Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C33H36N6O3S |
| Molecular Weight | 596.742 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CN1CCN(C)C(=O)[C@H]1C2=CC=C(NC3=NC(=CN(C)C3=O)C4=C(C)C(NC(=O)C5=CC6=C(CCCC6)S5)=CC=C4)C=C2
InChI
InChIKey=CDOOFZZILLRUQH-GDLZYMKVSA-N
InChI=1S/C33H36N6O3S/c1-20-24(9-7-10-25(20)36-31(40)28-18-22-8-5-6-11-27(22)43-28)26-19-39(4)33(42)30(35-26)34-23-14-12-21(13-15-23)29-32(41)38(3)17-16-37(29)2/h7,9-10,12-15,18-19,29H,5-6,8,11,16-17H2,1-4H3,(H,34,35)(H,36,40)/t29-/m1/s1
| Molecular Formula | C33H36N6O3S |
| Molecular Weight | 596.742 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
DescriptionCurator's Comment: Description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/21742900 | https://www.ncbi.nlm.nih.gov/pubmed/21521773 | https://www.ncbi.nlm.nih.gov/pubmed/23958373 | https://www.ncbi.nlm.nih.gov/pubmed/25845827
Curator's Comment: Description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/21742900 | https://www.ncbi.nlm.nih.gov/pubmed/21521773 | https://www.ncbi.nlm.nih.gov/pubmed/23958373 | https://www.ncbi.nlm.nih.gov/pubmed/25845827
(R)-N-(3-(6-(4-(1,4-dimethyl-3-oxopiperazin-2-yl)phenylamino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide (GDC-0834) is a potent and selective inhibitor of Bruton's tyrosine kinase (BTK). The compound demonstrates effective activity against BCR- and CD40-dependent B-cell proliferation and activation, and potently inhibits immune complex-mediated inflammatory cytokine elaboration in monocytes. In collagen-induced arthritis (CIA) rat models, treatment with oral GDC-0834 demonstrated robust anti-arthritis. GDC-0834 was reported to be extensively metabolized by aldehyde oxidase and carboxylesterase via amide hydrolysis.
Originator
Approval Year
PubMed
| Title | Date | PubMed |
|---|---|---|
| Antiarthritis effect of a novel Bruton's tyrosine kinase (BTK) inhibitor in rat collagen-induced arthritis and mechanism-based pharmacokinetic/pharmacodynamic modeling: relationships between inhibition of BTK phosphorylation and efficacy. | 2011 Jul |
|
| Significant species difference in amide hydrolysis of GDC-0834, a novel potent and selective Bruton's tyrosine kinase inhibitor. | 2011 Oct |
|
| Tyrosine kinase inhibitors as potential drugs for B-cell lymphoid malignancies and autoimmune disorders. | 2012 Jul |
|
| Validation and application of a liquid chromatography-tandem mass spectrometric method for the determination of GDC-0834 and its metabolite in human plasma using semi-automated 96-well protein precipitation. | 2012 Nov |
|
| Ibrutinib and novel BTK inhibitors in clinical development. | 2013 Aug 19 |
|
| Potent and selective Bruton's tyrosine kinase inhibitors: discovery of GDC-0834. | 2015 Mar 15 |
Sample Use Guides
In collagen-induced arthritis (CIA) rat models, treatment with oral GDC-0834 dosed at 30-100 mg/kg demonstrated robust anti-arthritis effect characterized by significant dose-dependent reduction in ankle swelling, and accompanied by potent inhibition of autophosphorylation of BTK.
Pharmacokinetics (PK) results of a recent phase I study of GDC-0834 (orally at 35 and 105 mg) in healthy volunteers showed that the drug is heavily metabolized by the liver to an inactive metabolite via amide hydrolysis.
Route of Administration:
Oral
| Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 16 01:56:57 GMT 2023
by
admin
on
Sat Dec 16 01:56:57 GMT 2023
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| Record UNII |
FM7JG3L4SR
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| Record Status |
Validated (UNII)
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| Record Version |
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