EXISULIND

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C20H17FO4S
Molecular Weight	372.41
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1=C(CC(O)=O)C2=CC(F)=CC=C2\C1=C/C3=CC=C(C=C3)S(C)(=O)=O

InChI

InChIKey=MVGSNCBCUWPVDA-MFOYZWKCSA-N

InChI=1S/C20H17FO4S/c1-12-17(9-13-3-6-15(7-4-13)26(2,24)25)16-8-5-14(21)10-19(16)18(12)11-20(22)23/h3-10H,11H2,1-2H3,(H,22,23)/b17-9-

HIDE SMILES / InChI

Molecular Formula	C20H17FO4S
Molecular Weight	372.41
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	1
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/11358813 | https://www.ncbi.nlm.nih.gov/pubmed/11249724 | https://www.ncbi.nlm.nih.gov/pubmed/15230629

Exisulind (tentative trade name Aptosyn) is an antineoplastic agent, which was originally developed by Cell Pathways. This drug is an inhibitor of phosphodiesterase (PDE) isozymes: PDE5 and PDE4. Inhibition of PDE5 appears to be pharmacologically relevant, which leads to increase cGMP and activate protein kinase G at doses that induce apoptosis, whereas cyclic AMP levels were not changed. Exisulind has been in phase III clinical trials for the treatment of Non-Small Cell Lung Cancer and for the treatment of polyps in patients who have familial adenomatous polyposis (Colorectal Cancer and Small Intestine Cancer). In addition, this drug was in phase II/III for the treatment of Prostate Cancer, however, there studies have been discontinued.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Phosphodiesterase 5A 31 Target ID: CHEMBL1827 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11358813	Inhibitor 8504		112.0 µM [IC50]
Phosphodiesterase 4 54 Target ID: CHEMBL2093863 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11358813	Inhibitor 8504		116.0 µM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Colorectal cancer 102 Sources: https://clinicaltrials.gov/ct2/show/NCT00026468	Primary	Phase III 665	Unknown Approved Use Unknown
Small intestine cancer 2 Sources: https://clinicaltrials.gov/ct2/show/NCT00026468	Primary	Phase III 665	Unknown Approved Use Unknown
Non-small cell lung cancer 211 Sources: https://clinicaltrials.gov/ct2/show/NCT00085826	Primary	Phase III 665	Unknown Approved Use Unknown
Prostate cancer 186 Sources: https://clinicaltrials.gov/ct2/show/NCT00078910	Primary	Phase II 1147	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
18.2 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10656435	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	EXISULIND plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
9.85 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10656435	400 mg 2 times / day single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	EXISULIND plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
48.1 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10656435	400 mg 2 times / day multiple, oral dose: 400 mg route of administration: Oral experiment type: MULTIPLE co-administered:	EXISULIND plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
127 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10656435	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	EXISULIND plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
48.7 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10656435	400 mg 2 times / day single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	EXISULIND plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
174 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10656435	400 mg 2 times / day multiple, oral dose: 400 mg route of administration: Oral experiment type: MULTIPLE co-administered:	EXISULIND plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
6.03 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10656435	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	EXISULIND plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
4.88 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10656435	400 mg 2 times / day single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	EXISULIND plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
10.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10656435	400 mg 2 times / day multiple, oral dose: 400 mg route of administration: Oral experiment type: MULTIPLE co-administered:	EXISULIND plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252	inhibitor 2438	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYPs 29 CYP2E1 1060 CYP19A1 429 CYP1A2 2153 NTCP 39 CYP2C19 2057 OATPs 1 CYP2A6 879 MRP2 499	CYPs 33 UGT1A1 479 UGT1A3 470 UGT1A9 423 UGT2B15 236 UGT2B7 456 UGT2B17 237 UGT1A4 399 UGT1A6 343 UGT1A7 249 UGT1A8 323 UGT1A10 331 UGT2B4 278	CYP1A1 151 UGT1A1 78 GSTP1 1 CYP1A2 832 CYP1B1 71

Drug as perpetrator

Target	Modality	Activity
CYP3A4 2633	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645841#sid=170466321	inconclusive [IC50 13.8029 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=170466321	inconclusive [IC50 34.6713 uM]
CYP2A6 911	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/625246#sid=160698611	no [IC50 >10 uM]
CYP2E1 1146	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/625250#sid=160698611	no [IC50 >10 uM]
CYP19A1 430	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/743139#sid=144207073	no
CYP2C19 2141	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/899#sid=11111778	no
CYP2D6 2546	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/891#sid=11111778	no
CYPs 35	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/11772293/	no
CYP1A2 2333	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/410#sid=11111778	yes [IC50 12.6 uM]
CYP1A1 272	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/17985343/	yes
CYP1A2 2333	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/17985343/	yes
CYP1B1 93	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/17985343/	yes
GSTP1 1	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/17985343/	yes
MRP2 625	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/20430841/	yes
NTCP 40	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/20430841/	yes
OATPs 1	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/20430841/	yes
UGT1A1 303	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/17985343/	yes

Drug as victim

Target	Modality	Activity
UGT1A10 331	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15843492/	likely
UGT1A4 399	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15843492/	likely
UGT1A6 343	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15843492/	likely
UGT1A7 249	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15843492/	likely
UGT2B4 278	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15843492/	likely
CYPs 33	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11772293/	no
UGT2B15 236	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15843492/	no
UGT2B17 237	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15843492/	no
UGT1A3 470	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15843492/	yes [Km 15 uM]
UGT2B7 456	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15843492/	yes [Km 34.1 uM]
UGT1A9 423	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15843492/	yes [Km 44.6 uM]
UGT1A1 479	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15843492/	yes [Km 5.2 uM]
UGT1A8 323	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15843492/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/588834#sid=50107023

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P00E9KK	https://www.1pchem.com/search?query=1P00E9KK
1PlusChem LLC	1P00ECHB	https://www.1pchem.com/search?query=1P00ECHB
Alfa Chemistry	189139	http://www.alfa-chemistry.com/search.aspx?q=189139
Alfa Chemistry	ACM59973807	http://www.alfa-chemistry.com/search.aspx?q=ACM59973807
Angene	AGN-PC-0SU6WN	http://www.angenechemical.com/productshow/AGN-PC-0SU6WN.html
eMolecules	1934876	https://orderbb.emolecules.com/search/#?query=1934876
eMolecules	26751332	https://orderbb.emolecules.com/search/#?query=26751332
eMolecules	300088841	https://orderbb.emolecules.com/search/#?query=300088841
eNovation Chemicals	D759265	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D759265&searchbtn.x=0&searchbtn.y=0
Matrix Scientific	121209	http://www.matrixscientific.com/121209.html
MolPort	MolPort-003-850-357	https://www.molport.com/shop/molecule-link/MolPort-003-850-357
MuseChem	R002174	https://www.musechem.com/product/R002174.html
Toronto Research Chemicals	S699225	https://www.trc-canada.com/product-detail/?CatNum=S699225
Toronto Research Chemicals	S699323	https://www.trc-canada.com/product-detail/?CatNum=S699323

PubMed

Title	Date	PubMed
Structural analysis of sulindac as an inhibitor of aldose reductase and AKR1B10.	2015-06-05	25532697
Sulindac metabolites induce proteosomal and lysosomal degradation of the epidermal growth factor receptor.	2010-04	20332299
15-Hydroxyprostaglandin dehydrogenase (15-PGDH) is up-regulated by flurbiprofen and other non-steroidal anti-inflammatory drugs in human colon cancer HT29 cells.	2009-07-15	19501039
Phase I/II study of vinorelbine and exisulind as first-line treatment of advanced non-small cell lung cancer in patients at least 70 years old: a wisconsin oncology network study.	2008-09	18758305
Activation of protein kinase G Increases the expression of p21CIP1, p27KIP1, and histidine triad protein 1 through Sp1.	2008-07-01	18593937
The proapoptotic effects of sulindac, sulindac sulfone and indomethacin are mediated by nucleolar translocation of the RelA(p65) subunit of NF-kappaB.	2008-04-17	18059344
Sulindac and its metabolites induce carcinogen metabolizing enzymes in human colon cancer cells.	2008-03-01	17985343
A comparison of the effectiveness of selected non-steroidal anti-inflammatory drugs and their derivatives against cancer cells in vitro.	2008-02	17447067
Malignant transformation of normal enterocytes following downregulation of Bak expression.	2008	18349538
Exisulind in combination with celecoxib modulates epidermal growth factor receptor, cyclooxygenase-2, and cyclin D1 against prostate carcinogenesis: in vivo evidence.	2007-10-01	17908994
Nonsteroidal anti-inflammatory drugs induce colorectal cancer cell apoptosis by suppressing 14-3-3epsilon.	2007-04-01	17409426
Gene expression profiling in R-flurbiprofen-treated prostate cancer: R-Flurbiprofen regulates prostate stem cell antigen through activation of AKT kinase.	2006-11-15	16949054
Sulindac sulfide and exisulind inhibit expression of the estrogen and progesterone receptors in human breast cancer cells.	2006-06-01	16740773
Exisulind and guanylyl cyclase C induce distinct antineoplastic signaling mechanisms in human colon cancer cells.	2006-05	16731751
Sporadic adenomatous polyp regression with exisulind is effective but toxic: a randomised, double blind, placebo controlled, dose-response study.	2006-03	16150858
Induction of spermidine/spermine N1-acetyltransferase (SSAT) by aspirin in Caco-2 colon cancer cells.	2006-02-15	16262603
Activation of protein kinase G up-regulates expression of 15-lipoxygenase-1 in human colon cancer cells.	2005-09-15	16166323
Glucuronidation of nonsteroidal anti-inflammatory drugs: identifying the enzymes responsible in human liver microsomes.	2005-07	15843492
The nonsteroidal anti-inflammatory drug Exisulind selectively induces apoptosis via JNK in secondary acute myeloid leukemia after myelodysplastic syndrome.	2005-06	15970671
A phase I/II dose-escalation study of exisulind and docetaxel in patients with hormone-refractory prostate cancer.	2005-05	15839914
Nobiletin, a citrus flavonoid, down-regulates matrix metalloproteinase-7 (matrilysin) expression in HT-29 human colorectal cancer cells.	2005-02	15725655
Sulindac enhances adenoviral vector expressing mda-7/IL-24-mediated apoptosis in human lung cancer.	2005-02	15713900
Regression of mouse prostatic intraepithelial neoplasia by nonsteroidal anti-inflammatory drugs in the transgenic adenocarcinoma mouse prostate model.	2004-11-15	15570007
Inhibition of extracellular-signal regulated kinases 1/2 is required for apoptosis of human colon cancer cells in vitro by sulindac metabolites.	2004-11-15	15548677
Glutathione-S-transferase P1-1 protects aberrant crypt foci from apoptosis induced by deoxycholic acid.	2004-08	15300575
Effect of nonsteroidal anti-inflammatory drugs on beta-catenin protein levels and catenin-related transcription in human colorectal cancer cells.	2004-07-05	15188006
Cyclooxygenase-independent induction of apoptosis by sulindac sulfone is mediated by polyamines in colon cancer.	2003-11-28	14506281
Exisulind and related compounds inhibit expression and function of the androgen receptor in human prostate cancer cells.	2003-10-15	14581372
Sulindac metabolites induce caspase- and proteasome-dependent degradation of beta-catenin protein in human colon cancer cells.	2003-09	14555707
Pro-apoptotic actions of exisulind and CP461 in SW480 colon tumor cells involve beta-catenin and cyclin D1 down-regulation.	2002-11-01	12392815
PPARgamma-mediated antineoplastic effect of NSAID sulindac on human oral squamous carcinoma cells.	2002-04-20	11948457
Exisulind in combination with docetaxel inhibits growth and metastasis of human lung cancer and prolongs survival in athymic nude rats with orthotopic lung tumors.	2002-03	11895925
GATA-6 transcriptional regulation of 15-lipoxygenase-1 during NSAID-induced apoptosis in colorectal cancer cells.	2002-02-15	11861401
Cyclic GMP-dependent protein kinase activation and induction by exisulind and CP461 in colon tumor cells.	2001-11	11602670
Sulindac sulfide-induced apoptosis involves death receptor 5 and the caspase 8-dependent pathway in human colon and prostate cancer cells.	2001-09-15	11559570
Safety and efficacy of exisulind for treatment of recurrent prostate cancer after radical prostatectomy.	2001-09	11490238
Sulindac-associated choledocholithiasis.	2001-07	11467685
Rat colorectal tumours treated with a range of non-steroidal anti-inflammatory drugs show altered cyclooxygenase-2 and cyclooxygenase-1 splice variant mRNA expression levels.	2001-06	11375891
Protein kinase G activates the JNK1 pathway via phosphorylation of MEKK1.	2001-05-11	11278263
Sulindac sulfone inhibits K-ras-dependent cyclooxygenase-2 expression in human colon cancer cells.	2000-12-01	11118042
Non-steroidal anti-inflammatory drugs with different cyclooxygenase inhibitory profiles that prevent aberrant crypt foci formation but vary in acute gastrotoxicity in a rat model.	2000-12	11197048
Cyclic GMP mediates apoptosis induced by sulindac derivatives via activation of c-Jun NH2-terminal kinase 1.	2000-10	11051267
Exisulind induction of apoptosis involves guanosine 3',5'-cyclic monophosphate phosphodiesterase inhibition, protein kinase G activation, and attenuated beta-catenin.	2000-07-01	10910034
Inhibition of rat colon tumors by sulindac and sulindac sulfone is independent of K-ras (codon 12) mutation.	2000-02	10666051
Chemopreventive efficacy of sulindac sulfone against colon cancer depends on time of administration during carcinogenic process.	1999-07-15	10416599

Patents

Sample Use Guides

In Vivo Use Guide

patients with androgen independent prostate carcinoma: receive weekly docetaxel for 4 weeks, followed by 2 weeks of rest; repeated up to a maximum of 6 cycles. Exisulind 250 mg was given orally twice a day starting on day 8 of the study and taken continuously.

Route of Administration: Oral

In Vitro Use Guide

The effects of arsenic trioxide (ATO) in combination with sulindac (SUL), sulindac sulfide (SS) or sulindac sulfone (SF) on human (Jurkat, HL-60, K562 and HPB-ALL) and mouse (EL-4) leukemic cell lines were investigated. The combination of ATO (1 μM) with SS or SF at concentrations over 50 μM induced considerable cytotoxicity in all cell lines. Normal human lymphocytes exposed for 48 h to the combinations showed smaller decrease in viability. The mitochondrial membrane potential measurements (JC-1 probe) indicated an active involvement of mitochondria in the process. The results did not indicate involvement of an inhibitory effect of the combinations on NF-κB activity in Jurkat, HL-60 and K562 cells.

Substance Class	Chemical Created by `admin` on `Wed Apr 02 09:59:23 GMT 2025` Edited by `admin` on `Wed Apr 02 09:59:23 GMT 2025`
Record UNII	K619IIG2R9
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

SULINDAC RELATED COMPOUND B

Preferred Name

English

EXISULIND

Official Name

English

FGN-1

Code

English

SULINDAC IMPURITY B [EP IMPURITY]

Common Name

English

1H-Indene-3-acetic acid, 5-fluoro-2-methyl-1-[[4-(methylsulfonyl)phenyl]methylene]-, (1Z)-

Systematic Name

English

SULINDAC RELATED COMPOUND B [USP IMPURITY]

Common Name

English

SULINDAC SULFONE

Common Name

English

APTOSYN

Brand Name

English

SULINDAC RELATED COMPOUND B [USP-RS]

Common Name

English

EXISULIND [USAN]

Common Name

English

Exisulind [WHO-DD]

Common Name

English

EXISULIND [MI]

Common Name

English

5-Fluoro-2-methyl-1-[[4-(methylsulfonyl)phenyl]methylene]-1H-indene-3-acetic acid

Systematic Name

English

PREVATEC

Brand Name

English

EXISULIND [MART.]

Common Name

English

SULINDAC SULPHONE

Common Name

English

exisulind [INN]

Common Name

English

Classification Tree Code System Code

EU-Orphan Drug

EU/3/14/1387