- TRICYCLIC COMPOUNDS AS HPK1 INHIBITOR AND THE USE THEREOF
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Disclosed herein is a tricyclic compound of Formula (I), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, and pharmaceutical compositions comprising thereof. Also disclosed is a method of treating HPK1 related disorders or diseases by using the compound disclosed herein.
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Paragraph 0101; 0116; 0117
(2021/01/29)
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- PYRROLO[2,3-B]PYRIDINES AS HPK1 INHIBITOR AND USES THEREOF
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Disclosed herein is a compound of Formula (I), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, and pharmaceutical compositions comprising thereof. Also disclosed is a method of treating HPK1 related disorders or diseases by using the compound disclosed herein.
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Page/Page column 29-30
(2020/06/10)
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- From Pyrazolones to Azaindoles: Evolution of Active-Site SHP2 Inhibitors Based on Scaffold Hopping and Bioisosteric Replacement
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The tyrosine phosphatase SHP2 controls the activity of pivotal signaling pathways, including MAPK, JAK-STAT, and PI3K-Akt. Aberrant SHP2 activity leads to uncontrolled cell proliferation, tumorigenesis, and metastasis. SHP2 signaling was recently linked to drug resistance against cancer medications such as MEK and BRAF inhibitors. In this work, we present the development of a novel class of azaindole SHP2 inhibitors. We applied scaffold hopping and bioisosteric replacement concepts to eliminate unwanted structural motifs and to improve the inhibitor characteristics of the previously reported pyrazolone SHP2 inhibitors. The most potent azaindole 45 inhibits SHP2 with an IC50 = 0.031 μM in an enzymatic assay and with an IC50 = 2.6 μM in human pancreas cells (HPAF-II). Evaluation in a series of cellular assays for metastasis and drug resistance demonstrated efficient SHP2 blockade. Finally, 45 inhibited proliferation of two cancer cell lines that are resistant to cancer drugs and diminished ERK signaling.
- Mostinski, Yelena,Heynen, Guus J. J. E.,López-Alberca, Maria Pascual,Paul, Jerome,Miksche, Sandra,Radetzki, Silke,Schaller, David,Shanina, Elena,Seyffarth, Carola,Kolomeets, Yuliya,Ziebart, Nandor,De Schryver, Judith,Oestreich, Sylvia,Neuenschwander, Martin,Roske, Yvette,Heinemann, Udo,Rademacher, Christoph,Volkamer, Andrea,Von Kries, Jens Peter,Birchmeier, Walter,Nazaré, Marc
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supporting information
p. 14780 - 14804
(2020/12/23)
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- COMPOUNDS AND METHODS FOR KINASE MODULATION, AND INDICATIONS THEREFOR
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Compounds of Formula I: or a pharmaceutically acceptable salt, a solvate, a tautomer, an isomer or a deuterated analog thereof, wherein R1, R2, Q1, Q2, and Q3, are described in this disclosure, compositions thereof, and methods and uses thereof.
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Paragraph 0556; 0559; 0560
(2016/11/24)
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