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
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
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/28613012Curator'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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/28613012
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.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
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Target ID: CHEMBL3706 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28613012 |
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Target ID: CHEMBL5028 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28613012 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Sources: https://goo.gl/zTCgxW |
Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/18757423
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.
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C783
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CHEMBL2103790
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Aderbasib
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DTXSID701000327
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ACTIVE MOIETY