U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C22H22FN5O3
Molecular Weight 423.4402
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of SPEBRUTINIB

SMILES

COCCOC1=CC=C(NC2=NC=C(F)C(NC3=CC(NC(=O)C=C)=CC=C3)=N2)C=C1

InChI

InChIKey=KXBDTLQSDKGAEB-UHFFFAOYSA-N
InChI=1S/C22H22FN5O3/c1-3-20(29)25-16-5-4-6-17(13-16)26-21-19(23)14-24-22(28-21)27-15-7-9-18(10-8-15)31-12-11-30-2/h3-10,13-14H,1,11-12H2,2H3,(H,25,29)(H2,24,26,27,28)

HIDE SMILES / InChI

Description

Spebrutinib (CC-292, AVL-292) is a selective inhibitor of BTK that was under clinical development for the treatment of rheumatoid arthritis (phase II) and B-cell Lymphoma (phase I). The drug was discovered by Avila Therapeutics, but then acquired by Celgene. Spebrutinib covalently binds to Cys 481 in BTK, blocking the ATP-binding pocket of the enzyme. The drug is no longer in Celgene's pipeline and its development is supposed to be terminated.

Originator

Approval Year

Unknown
149124
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8504
 5.9 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Palliative
Phase II
1147
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1851 ng/mL
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/27151992
750 mg single, oral
dose: 750 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
SPEBRUTINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
7972 ng × h/mL
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/27151992
750 mg single, oral
dose: 750 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
SPEBRUTINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
2.8 h
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/28543084
200 mg 1 times / day multiple, oral
dose: 200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
SPEBRUTINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Sourcing

Sourcing

Vendor/AggregatorIDURL
1PlusChem LLC
1P003AN8
https://www.1pchem.com/search?query=1P003AN8
AA Blocks
AA003A3S
http://aablocks.com/goods/Goods/detail?id=AA003A3S
AbovChem LLC
HY-18012A
http://www.abovchem.com/pc/en/product_list.aspx?wd=HY-18012A
AChemBlock
H-8741
http://www.achemblock.com/catalogsearch/result/?q=H-8741
AK Scientific
2235AH
https://aksci.com/item_detail.php?cat=2235AH
AK Scientific
SYN5695
https://aksci.com/item_detail.php?cat=SYN5695
Ambeed
A537377
http://www.ambeed.com/search/Search.html?keyword=A537377
Angene
AGN-PC-0WAKN6
http://www.angenechemical.com/productshow/AGN-PC-0WAKN6.html
AOBIOUS INC
AOB87153
http://aobious.com/aobious/search?search_query=AOB87153
ApexBio Technology
A3206
https://www.apexbt.com/catalogsearch/result/?q=A3206
AstaTech
42169
http://astatechinc.com/CPSResult.php?CRNO=42169
Axon MedChem
2226
https://www.axonmedchem.com/product/2226
BLD Pharm
BD328411
http://www.bldpharm.com/search/Search.html?keyword=BD328411
BLD Pharm
BD630181
http://www.bldpharm.com/search/Search.html?keyword=BD630181
Capot Chemical
2692
https://www.capotchem.com/search.do?q=2692
Cayman Chemical
17993
http://www.caymanchem.com/app/template/Product.vm/catalog/17993
Chem Scene
CS-1482
http://www.chemscene.com/goproductList/searchProductList?productObj=CS-1482
ChemShuttle
125000
https://www.chemshuttle.com/catalogsearch/result/?q=125000
Combi-Blocks
QJ-1395
http://www.combi-blocks.com/cgi-bin/find.cgi?QJ-1395
Debye Scientific
DA-35316
https://www.debyesci.com/index.php?id=product&ext[cno]=DA-35316
eMolecules
252348624
https://orderbb.emolecules.com/search/#?query=252348624
eMolecules
46339059
https://orderbb.emolecules.com/search/#?query=46339059
eMolecules
50284139
https://orderbb.emolecules.com/search/#?query=50284139
eNovation Chemicals
D572704
https://www.enovationchem.com/Products.asp?SEARCHTEXT=D572704&searchbtn.x=0&searchbtn.y=0
Excenen
EX-A255
http://www.excenen.com/searchresultlist.php?id=EX-A255
KeyOrganics
AS-16998
http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-16998
Lab Seeker
SC-94180
http://www.labseeker.com/search.php?keywords=SC-94180&category=0
LabSeeker
SC-94180
http://www.labseeker.com/search.php?keywords=SC-94180&category=0
Matrix Scientific
148415
http://www.matrixscientific.com/148415.html
mcule
MCULE-4788692981
https://mcule.com/MCULE-4788692981/
mcule
MCULE-5639095348
https://mcule.com/MCULE-5639095348/
MedChem Express
HY-18012
https://www.medchemexpress.com/search.html?q=HY-18012&ft=&fa=&fp=
Molnova
M10735
https://www.molnova.com/en/serch-list.html?keywords=M10735
Molnova
M11478
https://www.molnova.com/en/serch-list.html?keywords=M11478
MolPort
MolPort-028-720-820
https://www.molport.com/shop/molecule-link/MolPort-028-720-820
MuseChem
441
https://www.musechem.com/product/441.html
MuseChem
I000746
https://www.musechem.com/product/I000746.html
Ryan Scientific
101-94185
https://ryansci.com/products?q=101-94185&list_q=&search_type=exact
Ryan Scientific
RN486
https://ryansci.com/products?q=RN486&list_q=&search_type=exact
Selleck Chemicals
S7173
http://www.selleckchem.com/search.html?searchDTO.searchParam=S7173
ShangHai Biochempartner
BCP000890
http://www.biochempartner.com/search_BCP000890
ShangHai Biochempartner
BCP07702
http://www.biochempartner.com/search_BCP07702
ShangHai Biochempartner
BCP16838
http://www.biochempartner.com/search_BCP16838
Synovel
SN-0090
http://www.synovellab.com/?s=SN-0090&submit=Search
TargetMol
T2603
https://www.targetmol.com/search?keyword=T2603
Toronto Research Chemicals
A794715
https://www.trc-canada.com/product-detail/?CatNum=A794715
Toronto Research Chemicals
T795133
https://www.trc-canada.com/product-detail/?CatNum=T795133
PubMed

PubMed

TitleDatePubMed
Phase I study of single-agent CC-292, a highly selective Bruton's tyrosine kinase inhibitor, in relapsed/refractory chronic lymphocytic leukemia.
2016-07
A novel Bruton's tyrosine kinase inhibitor CC-292 in combination with the proteasome inhibitor carfilzomib impacts the bone microenvironment in a multiple myeloma model with resultant antimyeloma activity.
2014-09
Bruton's tyrosine kinase (BTK) inhibitors in clinical trials.
2014-03
B cell receptor pathway in chronic lymphocytic leukemia: specific role of CC-292.
2014
Inhibition of Btk with CC-292 provides early pharmacodynamic assessment of activity in mice and humans.
2013-08
Tyrosine kinase inhibitors as potential drugs for B-cell lymphoid malignancies and autoimmune disorders.
2012-07
Patents

Patents

20100029610
2
20100249092
2
20120077832
2
20130065899
2
20130072469
2

Sample Use Guides

In Vivo Use Guide
Patients should take oral spebrutinib in a dose of 375 mg daily (250 mg in the AM and 125 mg in the PM for 28 days).
Route of Administration: Oral
In Vitro Use Guide
Cells from the Ramos lymphoma cell line, which expresses an intact BCR signaling pathway, were treated with increasing concentrations of spebrutinib for 1 hour and lysed, and the percent occupancy of BTK was determined with ELISA. The concentration of spebrutinib required for 50% occupancy was 5.9 nM.
Name Type Language
SPEBRUTINIB
INN   USAN   WHO-DD  
USAN   INN  
Official Name English
spebrutinib [INN]
Preferred Name English
3-(5-FLUORO-2-(4-(2-METHOXYETHOXY)PHENYLAMINO)PYRIMIDIN-4-YLAMINO)PHENYL)ACRYLAMIDE
Systematic Name English
CC-292
Code English
AVL-292
Code English
SPEBRUTINIB [USAN]
Common Name English
Spebrutinib [WHO-DD]
Common Name English
N-(3-((5-FLUORO-2-((4-(2-METHOXYETHOXY)PHENYL)AMINO)PYRIMIDIN-4-YL)AMINO)PHENYL)ACRYLAMIDE
Systematic Name English
BTK INHIBITOR CC-292
Common Name English
2-PROPENAMIDE, N-(3-((5-FLUORO-2-((4-(2-METHOXYETHOXY)PHENYL)AMINO)-4-PYRIMIDINYL)AMINO)PHENYL)-
Systematic Name English
Classification Tree Code System Code
NCI_THESAURUS C124801
Created by admin on Mon Mar 31 19:12:02 GMT 2025 , Edited by admin on Mon Mar 31 19:12:02 GMT 2025
NCI_THESAURUS C129825
Created by admin on Mon Mar 31 19:12:02 GMT 2025 , Edited by admin on Mon Mar 31 19:12:02 GMT 2025
FDA ORPHAN DRUG 408313
Created by admin on Mon Mar 31 19:12:02 GMT 2025 , Edited by admin on Mon Mar 31 19:12:02 GMT 2025
Code System Code Type Description
DRUG BANK
DB11764
Created by admin on Mon Mar 31 19:12:02 GMT 2025 , Edited by admin on Mon Mar 31 19:12:02 GMT 2025
PRIMARY
SMS_ID
100000169951
Created by admin on Mon Mar 31 19:12:02 GMT 2025 , Edited by admin on Mon Mar 31 19:12:02 GMT 2025
PRIMARY
NCI_THESAURUS
C97037
Created by admin on Mon Mar 31 19:12:02 GMT 2025 , Edited by admin on Mon Mar 31 19:12:02 GMT 2025
PRIMARY
EVMPD
SUB183689
Created by admin on Mon Mar 31 19:12:02 GMT 2025 , Edited by admin on Mon Mar 31 19:12:02 GMT 2025
PRIMARY
ChEMBL
CHEMBL3301625
Created by admin on Mon Mar 31 19:12:02 GMT 2025 , Edited by admin on Mon Mar 31 19:12:02 GMT 2025
PRIMARY
EPA CompTox
DTXSID101026012
Created by admin on Mon Mar 31 19:12:02 GMT 2025 , Edited by admin on Mon Mar 31 19:12:02 GMT 2025
PRIMARY
INN
10004
Created by admin on Mon Mar 31 19:12:02 GMT 2025 , Edited by admin on Mon Mar 31 19:12:02 GMT 2025
PRIMARY
CAS
1202757-89-8
Created by admin on Mon Mar 31 19:12:02 GMT 2025 , Edited by admin on Mon Mar 31 19:12:02 GMT 2025
PRIMARY
USAN
AB-94
Created by admin on Mon Mar 31 19:12:02 GMT 2025 , Edited by admin on Mon Mar 31 19:12:02 GMT 2025
PRIMARY
FDA UNII
DRU6NG543J
Created by admin on Mon Mar 31 19:12:02 GMT 2025 , Edited by admin on Mon Mar 31 19:12:02 GMT 2025
PRIMARY
PUBCHEM
59174488
Created by admin on Mon Mar 31 19:12:02 GMT 2025 , Edited by admin on Mon Mar 31 19:12:02 GMT 2025
PRIMARY
ACTIVE MOIETY
Structure of SPEBRUTINIB
SALT/SOLVATE (PARENT)
Structure of SPEBRUTINIB BESYLATE
NIH
NCATS
PRIVACY NOTICE
ACCESSIBILITY
DISCLAIMER
HHS VULNERABILITY DISCLOSURE
For language access assistance, contact the NCATS Public Information Officer
National Center for Advancing Translational Sciences (NCATS),
6701 Democracy Boulevard, Bethesda MD 20892-4874 • 301-594-8966