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Drug

D0115 | Sulindac

Molecular Formula C20H17FO3S
Molecular Weight 356.4
Structure
State solid
Clearance * Renal cl=68.12 +/- 27.56 mL/min [NORMAL (19-41 yrs)]
Route of elimination Sulindac is excreted in rat milk; concentrations in milk were 10 to 20% of those levels in plasma. It is not known if sulindac is excreted in human milk. Approximately 50% of the administered dose of sulindac is excreted in the urine with the conjugated sulfone metabolite accounting for the major portion. Hepatic metabolism is an important elimination pathway.
Protein binding At 1 mcg/ml concentrations, approximately 93% sulindac and 98% of its sulfide metabolite are bound to human serum albumin.
Half life The mean half-life of sulindac is 7.8 hours while the mean half-life of the sulfide metabolite is 16.4 hours.
Absorption Approximately 90% absorbed in humans following oral administration.
Trade names Clinoril
Description nonsteroidal anti-inflammatory drug (NSAID) of the arylalkanoic acid class

M

M01AB02 Sulindac


[M01AB] Acetic acid derivatives and related substances


[M01A] ANTIINFLAMMATORY AND ANTIRHEUMATIC PRODUCTS, NON-STEROIDS


[M01] ANTIINFLAMMATORY AND ANTIRHEUMATIC PRODUCTS


[M] Musculoskeletal system

Toxicity Dose Time Species Model Method Action Positive criterion Reference
TRANSMEMBRANE POTENTIAL NR 24hr rat hepatocytes tetramethylrhodamine ethyl ester (TMRE) Negative AC50 (μM) 40
OPENING OF PERMEABILITY TRANSITION PORE (PTP) increase 45
MEMBRANE POTENTIAL > 200 µM 30 mins mouse liver mitochondria Rh123 fluorescence (excitation 485 nm, emission 535 nm) are recorded using a fluorescence multi-well plate reader (mCICCP (20 µM) treatments was considered as the 100% baseline for ΔΨm loss) decrease EC20 36
RESPIRATION > 400 µM 60 mins mouse liver mitochondria Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Rotenone (2µM) was used as 100% baseline for complex I inhibition. decrease EC20 36
RESPIRATION 35.6 µM 60 mins mouse liver mitochondria Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Oligomycin A (1µM) was used as 100% baseline for complex II inhibition. decrease EC20 36
STATE 2 RESPIRATION > 100 rat isolated rat liver mitochondria State 2 respiration ( 96-well plate format using a phosphorescent oxygen-sensitive probe MitoXpress) inhibit UC50 (nmol/mg mitochondrial protein) 40
STATE 3 RESPIRATION 100 nmol/mg mitochondrial protein rat isolated rat liver mitochondria State 3 respiration ( 96-well plate format using a phosphorescent oxygen-sensitive probe MitoXpress) Negative IC50 (nmol/mg mitochondrial protein) 40
LIPID METABOLISM NR 24hr rat hepatocytes LipidTox, for neutral lipid accumulation, to evaluate lipid content. Negative AC50 (μM) 40
GLUTATHIONE METABOLISM 896 24hr rat hepatocytes glutathion depletion: cells were incubated with 50 μM monochlorobimane with 6 μg/ml Hoechst 33342 AC50 (μM) 40
SWELLING > 200 µM 30 mins mouse liver mitochondria swelling assay: Absorbance at 545 nm using a fluorescence multi-well plate reader (CaCl2 (50 µM) was considered as the 100% baseline for the swelling ) increase EC20 36
OXIDATIVE STRESS increase 45
ROS PRODUCTION NR rat hepatocytes use CM-H2DCFDA to monitor reactive oxygen species Negative AC50 (μM) 40
CYTOCHROME C RELEASE NR 24hr rat hepatocytes cytochrome c release (anti-cytochrome c antibody ) Negative AC50 (μM) 40
ER STRESS-INDUCED NR 24hr rat hepatocytes DNA damage 153 induction (GADD153 antibodies) for ER-stress induced apoptosis Negative AC50 (μM) 40

Target Dose Time Species Model Method Action Positive criterion Reference
NADH:ubiquinone reductase > 400 µM 60 mins mouse liver mitochondria Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Rotenone (2µM) was used as 100% baseline for complex I inhibition. inhibit EC20 36
Succinate dehydrogenase 35.6 µM 60 mins mouse liver mitochondria Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Oligomycin A (1µM) was used as 100% baseline for complex II inhibition. inhibit EC20 36
Reactive oxygen species increase 45
Cytochrome c > 200 µM 30 mins mouse liver mitochondria Cytochrome c release was evaluated using ELISA kit ( 20 µg/ml Alamethicin was used as 100% baseline) release EC20 36

Pictogram Signal Statements Precautionary Statement Codes
Danger

Aggregated GHS information provided by 77 companies from 5 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.


Reported as not meeting GHS hazard criteria by 1 of 77 companies. For more detailed information, please visit ECHA C&L website


Of the 4 notification(s) provided by 76 of 77 companies with hazard statement code(s):


H301 (98.68%): Toxic if swallowed [Danger Acute toxicity, oral]


H317 (52.63%): May cause an allergic skin reaction [Warning Sensitization, Skin]


H319 (46.05%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]


H334 (52.63%): May cause allergy or asthma symptoms or breathing difficulties if inhaled [Danger Sensitization, respiratory]


H360 (46.05%): May damage fertility or the unborn child [Danger Reproductive toxicity]


H361 (52.63%): Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]


H373 (46.05%): Causes damage to organs through prolonged or repeated exposure [Warning Specific target organ toxicity, repeated exposure]


Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.


 P201, P202, P260, P261, P264, P270, P272, P280, P281, P285, P301+P310, P302+P352, P304+P341, P305+P351+P338, P308+P313, P314, P321, P330, P333+P313, P337+P313, P342+P311, P363, P405, and P501; (The corresponding statement to each P-code can be found at the GHS Classification page.)

  • Ankylosing spondylitis

  • Arthritis

  • Back pain

  • Bedridden

  • Bursitis

  • Gout

  • Gouty arthritis

  • Mixed connective tissue disease

  • Osteoarthritis

  • Rheumatic disorder

  • Rheumatoid arthritis

  • Rotator cuff syndrome

  • Systemic lupus erythematosus

  • Tenosynovitis

  • Gastrointestinal pain (0.1)

    • (Z)-(1)-5-Fluoro-2-methyl-1-((4-(methylsulphinyl)phenyl)methylene)-1H-indene-3-acetic acid (Z)-2-(5-Fluoro-2-methyl-1-(4-(methylsulfinyl)-benzylidene)-1H-inden-3-yl)acetic acid (Z)-2-(5-Fluoro-2-methyl-1-(4-(methylsulfinyl)benzylidene)-1H-inden-3-yl)acetic acid
    (Z)-2-[5-Fluoro-2-methyl-1-[4-(methylsulfinyl)benzylidene]-1H-inden-3-yl]acetic Acid (Z)-5-Fluoro-2-methyl-1-((p-(methylsulfinyl)phenyl)methylene)-1H-indene-3-acetic acid (Z)-5-Fluoro-2-methyl-1-[(p-methylsulfinyl)benzylidene]-1H-indene-3-acetic Acid
    (Z)-5-Fluoro-2-methyl-1-[[4-(methyl-sulfinyl)phenyl]methylene]-1H-indene-3-acetic acid (Z)-5-fluoro-2-methyl-1-[[4-(methylsulfinyl)-phenyl]methylene]-1H-indene-3-acetic acid 1H-Indene-3-acetic acid, 5-fluoro-2-methyl-1-((4-(methylsulfinyl)phenyl)methylene)-, (Z)-
    1H-Indene-3-acetic acid, 5-fluoro-2-methyl-1-[[4-(methylsulfinyl)phenyl]methylene]-, (1Z)- 2-(5-fluoro-2-methyl-1-{[4-(methylsulfinyl)phenyl]methylene}inden-3-yl)acetic acid 2-[(1Z)-5-fluoro-1-[(4-methanesulfinylphenyl)methylidene]-2-methyl-1H-inden-3-yl]acetic acid
    2-[(3Z)-6-fluoro-2-methyl-3-[(4-methylsulfinylphenyl)methylene]inden-1-yl]acetic acid 2-[(3Z)-6-fluoro-2-methyl-3-[(4-methylsulfinylphenyl)methylidene]inden-1-yl]acetic acid 32004-68-5
    38194-50-2 5-Fluoro-2-methyl-1-((4-(methylsulphinyl)phenyl)methylene)-1H-indene-3-acetic acid 9222-EP2275420A1
    9222-EP2277565A2 9222-EP2277566A2 9222-EP2277567A1
    9222-EP2277568A2 9222-EP2277569A2 9222-EP2277570A2
    9222-EP2280008A2 9222-EP2281815A1 9222-EP2284166A1
    9222-EP2292280A1 9222-EP2295055A2 9222-EP2295409A1
    9222-EP2298764A1 9222-EP2298765A1 9222-EP2301933A1
    9222-EP2305640A2 9222-EP2305652A2 9222-EP2308872A1
    9222-EP2311453A1 9222-EP2311827A1 9222-EP2314585A1
    9222-EP2314590A1 9222-EP2316829A1 AB00052105-07
    AB00052105_08 AB00052105_09 AB00513800
    AB2000418 AKOS015895412 Aflodac
    Algocetil Arthrobid Arthrocine
    Artribid BDBM50012899 BDBM50103504
    BP-30208 BPBio1_000315 BRD-A13946108-001-04-9
    BRD-A13946108-001-08-0 BRN 2951842 BSPBio_000285
    BSPBio_002890 C01531 C20H17FO3S
    CAS-38194-50-2 CCG-39264 CCRIS 3305
    CHEBI:9352 CHEBI:93811 CHEMBL15770
    CPD000326718 CS-0569 Citireuma
    Clinoril Clinoril (TN) Clinoril;Aflodac;Sulreuma
    Clisundac D00120 DB00605
    DSSTox_CID_3624 DSSTox_GSID_23624 DSSTox_RID_77117
    DTXSID4023624 EINECS 250-893-8 EINECS 253-819-2
    EINECS 256-402-3 EU-0101070 GTPL5425
    HMS1921C11 HMS2092K15 HMS2095O07
    HMS2231N24 HMS3259K06 HMS3263E22
    HMS3414N11 HMS3649P19 HMS3678N09
    HMS3712O07 HMS501O03 HY-B0008
    IDI1_000601 Imbaral J-008554
    J-012337 KS-5153 Klinoril
    LP01070 LS-81610 Lopac-S-8139
    Lopac0_001070 MK 231 MK-231
    MLKXDPUZXIRXEP-MFOYZWKCSA-N MLS001056554 Mobilin
    Moblilin NC00540 NCGC00015970-01
    NCGC00015970-02 NCGC00015970-03 NCGC00015970-04
    NCGC00015970-05 NCGC00015970-06 NCGC00015970-07
    NCGC00015970-08 NCGC00015970-11 NCGC00025268-01
    NCGC00025268-02 NCGC00025268-03 NCGC00094349-01
    NCGC00094349-02 NCGC00255143-01 NCGC00261755-01
    NSC-757344 NSC757344 Pharmakon1600-01500556
    Prestwick3_000073 Q963093 RT-000169
    Reumofil S 8139 SAM002554933
    SBB058181 SBI-0051040.P004 SCHEMBL4202
    SCHEMBL4203 SMR000326718 SPECTRUM1500556
    SR-01000075237 SR-01000075237-13 SR-01000075237-2
    SR-01000075237-3 SR-01000075237-5 SR-01000075237-7
    ST24026687 ST51015123 SW219748-1
    Spectrum5_001024 Sudac Sulindac (Clinoril)
    Sulindac (JP17/USP/INN) Sulindac [USAN:BAN:INN:JAN] Sulindac [USAN:USP:INN:BAN:JAN]
    Sulindac sulfoxide Sulindac, >=98.0% Sulindac, European Pharmacopoeia (EP) Reference Standard
    Sulindac, United States Pharmacopeia (USP) Reference Standard Sulindac, meets USP testing specifications Sulindaco
    Sulindaco [INN-Spanish] Sulindacum Sulindacum [INN-Latin]
    Sulindac|(1Z)-5-Fluoro-2-methyl-1-[[4-(methylsulfinyl)phenyl]methylene]-1H-indene-3-acetic acid Sulinol Sulreuma
    Tocris-1707 Tox21_110270 Tox21_110270_1
    Tox21_301418 Tox21_501070 U0099
    W-5115 cMAP_000021 cis-5-Fluoro-2-methyl-1-((4-(methylsulfinyl)phenyl)methylene)-1H-indene-3-acetic acid
    cis-5-Fluoro-2-methyl-1-((p-methylsulfinyl)benzylidene)indene-3-acetic acid cis-5-Fluoro-2-methyl-1-((p-methylsulfinyl)benzylidenyl)indene-3-acetic acid cis-Sulindac
    s2007 sulindac {(1Z)-5-fluoro-2-methyl-1-[4-(methylsulfinyl)benzylidene]-1H-inden-3-yl}acetic acid
    {(1z)-5-fluoro-2-methyl-1-[4-(methylsulfinyl)benzylidene]-1h-indene-3-yl}acetic acid

    DrugBank Name Sulindac
    DrugBank DB00605
    CAS Number 32004-68-5, 38194-50-2, 49627-22-7, 9000-14-0
    PubChem Compound 1548887
    KEGG Compound ID C01531
    KEGG Drug D00120
    PubChem.Substance 46506570
    ChEBI 9352
    PharmGKB PA451565
    ChemSpider 1265915
    BindingDB 50012899.0
    TTD DAP000569
    Wikipedia Sulindac
    DPD 2126

    1. Dykens et al. (2007)