8e2m

Bruton's tyrosine kinase (BTK) with compound 13Bruton's tyrosine kinase (BTK) with compound 13

Structural highlights

8e2m is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.904Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Publication Abstract from PubMed

Bruton's tyrosine kinase (BTK) is a Tec family kinase that plays an essential role in B-cell receptor (BCR) signaling as well as Fcgamma receptor signaling in leukocytes. Pharmacological inhibition of BTK has been shown to be effective in treating hematological malignancies and is hypothesized to provide an effective strategy for the treatment of autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus. We report the discovery and preclinical properties of JNJ-64264681 (13), a covalent, irreversible BTK inhibitor with potent whole blood activity and exceptional kinome selectivity. JNJ-64264681 demonstrated excellent oral efficacy in both cancer and autoimmune models with sustained in vivo target coverage amenable to once daily dosing and has advanced into human clinical studies to investigate safety and pharmacokinetics.

Discovery of JNJ-64264681: A Potent and Selective Covalent Inhibitor of Bruton's Tyrosine Kinase.,Tichenor MS, Wiener JJM, Rao NL, Bacani GM, Wei J, Pooley Deckhut C, Barbay JK, Kreutter KD, Chang L, Clancy KW, Murrey HE, Wang W, Ahn K, Huber M, Rex E, Coe KJ, Wu J, Rui H, Sepassi K, Gaudiano M, Bekkers M, Cornelissen I, Packman K, Seierstad M, Xiouras C, Bembenek SD, Alexander R, Milligan C, Balasubramanian S, Lebsack AD, Venable JD, Philippar U, Edwards JP, Hirst G J Med Chem. 2022 Nov 10;65(21):14326-14336. doi: 10.1021/acs.jmedchem.2c01026. , Epub 2022 Oct 31. PMID:36314537^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Tichenor MS, Wiener JJM, Rao NL, Bacani GM, Wei J, Pooley Deckhut C, Barbay JK, Kreutter KD, Chang L, Clancy KW, Murrey HE, Wang W, Ahn K, Huber M, Rex E, Coe KJ, Wu J, Rui H, Sepassi K, Gaudiano M, Bekkers M, Cornelissen I, Packman K, Seierstad M, Xiouras C, Bembenek SD, Alexander R, Milligan C, Balasubramanian S, Lebsack AD, Venable JD, Philippar U, Edwards JP, Hirst G. Discovery of JNJ-64264681: A Potent and Selective Covalent Inhibitor of Bruton's Tyrosine Kinase. J Med Chem. 2022 Nov 10;65(21):14326-14336. doi: 10.1021/acs.jmedchem.2c01026., Epub 2022 Oct 31. PMID:36314537 doi:http://dx.doi.org/10.1021/acs.jmedchem.2c01026

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OCA

[1] Tichenor MS, Wiener JJM, Rao NL, Bacani GM, Wei J, Pooley Deckhut C, Barbay JK, Kreutter KD, Chang L, Clancy KW, Murrey HE, Wang W, Ahn K, Huber M, Rex E, Coe KJ, Wu J, Rui H, Sepassi K, Gaudiano M, Bekkers M, Cornelissen I, Packman K, Seierstad M, Xiouras C, Bembenek SD, Alexander R, Milligan C, Balasubramanian S, Lebsack AD, Venable JD, Philippar U, Edwards JP, Hirst G. Discovery of JNJ-64264681: A Potent and Selective Covalent Inhibitor of Bruton's Tyrosine Kinase. J Med Chem. 2022 Nov 10;65(21):14326-14336. doi: 10.1021/acs.jmedchem.2c01026., Epub 2022 Oct 31. PMID:36314537 doi:http://dx.doi.org/10.1021/acs.jmedchem.2c01026

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