SELISISTAT

Investigational

Details

Stereochemistry	RACEMIC
Molecular Formula	C13H13ClN2O
Molecular Weight	248.708
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC(=O)C1CCCC2=C1NC3=C2C=C(Cl)C=C3

InChI

InChIKey=FUZYTVDVLBBXDL-UHFFFAOYSA-N

InChI=1S/C13H13ClN2O/c14-7-4-5-11-10(6-7)8-2-1-3-9(13(15)17)12(8)16-11/h4-6,9,16H,1-3H2,(H2,15,17)

HIDE SMILES / InChI

Molecular Formula	C13H13ClN2O
Molecular Weight	248.708
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

Description
Sources: http://www.businesswire.com/news/home/20100107005499/en/Elixir-Announces-Sirtuin-Inhibitor-Clinical-Trial | https://www.ncbi.nlm.nih.gov/pubmed/16354677

Selisistat (EX 527) was discovered by Elixir scientists as a selective human SIRT1 inhibitor and exhibits >200-fold selectivity against SIRT2 and SIRT3. Human SIRT1 is an enzyme that deacetylates the p53 tumor suppressor protein and has been suggested to modulate p53-dependent functions including DNA damage-induced cell death. It was shown that drug was highly safe in toxicology studies. Selisistat passed Phase II clinical trials to treat Huntington’s disease, but that study was discontinued.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
NAD-dependent protein deacetylase sirtuin-1 3 Target ID: Q96EB6 Gene ID: 23411.0 Gene Symbol: SIRT1 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/16354677	Inhibitor 8504		38.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Huntington's disease 28 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25223836	Primary		Phase II 1147	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
4.3 μM EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25223836	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		SELISISTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
26.6 μM EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25223836	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:		SELISISTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
19.3 μM × h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25223836	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		SELISISTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
319 μM × h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25223836	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:		SELISISTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
2.43 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25223836	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		SELISISTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
6.12 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25223836	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:		SELISISTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Doses

Dose	Population	Adverse events
600 mg single, oral Highest studied dose Dose: 600 mg Route: oral Route: single Dose: 600 mg Sources: https://pubmed.ncbi.nlm.nih.gov/25223836	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M Food Status: FASTED Sources: https://pubmed.ncbi.nlm.nih.gov/25223836	Sources: https://pubmed.ncbi.nlm.nih.gov/25223836
300 mg 1 times / day multiple, oral Studied dose Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/25223836	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M Food Status: FASTED Sources: https://pubmed.ncbi.nlm.nih.gov/25223836	Sources: https://pubmed.ncbi.nlm.nih.gov/25223836

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY116098	https://www.001chemical.com/chem/49843-98-3
001 Chemical	DY574243	https://www.001chemical.com/chem/848193-68-0
3B Scientific (Wuhan) Corp	3B3-072762	http://www.3bsc.com/index/pro_info.php?id=113875
AA Blocks	AA00DA7U	https://www.aablocks.com/goods/Goods/detail?id=AA00DA7U
Aaron Chemicals	AR00DAZM	http://www.aaronchem.com/49843-98-3
abcr GmbH	AB349034	http://www.abcr.com/shop/en/AB349034
AbMole Bioscience	1708	http://www.abmole.com/product.asp?id=1708
AbMole Bioscience	M1708	http://www.abmole.com/products/ex-527.html
Acadechem	ACDS-049129	http://www.acadechemical.com/product/123828
Active Biopharma	ABP000688	http://www.activebiopharma.com/848193-68-0
AHH Chemical co.,ltd	MT-45436	http://www.ahhchemical.com/product/MT-45436.html
AK Scientific, Inc. (AKSCI)	X7534	http://www.aksci.com/item_detail.php?cat=X7534
Alfa Chemistry	AP49843983-A	https://reagents.alfa-chemistry.com/product/ex-527-cas-49843-98-3-12023.html
Alfa Chemistry	AP49843983-B	https://reagents.alfa-chemistry.com/product/sirt1-inhibitor-iii-cas-49843-98-3-12024.html
Allbio Pharm Co., Ltd	AF09178	http://www.allbiopharm.com/product/n/AF09178
Ambeed	A142021	https://www.ambeed.com/products/49843-98-3.html
Ambinter	Amb1052696	http://www.ambinter.com/reference/1052696
Ark Pharm	AK162085	http://www.arkpharminc.com/products/49843-98-3.html
Ark Pharma Scientific Limited	H-015879	http://www.arkpharmtech.com/product/20934.html
Aurora Fine Chemicals LLC	A00.669.790	http://online.aurorafinechemicals.com/info?ID=A00.669.790
Aurora Fine Chemicals LLC	K00.404.066	http://online.aurorafinechemicals.com/info?ID=K00.404.066
Aurum Pharmatech LLC	S-7754	http://www.Aurumpharmatech.com/Product/ProductDetails/S_7754
AvaChem Scientific	6326	https://www.avachem.com/productSearch.asp?6326
Axon MedChem	1956	https://www.axonmedchem.com/product/1956
BioChemPartner	BCP02889	http://www.biochempartner.com/49843-98-3-BCP02889
BioCrick	BCC2223	http://www.biocrick.com/EX-527-SEN0014196-BCC2223.html
BLD Pharm	BD108686	http://www.bldpharm.com/products/49843-98-3.html
BOC Sciences	49843-98-3	https://www.bocsci.com/ex-527-cas-49843-98-3-item-84-216313.html
BOC Sciences	848193-68-0	https://www.bocsci.com/ex-527-s-enantiomer-cas-848193-68-0-item-84-463649.html
BOC Sciences	848193-69-1	https://www.bocsci.com/ex-527-r-enantiomer-cas-848193-69-1-item-84-463650.html
Boerchem	BC623031	http://www.boerchem.com/?product_43084.html
Calbiochem	566322	http://www.emdbiosciences.com/product/566322
Chem Scene	CS-0960	http://www.chemscene.com/49843-98-3.html
ChemMol	51503352	http://www.chemmol.com/chemmol/51503352.html
ChemMol	97900911	http://www.chemmol.com/chemmol/97900911.html
ChemMol	99090035	http://www.chemmol.com/chemmol/99090035.html
ChemShuttle	104904	http://www.chemshuttle.com/catalogsearch/result/?q=49843-98-3&cat=
Chemspace	CSSB00015189192	https://chem-space.com/CSSB00015189192
Combi-Blocks	QJ-5511	http://www.combi-blocks.com/cgi-bin/find.cgi?QJ-5511
CSNpharm	CSN10146	https://www.csnpharm.com/products/ex-527.html
DC Chemicals	DC7127	http://www.dcchemicals.com/product_show-EX_527_Selisistat_.html
Debye Scientific	DB-082965	http://www.debyesci.com/cas_49843-98-3.html
EMD Millipore	566322	http://www.emdbiosciences.com/product/566322
eNovation Chemicals	D501966	https://www.enovationchem.com/ProductDetails.asp?ProductID=D501966
eNovation Chemicals	Y0991765	https://www.enovationchem.com/ProductDetails.asp?ProductID=Y0991765
Excenen	EX-A1064	http://www.excenen.com/searchresultlist.php?id=49843-98-3
Finetech	FT-0698480	http://www.finetechnology-ind.com/prod/detail/pub/49843-98-3.html
iChemical	EBD45623	http://www.ichemical.com/chemicals/cas-49843-98-3
Lab Network	LN01326573	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01326573
Matrix Scientific	125496	https://www.matrixscientific.com/125496.html
mcule	MCULE-2491423827	https://mcule.com/MCULE-2491423827/
MedChem Express	HY-15452	https://www.medchemexpress.com/EX-527.html
Molcore	MC116098	https://www.molcore.com/product/49843-98-3
Molcore	MC574243	https://www.molcore.com/product/848193-68-0
MolPort	MolPort-003-761-515	https://www.molport.com/shop/molecule-link/MolPort-003-761-515
MuseChem	I003752	https://www.musechem.com/product/I003752.html
Selleck Chemicals	S1541	http://www.selleckchem.com/products/EX-527.html
Sigma-Aldrich	E7034_SIGMA	https://www.sigmaaldrich.com/catalog/product/sigma/e7034?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sinfoo Biotech	S033472	http://www.sinfoobiotech.com/product/1036870
Smolecule	S542949	http://www.smolecule.com/products/s542949
Sun-shine Chemical	6-chloro-2	http://www.sun-shinechem.com/49843-98-3.html
Synblock Inc	SB16664	http://www.synblock.com/product/49843-98-3.html
Synchem UG and Co KG	68613	http://www.synchem.de/chemical_6-Chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide.html
TCI (Tokyo Chemical Industry)	C2739	http://www.tcichemicals.com/eshop/en/us/commodity/C2739/index.html
THE BioTek	bt-282533	https://www.thebiotek.com/product/inhibitors/bt-282533
TimTec	SBB014468	http://www.echemstore.com/sbb014468-6-chloro-1-2-3-4-9-pentahydro-4ah-carbazolecarboxamide.html
TimTec	ST082785	http://www.echemstore.com/st082785-6-chloro-1-2-3-4-9-pentahydro-4ah-carbazolecarboxamide.html
Tocris	2780	https://www.tocris.com/products/ex-527_2780
Vitas-M Laboratory	STK522511	http://www.request.vitasmlab.biz/index.php?option=com_search_stk&Itemid=22&stk=STK522511&?utm_source=pubchem&utm_medium=p_search_link&utm_campaign=pubchem_search&utm_content=pubchem_slink

PubMed

Title	Date	PubMed
Resveratrol via sirtuin-1 downregulates RE1-silencing transcription factor (REST) expression preventing PCB-95-induced neuronal cell death.	2015-11-01	26307266
BET Inhibition Upregulates SIRT1 and Alleviates Inflammatory Responses.	2015-09-21	26212199
Non-specific SIRT inhibition as a mechanism for the cytotoxicity of ginkgolic acids and urushiols.	2014-09-02	24998427
SIRT1 inhibition restores apoptotic sensitivity in p53-mutated human keratinocytes.	2014-06-15	24726431
Des-acyl ghrelin protects microvascular endothelial cells from oxidative stress-induced apoptosis through sirtuin 1 signaling pathway.	2014-04	24486147
Sesamin ameliorates doxorubicin-induced cardiotoxicity: involvement of Sirt1 and Mn-SOD pathway.	2014-01-13	24211423
Resveratrol differentially regulates NAMPT and SIRT1 in Hepatocarcinoma cells and primary human hepatocytes.	2014	24603648
Resveratrol induces a mitochondrial complex I-dependent increase in NADH oxidation responsible for sirtuin activation in liver cells.	2013-12-20	24178296
Resveratrol suppresses the STAT3 signaling pathway and inhibits proliferation of high glucose-exposed HepG2 cells partly through SIRT1.	2013-12	24064760
Age-associated changes in gene expression and developmental competence of bovine oocytes, and a possible countermeasure against age-associated events.	2013-07	23712640
Resveratrol protects HUVECs from oxidized-LDL induced oxidative damage by autophagy upregulation via the AMPK/SIRT1 pathway.	2013-06	23358928
SIRT1 inhibits NADPH oxidase activation and protects endothelial function in the rat aorta: implications for vascular aging.	2013-05-01	23422569
Resveratrol improves cardiomyopathy in dystrophin-deficient mice through SIRT1 protein-mediated modulation of p300 protein.	2013-02-22	23297412
Resveratrol ameliorates ionizing irradiation-induced long-term hematopoietic stem cell injury in mice.	2013-01	23124026
Regulation of FOXOs and p53 by SIRT1 modulators under oxidative stress.	2013	24040102
Activation of SIRT1 protects pancreatic β-cells against palmitate-induced dysfunction.	2012-11	22968147
Sirt1 overexpression protects murine osteoblasts against TNF-α-induced injury in vitro by suppressing the NF-κB signaling pathway.	2012-05	22447223
Resveratrol reverses monocrotaline-induced pulmonary vascular and cardiac dysfunction: a potential role for atrogin-1 in smooth muscle.	2011-08-25	22146233
SIRT1 activation by resveratrol ameliorates cisplatin-induced renal injury through deacetylation of p53.	2011-08	21593185
Fructose induces gluconeogenesis and lipogenesis through a SIRT1-dependent mechanism.	2011-03	21212096
Resveratrol potentiates glucose-stimulated insulin secretion in INS-1E beta-cells and human islets through a SIRT1-dependent mechanism.	2011-02-25	21163946
Resveratrol prevents RANKL-induced osteoclast differentiation of murine osteoclast progenitor RAW 264.7 cells through inhibition of ROS production.	2010-10-22	20851107
SIRT1 modulates expression of matrix metalloproteinases in human dermal fibroblasts.	2010-10	20426787
Acetylation of tau inhibits its degradation and contributes to tauopathy.	2010-09-23	20869593
Agrp neurons mediate Sirt1's action on the melanocortin system and energy balance: roles for Sirt1 in neuronal firing and synaptic plasticity.	2010-09-01	20810901
Early apoptotic vascular signaling is determined by Sirt1 through nuclear shuttling, forkhead trafficking, bad, and mitochondrial caspase activation.	2010-05	20370652
SIRT inhibitors induce cell death and p53 acetylation through targeting both SIRT1 and SIRT2.	2010-04	20371709
N(epsilon)-thioacetyl-lysine-containing tri-, tetra-, and pentapeptides as SIRT1 and SIRT2 inhibitors.	2009-04-09	19296597
Inhibition of SIRT1 catalytic activity increases p53 acetylation but does not alter cell survival following DNA damage.	2006-01	16354677
Discovery of indoles as potent and selective inhibitors of the deacetylase SIRT1.	2005-12-15	16335928
The Sir2 family of protein deacetylases.	2004	15189148

Sample Use Guides

In Vivo Use Guide

100 mg, immediate release tablets, once daily administration. Subjects in the Fasted group will take study drug after an overnight fast (since at least midnight).

Route of Administration: Oral

In Vitro Use Guide

It was used EX-527 (selisistat) to examine the role of SIRT1 in p53 acetylation and cell survival after DNA damage. Treatment with EX-527 dramatically increased acetylation at lysine 382 of p53 after different types of DNA damage in primary human mammary epithelial cells and several cell lines. Significantly, inhibition of SIRT1 catalytic activity by EX-527 had no effect on cell growth, viability, or p53-controlled gene expression in cells treated with etoposide. Acetyl-p53 was also increased by the histone deacetylase (HDAC) class I/II inhibitor trichostatin A (TSA). EX-527 and TSA acted synergistically to increase acetyl-p53 levels, confirming that p53 acetylation is regulated by both SIRT1 and HDACs. While TSA alone reduced cell survival after DNA damage, the combination of EX-527 and TSA had no further effect on cell viability and growth. The deacetylation assay was performed with approximately 30 ng of GST-SIRT1 in the presence of EX-527 (48 pM to 100 μM). To determine the effects of deacetylase inhibitors on p53 acetylation levels, cells were treated with 6.25 to 400 nM TSA and/or 1 μM EX-527.

Substance Class	Chemical Created by `admin` on `Wed Apr 02 08:45:36 GMT 2025` Edited by `admin` on `Wed Apr 02 08:45:36 GMT 2025`
Record UNII	L19ECD5014
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

selisistat [INN]

Preferred Name

English

SELISISTAT

Official Name

English

Selisistat [WHO-DD]

Common Name

English

RAC-6-CHLORO-2,3,4,9-TETRAHYDRO-1H-CARBAZOLE-1-CARBOXAMIDE

Common Name

English

Classification Tree Code System Code

EU-Orphan Drug

EU/3/09/681