This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

Name
SC-236
Accession Number
DB14059
Type
Small Molecule
Groups
Experimental, Investigational
Description

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].

Structure
Thumb
Synonyms
Not Available
External IDs
SC 236 / SC-236 / SC236
Categories
UNII
Not Available
CAS number
170569-86-5
Weight
Average: 401.79
Monoisotopic: 401.02126
Chemical Formula
C16H11ClF3N3O2S
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

Pharmacology

Indication
Not Available
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].

TargetActionsOrganism
ACyclooxygenase 2
inhibitor
Canis lupus familiaris
ANuclear factor NF-kappa-B complex
inhibitor
Human
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
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of bleeding and hemorrhage can be increased when SC-236 is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of bleeding and hemorrhage can be increased when SC-236 is combined with (S)-Warfarin.
4-hydroxycoumarinThe risk or severity of bleeding and hemorrhage can be increased when SC-236 is combined with 4-hydroxycoumarin.
AbacavirSC-236 may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbciximabThe risk or severity of bleeding and hemorrhage can be increased when SC-236 is combined with Abciximab.
AcarboseSC-236 may decrease the excretion rate of Acarbose which could result in a higher serum level.
AcebutololSC-236 may decrease the antihypertensive activities of Acebutolol.
AceclofenacThe risk or severity of adverse effects can be increased when Aceclofenac is combined with SC-236.
AcemetacinThe risk or severity of adverse effects can be increased when Acemetacin is combined with SC-236.
AcenocoumarolThe risk or severity of bleeding and hemorrhage can be increased when SC-236 is combined with Acenocoumarol.
Food Interactions
Not Available

References

General References
  1. 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. [PubMed:17822719]
  2. 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. [PubMed:15784648]
  3. 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. [PubMed:14699495]
  4. 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. [PubMed:11192259]
  5. 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. [PubMed:12203123]
  6. 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. [PubMed:9135032]
  7. Dai Y, Wang WH: Non-steroidal anti-inflammatory drugs in prevention of gastric cancer. World J Gastroenterol. 2006 May 14;12(18):2884-9. [PubMed:16718813]
  8. 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. [PubMed:12606945]
  9. Randall E. Harris (2002). COX-2 Blockade in Cancer Prevention and Therapy. Humana Press.
  10. Luka Milas, K. K Ang, C. Nieder (2003). Modification of Radiation Response: Cytokines, Growth Factors, and Other Biological Targets (Medical Radiology). Springer.
  11. Comparative Protection against Liver Inflammation and Fibrosis by a Selective Cyclooxygenase-2 Inhibitor and a Nonredox-Type 5-Lipoxygenase Inhibitor [Link]
  12. SC-236 [Link]
  13. Enhancement of Tumor Response to -Radiation by an Inhibitor of Cyclooxygenase-2 Enzyme [Link]
  14. Overview of selective COX-2 inhibitors [Link]
External Links
ChemSpider
8041499
BindingDB
50057527
ChEMBL
CHEMBL282093
MSDS
Download (72.3 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityinsoluble MSDS
Predicted Properties
PropertyValueSource
Water Solubility0.004 mg/mLALOGPS
logP4.51ALOGPS
logP4.1ChemAxon
logS-5ALOGPS
pKa (Strongest Acidic)10.6ChemAxon
pKa (Strongest Basic)-0.44ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area77.98 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity92 m3·mol-1ChemAxon
Polarizability35.2 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Classification
Not classified

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
  1. Nonsteroidal Antiinflammatory Drugs and a Selective Cyclooxygenase 2 Inhibitor Uncouple Mitochondria in Intact Cells [Link]
  2. The COX-2 inhibitor SC-236 exerts anti-inflammatory effects by suppressing phosphorylation of ERK in a murine model [Link]
  3. A cyclooxygenase-2 (COX-2) inhibitor compared with dexamethasone in a survival study of rats with intracerebral 9L gliosarcomas [File]
Kind
Protein group
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Transcriptional activator activity, rna polymerase ii core promoter proximal region sequence-specific binding
Specific 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...

Components:
References
  1. 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. [PubMed:12606945]
  2. 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. [PubMed:15784648]
  3. 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 on June 14, 2018 13:34 / Updated on November 02, 2018 07:49