key
- NSQNZEUFHPTJME-UHFFFAOYSA-N
- InChI
- InChI=1S/C16H11ClF3N3O2S/c17-11-3-1-10(2-4-11)14-9-15(16(18,19)20)22-23(14)12-5-7-13(8-6-12)26(21,24)25/h1-9H,(H2,21,24,25)
- IUPAC Name
- 4-[5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzene-1-sulfonamide
- SMILES
- NS(=O)(=O)C1=CC=C(C=C1)N1N=C(C=C1C1=CC=C(Cl)C=C1)C(F)(F)F
References
- General References
- Kim SJ, Jeong HJ, Moon PD, Myung NY, Kim MC, Kang TH, Lee KM, Park RK, So HS, Kim EC, An NH, Um JY, Kim HM, Hong SH: The COX-2 inhibitor SC-236 exerts anti-inflammatory effects by suppressing phosphorylation of ERK in a murine model. Life Sci. 2007 Aug 23;81(11):863-72. doi: 10.1016/j.lfs.2007.06.027. Epub 2007 Sep 5. [Article]
- Kim SJ, Jeong HJ, Choi IY, Lee KM, Park RK, Hong SH, Kim HM: Cyclooxygenase-2 inhibitor SC-236 [4-[5-(4-chlorophenyl)-3-(trifluoromethyl)-1-pyrazol-1-l] benzenesulfonamide] suppresses nuclear factor-kappaB activation and phosphorylation of p38 mitogen-activated protein kinase, extracellular signal-regulated kinase, and c-Jun N-terminal kinase in human mast cell line cells. J Pharmacol Exp Ther. 2005 Jul;314(1):27-34. doi: 10.1124/jpet.104.082792. Epub 2005 Mar 22. [Article]
- Wong BC, Jiang XH, Lin MC, Tu SP, Cui JT, Jiang SH, Wong WM, Yuen MF, Lam SK, Kung HF: Cyclooxygenase-2 inhibitor (SC-236) suppresses activator protein-1 through c-Jun NH2-terminal kinase. Gastroenterology. 2004 Jan;126(1):136-47. [Article]
- Deleo TA, Hashizume H, Rutkowski MD, Weinstein TN: Cyclooxygenase-2 inhibitor SC-236 attenuates mechanical allodynia following nerve root injury in rats. J Orthop Res. 2000 Nov;18(6):977-82. doi: 10.1002/jor.1100180618. [Article]
- Jiang XH, Lam SK, Lin MC, Jiang SH, Kung HF, Slosberg ED, Soh JW, Weinstein IB, Wong BC: Novel target for induction of apoptosis by cyclo-oxygenase-2 inhibitor SC-236 through a protein kinase C-beta(1)-dependent pathway. Oncogene. 2002 Sep 5;21(39):6113-22. doi: 10.1038/sj.onc.1205778. [Article]
- Penning TD, Talley JJ, Bertenshaw SR, Carter JS, Collins PW, Docter S, Graneto MJ, Lee LF, Malecha JW, Miyashiro JM, Rogers RS, Rogier DJ, Yu SS, AndersonGD, Burton EG, Cogburn JN, Gregory SA, Koboldt CM, Perkins WE, Seibert K, Veenhuizen AW, Zhang YY, Isakson PC: Synthesis and biological evaluation of the 1,5-diarylpyrazole class of cyclooxygenase-2 inhibitors: identification of 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benze nesulfonamide (SC-58635, celecoxib). J Med Chem. 1997 Apr 25;40(9):1347-65. [Article]
- Dai Y, Wang WH: Non-steroidal anti-inflammatory drugs in prevention of gastric cancer. World J Gastroenterol. 2006 May 14;12(18):2884-9. [Article]
- Wong BC, Jiang Xh, Fan XM, Lin MC, Jiang SH, Lam SK, Kung HF: Suppression of RelA/p65 nuclear translocation independent of IkappaB-alpha degradation by cyclooxygenase-2 inhibitor in gastric cancer. Oncogene. 2003 Feb 27;22(8):1189-97. doi: 10.1038/sj.onc.1206234. [Article]
- Randall E. Harris (2002). COX-2 Blockade in Cancer Prevention and Therapy. Humana Press.
- Luka Milas, K. K Ang, C. Nieder (2003). Modification of Radiation Response: Cytokines, Growth Factors, and Other Biological Targets (Medical Radiology). Springer.
- Comparative Protection against Liver Inflammation and Fibrosis by a Selective Cyclooxygenase-2 Inhibitor and a Nonredox-Type 5-Lipoxygenase Inhibitor [Link]
- SC-236 [Link]
- Enhancement of Tumor Response to -Radiation by an Inhibitor of Cyclooxygenase-2 Enzyme [Link]
- Overview of selective COX-2 inhibitors [Link]
- External Links
- ChemSpider
- 8041499
- BindingDB
- 50057527
- ChEMBL
- CHEMBL282093
- ZINC
- ZINC000000600558
- MSDS
- Download (72.3 KB)
Clinical Trials
- Clinical Trials
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Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source water solubility insoluble MSDS - Predicted Properties
Property Value Source Water Solubility 0.004 mg/mL ALOGPS logP 4.51 ALOGPS logP 4.1 Chemaxon logS -5 ALOGPS pKa (Strongest Acidic) 10.6 Chemaxon pKa (Strongest Basic) -0.44 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 77.98 Å2 Chemaxon Rotatable Bond Count 4 Chemaxon Refractivity 92 m3·mol-1 Chemaxon Polarizability 35.2 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0udi-0000900000-bc0b3ecc07476da16bfa Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0udi-0000900000-eff4dcc980556f22265c Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-001i-9000400000-14f0fb71bfe47a48abf1 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0udi-0001900000-8d1f734a33675cee47fb Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-001i-9000000000-0325ebaf0b61b7f5c12d Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0udi-0229000000-47b7059bc736b28e33ed Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Not Available
Targets
- Kind
- Protein
- Organism
- Canis lupus familiaris
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Not Available
- Specific Function
- enzyme binding
- Gene Name
- PTGS2
- Uniprot ID
- Q8SPQ9
- Uniprot Name
- Cyclooxygenase 2
- Molecular Weight
- 68974.625 Da
References
- Nonsteroidal Antiinflammatory Drugs and a Selective Cyclooxygenase 2 Inhibitor Uncouple Mitochondria in Intact Cells [Link]
- The COX-2 inhibitor SC-236 exerts anti-inflammatory effects by suppressing phosphorylation of ERK in a murine model [Link]
- A cyclooxygenase-2 (COX-2) inhibitor compared with dexamethasone in a survival study of rats with intracerebral 9L gliosarcomas [File]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Dual cyclooxygenase and peroxidase in the biosynthesis pathway of prostanoids, a class of C20 oxylipins mainly derived from arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate, AA, C20:4(n-6)), with a particular role in the inflammatory response (PubMed:11939906, PubMed:16373578, PubMed:19540099, PubMed:22942274, PubMed:26859324, PubMed:27226593, PubMed:7592599, PubMed:7947975, PubMed:9261177). The cyclooxygenase activity oxygenates AA to the hydroperoxy endoperoxide prostaglandin G2 (PGG2), and the peroxidase activity reduces PGG2 to the hydroxy endoperoxide prostaglandin H2 (PGH2), the precursor of all 2-series prostaglandins and thromboxanes (PubMed:16373578, PubMed:22942274, PubMed:26859324, PubMed:27226593, PubMed:7592599, PubMed:7947975, PubMed:9261177). This complex transformation is initiated by abstraction of hydrogen at carbon 13 (with S-stereochemistry), followed by insertion of molecular O2 to form the endoperoxide bridge between carbon 9 and 11 that defines prostaglandins. The insertion of a second molecule of O2 (bis-oxygenase activity) yields a hydroperoxy group in PGG2 that is then reduced to PGH2 by two electrons (PubMed:16373578, PubMed:22942274, PubMed:26859324, PubMed:27226593, PubMed:7592599, PubMed:7947975, PubMed:9261177). Similarly catalyzes successive cyclooxygenation and peroxidation of dihomo-gamma-linoleate (DGLA, C20:3(n-6)) and eicosapentaenoate (EPA, C20:5(n-3)) to corresponding PGH1 and PGH3, the precursors of 1- and 3-series prostaglandins (PubMed:11939906, PubMed:19540099). In an alternative pathway of prostanoid biosynthesis, converts 2-arachidonoyl lysophopholipids to prostanoid lysophopholipids, which are then hydrolyzed by intracellular phospholipases to release free prostanoids (PubMed:27642067). Metabolizes 2-arachidonoyl glycerol yielding the glyceryl ester of PGH2, a process that can contribute to pain response (PubMed:22942274). Generates lipid mediators from n-3 and n-6 polyunsaturated fatty acids (PUFAs) via a lipoxygenase-type mechanism. Oxygenates PUFAs to hydroperoxy compounds and then reduces them to corresponding alcohols (PubMed:11034610, PubMed:11192938, PubMed:9048568, PubMed:9261177). Plays a role in the generation of resolution phase interaction products (resolvins) during both sterile and infectious inflammation (PubMed:12391014). Metabolizes docosahexaenoate (DHA, C22:6(n-3)) to 17R-HDHA, a precursor of the D-series resolvins (RvDs) (PubMed:12391014). As a component of the biosynthetic pathway of E-series resolvins (RvEs), converts eicosapentaenoate (EPA, C20:5(n-3)) primarily to 18S-HEPE that is further metabolized by ALOX5 and LTA4H to generate 18S-RvE1 and 18S-RvE2 (PubMed:21206090). In vascular endothelial cells, converts docosapentaenoate (DPA, C22:5(n-3)) to 13R-HDPA, a precursor for 13-series resolvins (RvTs) shown to activate macrophage phagocytosis during bacterial infection (PubMed:26236990). In activated leukocytes, contributes to oxygenation of hydroxyeicosatetraenoates (HETE) to diHETES (5,15-diHETE and 5,11-diHETE) (PubMed:22068350, PubMed:26282205). Can also use linoleate (LA, (9Z,12Z)-octadecadienoate, C18:2(n-6)) as substrate and produce hydroxyoctadecadienoates (HODEs) in a regio- and stereospecific manner, being (9R)-HODE ((9R)-hydroxy-(10E,12Z)-octadecadienoate) and (13S)-HODE ((13S)-hydroxy-(9Z,11E)-octadecadienoate) its major products (By similarity). During neuroinflammation, plays a role in neuronal secretion of specialized preresolving mediators (SPMs) 15R-lipoxin A4 that regulates phagocytic microglia (By similarity)
- Specific Function
- enzyme binding
- Gene Name
- PTGS2
- Uniprot ID
- P35354
- Uniprot Name
- Prostaglandin G/H synthase 2
- Molecular Weight
- 68995.625 Da
References
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. In a non-canonical activation pathway, the MAP3K14-activated CHUK/IKKA homodimer phosphorylates NFKB2/p100 associated with RelB, inducing its proteolytic processing to NFKB2/p52 and the formation of NF-kappa-B RelB-p52 complexes. The NF-kappa-B heterodimeric RelB-p52 complex is a transcriptional activator. The NF-kappa-B p52-p52 homodimer is a transcriptional repressor. NFKB2 appears to have dual functions such as cytoplasmic retention of attached NF-kappa-B proteins by p100 and generation of p52 by a cotranslational processing. The proteasome-mediated process ensures the production of both p52 and p100 and preserves their independent function. p52 binds to the kappa-B consensus sequence 5'-GGRNNYYCC-3', located in the enhancer region of genes involved in immune response and acute phase reactions. p52 and p100 are respectively the minor and major form; the processing of p100 being relatively poor. Isoform p49 is a subunit of the NF-kappa-B protein complex, which stimulates the HIV enhancer in synergy with p65. In concert with RELB, regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-BMAL1 heterodimer
- Specific Function
- DNA-binding transcription activator activity, RNA polymerase II-specific
Components:
Name | UniProt ID |
---|---|
Nuclear factor NF-kappa-B p100 subunit | Q00653 |
Nuclear factor NF-kappa-B p105 subunit | P19838 |
Transcription factor p65 | Q04206 |
References
- Wong BC, Jiang Xh, Fan XM, Lin MC, Jiang SH, Lam SK, Kung HF: Suppression of RelA/p65 nuclear translocation independent of IkappaB-alpha degradation by cyclooxygenase-2 inhibitor in gastric cancer. Oncogene. 2003 Feb 27;22(8):1189-97. doi: 10.1038/sj.onc.1206234. [Article]
- Kim SJ, Jeong HJ, Choi IY, Lee KM, Park RK, Hong SH, Kim HM: Cyclooxygenase-2 inhibitor SC-236 [4-[5-(4-chlorophenyl)-3-(trifluoromethyl)-1-pyrazol-1-l] benzenesulfonamide] suppresses nuclear factor-kappaB activation and phosphorylation of p38 mitogen-activated protein kinase, extracellular signal-regulated kinase, and c-Jun N-terminal kinase in human mast cell line cells. J Pharmacol Exp Ther. 2005 Jul;314(1):27-34. doi: 10.1124/jpet.104.082792. Epub 2005 Mar 22. [Article]
- Cyclooxygenase-2 Inhibitor SC-236 [4-[5-(4-Chlorophenyl)-3-(trifluoromethyl)-1-pyrazol-1-l] Benzenesulfonamide] Suppresses Nuclear Factor-κB Activation and Phosphorylation of p38 Mitogen-Activated Protein Kinase, Extracellular Signal-Regulated Kinase, and c-Jun N-Terminal Kinase in Human Mast Cell Line Cells [Link]
Drug created at June 14, 2018 19:34 / Updated at August 26, 2024 19:22