GDC-0834
WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#:406101
CAS#:1133432-46-8
Description:GDC-0834 is a potent and selective inhibitor of Bruton's tyrosine kinase (BTK), investigated as a potential treatment for rheumatoid arthritis. In vitro metabolite identification studies in hepatocytes revealed predominant formation of an inactive metabolite (M1) via amide hydrolysis in human.GDC-0834 was shown to be a potent reversible inhibitor of six known Aldehyde oxidase (AO)substrates with IC50 values ranging from 0.86 to 1.87 μM. Additionally, in silico modeling studies suggest that GDC-0834 is capable of binding in the active site of AO with the amide bond of GDC-0834 near the molybdenum cofactor (MoCo), orientated in such a way to enable potential nucleophilic attack on the carbonyl of the amide bond by the hydroxyl of MoCo. Together, the in vitro and in silico results suggest the involvement of AO in the amide hydrolysis of GDC-0834.
Price and Availability
GDC-0834 is not in stock, but may be available through custom synthesis. For cost-effective reason, minimum 1 gram order is requested. The product will be characterized by NMR, HPLC and MS analysis. Purity (HPLC) is usually >98%. CoA, QC data, MSDS will be provided when product is successfully made. The estimated lead time is 2-3 months. Please send email to sales@medkoo.com to inquire quote.
Chemical Structure
Theoretical Analysis
MedKoo Cat#: 406101Name: GDC-0834CAS#: 1133432-46-8Chemical Formula: C33H36N6O3SExact Mass: 596.25696Molecular Weight: 596.74Elemental Analysis: C, 66.42; H, 6.08; N, 14.08; O, 8.04; S, 5.37
Synonym:GDC0834; GDC-0834; GDC 0834.
IUPAC/Chemical Name:(R)-N-(3-(6-((4-(1,4-dimethyl-3-oxopiperazin-2-yl)phenyl)amino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide
InChi Key:CDOOFZZILLRUQH-GDLZYMKVSA-N
InChi Code: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
SMILES Code:O=C(C1=CC(CCCC2)=C2S1)NC3=CC=CC(C(N=C4NC5=CC=C([C@H]6N(C)CCN(C)C6=O)C=C5)=CN(C)C4=O)=C3C
Technical Data
Additional Information
References
1: Sodhi JK, Wong S, Kirkpatrick DS, Liu L, Khojasteh SC, Hop CE, Barr JT, JonesJP, Halladay JS. A novel reaction mediated by human aldehyde oxidase: amide hydrolysis of GDC-0834. Drug Metab Dispos. 2015 Jun;43(6):908-15. doi: 10.1124/dmd.114.061804. Epub 2015 Apr 6. PubMed PMID: 25845827; PubMed Central PMCID: PMC4429680.
2: Young WB, Barbosa J, Blomgren P, Bremer MC, Crawford JJ, Dambach D, Gallion S, Hymowitz SG, Kropf JE, Lee SH, Liu L, Lubach JW, Macaluso J, Maciejewski P, Maurer B, Mitchell SA, Ortwine DF, Di Paolo J, Reif K, Scheerens H, Schmitt A, Sowell CG, Wang X, Wong H, Xiong JM, Xu J, Zhao Z, Currie KS. Potent and selective Bruton"s tyrosine kinase inhibitors: discovery of GDC-0834. Bioorg MedChem Lett. 2015 Mar 15;25(6):1333-7. doi: 10.1016/j.bmcl.2015.01.032. Epub 2015 Feb 7. PubMed PMID: 25701252.
3: Akinleye A, Chen Y, Mukhi N, Song Y, Liu D. Ibrutinib and novel BTK inhibitors in clinical development. J Hematol Oncol. 2013 Aug 19;6:59. doi: 10.1186/1756-8722-6-59. Review. PubMed PMID: 23958373; PubMed Central PMCID: PMC3751776.
4: Robak T, Robak E. Tyrosine kinase inhibitors as potential drugs for B-cell lymphoid malignancies and autoimmune disorders. Expert Opin Investig Drugs. 2012Jul;21(7):921-47. doi: 10.1517/13543784.2012.685650. Epub 2012 May 22. Review. PubMed PMID: 22612424.
5: Shin YG, Jones SA, Murakami SC, Liu L, Wong H, Buonarati MH, Hop CE. 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. Biomed Chromatogr. 2012 Nov;26(11):1444-51. doi: 10.1002/bmc.2716. Epub 2012 Feb 7. PubMed PMID: 22311651.
6: Liu L, Halladay JS, Shin Y, Wong S, Coraggio M, La H, Baumgardner M, Le H, Gopaul S, Boggs J, Kuebler P, Davis JC Jr, Liao XC, Lubach JW, Deese A, Sowell CG, Currie KS, Young WB, Khojasteh SC, Hop CE, Wong H. Significant species difference in amide hydrolysis of GDC-0834, a novel potent and selective Bruton"s tyrosine kinase inhibitor. Drug Metab Dispos. 2011 Oct;39(10):1840-9. doi: 10.1124/dmd.111.040840. Epub 2011 Jul 8. PubMed PMID: 21742900.
7: Liu L, Di Paolo J, Barbosa J, Rong H, Reif K, Wong H. Antiarthritis effect ofa 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. J Pharmacol Exp Ther. 2011 Jul;338(1):154-63. doi: 10.1124/jpet.111.181545. Epub 2011 Apr 26. PubMed PMID: 21521773.
