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Details

Stereochemistry ABSOLUTE
Molecular Formula C21H28N4O5
Molecular Weight 416.4708
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ADERBASIB

SMILES

COC(=O)N1CC2(CC2)C[C@@H]([C@H]1C(=O)N3CCN(CC3)C4=CC=CC=C4)C(=O)NO

InChI

InChIKey=DJXMSZSZEIKLQZ-IRXDYDNUSA-N
InChI=1S/C21H28N4O5/c1-30-20(28)25-14-21(7-8-21)13-16(18(26)22-29)17(25)19(27)24-11-9-23(10-12-24)15-5-3-2-4-6-15/h2-6,16-17,29H,7-14H2,1H3,(H,22,26)/t16-,17-/m0/s1

HIDE SMILES / InChI

Molecular Formula C21H28N4O5
Molecular Weight 416.4708
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: The description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/18757423 | http://cancerres.aacrjournals.org/content/69/24_Supplement/5056 | https://goo.gl/5qWyaC

Aderbasib, also known as INCB007839, is an orally bioavailable low nanomolar hydroxamate-based inhibitor of the ADAM (A Disintegrin And Metalloprotease) family of multifunctional membrane-bound proteins with potential antineoplastic activity. Aderbasib represses the metalloproteinase "sheddase" activities of ADAM10 and ADAM17, which may result in the inhibition of tumor cell proliferation. In preclinical studies, Aderbasib with lapatinib prevented the growth of HER-2/neu–positive BT474-SC1 human breast cancer xenografts in vivo. Aderbasib was being developed by Incyte as a potential adjunctive treatment for metastatic breast cancer. Aderbasib in combination with trastuzumab increased the response rate in HER2 positive metastatic breast cancer patients with advanced disease, relative to historical controls (50% versus 15–35%). INC7839 also improved progression-free survival in a subset of the patients expressing the p95 fragment of HER2. Aderbasib development was halted in 2011 after positive findings from Phase II trials were contradicted by further research. Aderbasib is currently being tested in combination with rituximab for diffuse large B cell non-Hodgkin lymphoma.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
Synergistic inhibition with a dual epidermal growth factor receptor/HER-2/neu tyrosine kinase inhibitor and a disintegrin and metalloprotease inhibitor.
2008 Sep 1
Patents

Sample Use Guides

Three doses of INCB7839 were studied (100 mg, 200 mg, 300 mg BID) with 6 patients/cohort and an expansion arm at the 300mg BID dose
Route of Administration: Oral
The MCF-7 cells were grown in high glucose DMEM and MCF/18 cells were maintained in a 50:50 mix of Ham’s medium and high glucose DMEM supplemented with L-glutamine. Both cell lines were supplemented with 10% fetal bovine serum and maintained in 5% CO2 at 37C. G418 was added to the MCF/18 cell medium to support continued transfection. Cells were plated in 24-well plates at 20,000 per well and incubated overnight to allow attachment. Cells were treated with various concentrations of Aderbasib (0.25–40 mkmol/L) and/or GW2974 (0.025–1 Amol/L). As a control, cells were treated with corresponding concentrations of DMSO, the solvent for both agents. The cells were incubated for an additional 3 d, and the cell number was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Each single dose and combination was done in triplicate in each assay.
Substance Class Chemical
Created
by admin
on Fri Dec 15 15:32:37 GMT 2023
Edited
by admin
on Fri Dec 15 15:32:37 GMT 2023
Record UNII
V9YL6NEJ3G
Record Status Validated (UNII)
Record Version
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Name Type Language
ADERBASIB
INN   USAN   WHO-DD  
INN   USAN  
Official Name English
INCB-007839
Code English
INCB007839
Code English
aderbasib [INN]
Common Name English
Aderbasib [WHO-DD]
Common Name English
5-AZASPIRO(2.5)OCTANE-5-CARBOXYLIC ACID, 7-((HYDROXYAMINO)CARBONYL)-6-((4-PHENYL-1-PIPERAZINYL)CARBONYL)-, METHYL ESTER, (6S,7S)-
Common Name English
Methyl (6S,7S)-7-[(hydroxyamino)carbonyl]-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2.5]octane-5-carboxylate
Systematic Name English
ADERBASIB [USAN]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C783
Created by admin on Fri Dec 15 15:32:37 GMT 2023 , Edited by admin on Fri Dec 15 15:32:37 GMT 2023
Code System Code Type Description
INN
9008
Created by admin on Fri Dec 15 15:32:37 GMT 2023 , Edited by admin on Fri Dec 15 15:32:37 GMT 2023
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FDA UNII
V9YL6NEJ3G
Created by admin on Fri Dec 15 15:32:37 GMT 2023 , Edited by admin on Fri Dec 15 15:32:37 GMT 2023
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NCI_THESAURUS
C76115
Created by admin on Fri Dec 15 15:32:37 GMT 2023 , Edited by admin on Fri Dec 15 15:32:37 GMT 2023
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SMS_ID
100000176281
Created by admin on Fri Dec 15 15:32:37 GMT 2023 , Edited by admin on Fri Dec 15 15:32:37 GMT 2023
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CAS
791828-58-5
Created by admin on Fri Dec 15 15:32:37 GMT 2023 , Edited by admin on Fri Dec 15 15:32:37 GMT 2023
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ChEMBL
CHEMBL2103790
Created by admin on Fri Dec 15 15:32:37 GMT 2023 , Edited by admin on Fri Dec 15 15:32:37 GMT 2023
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PUBCHEM
16070111
Created by admin on Fri Dec 15 15:32:37 GMT 2023 , Edited by admin on Fri Dec 15 15:32:37 GMT 2023
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WIKIPEDIA
Aderbasib
Created by admin on Fri Dec 15 15:32:37 GMT 2023 , Edited by admin on Fri Dec 15 15:32:37 GMT 2023
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USAN
SS-18
Created by admin on Fri Dec 15 15:32:37 GMT 2023 , Edited by admin on Fri Dec 15 15:32:37 GMT 2023
PRIMARY
EPA CompTox
DTXSID701000327
Created by admin on Fri Dec 15 15:32:37 GMT 2023 , Edited by admin on Fri Dec 15 15:32:37 GMT 2023
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Related Record Type Details
ACTIVE MOIETY