884497-46-5Relevant articles and documents
From off-to on-target: New BRAF-inhibitor-template-derived compounds selectively targeting mitogen activated protein kinase kinase 4 (MKK4)
Kl?vekorn, Philip,Pfaffenrot, Bent,Juchum, Michael,Selig, Roland,Albrecht, Wolfgang,Zender, Lars,Laufer, Stefan A.
supporting information, (2020/11/20)
The mitogen-activated protein kinase (MAP) kinase 4 (MKK4) was found to be a major regulator of liver regeneration and could be a valuable drug target addressing liver related diseases by restoring its intrinsic regenerative capacity. We report on the synthesis and optimization of novel MKK4 inhibitors following a target-hopping strategy from the FDA-approved BRAFV600E inhibitor PLX4032 (8). Applying an iterative multi-parameter optimization process we carved out essential structural features yielding in compounds with a low nanomolar affinity for MKK4 and excellent selectivity profiles against the main off-targets MKK7 and JNK1, which, upon relevant inhibition, would totally abrogate the pro-regenerative effect of MKK4 inhibition, as well as against the off-targets MAP4K5, ZAK and BRAF with selectivity factors ranging from 40 to 430 for our best-balanced compounds 70 and 73.
ΒETA-CATENIN AND B-CELL LYMPHOMA 9 (BCL9) INHIBITORS
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Page/Page column 37; 39; 104, (2020/05/21)
Disclosed are inhibitors for the β-catenin/BCL9 interaction. The inhibitors are selective for β-catenin/BCL9 over β-catenin/cadherin interactions. Methods of using the disclosed compounds to treat cancer are also disclosed.
FUSED TETRA OR PENTA-CYCLIC PYRIDOPHTHALAZINONES AS PARP INHIBITORS
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Paragraph 0227; 0231, (2017/12/01)
Provided are certain fused tetra or penta-cyclic compounds and salts thereof, compositions thereof, and methods of use thereof.
Aminoheteroaryl benzamides as kinase inhibitors
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Page/Page column 280; 282, (2016/02/15)
The present invention provides a compound of Formula (I) or a salt thereof; and therapeutic uses of these compounds. The present invention further provides pharmaceutical compositions comprising these compounds, and compositions comprising these compounds with a therapeutic co-agent.
THERAPEUTICALLY ACTIVE COMPOUNDS AND THEIR METHODS OF USE
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Page/Page column 68, (2015/02/19)
Provided are methods of treating a cancer characterized by the presence of a mutant allele of IDH1/2 comprising administering to a subject in need thereof a compound described here.
FUSED TETRA OR PENTA-CYCLIC PYRIDOPHTHALAZINONES AS PARP INHIBITORS
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Paragraph 0276, (2015/02/18)
Provided are certain fused tetra or penta-cyclic compounds and salts thereof, compositions thereof, and methods of use thereof.
THERAPEUTICALLY ACTIVE COMPOUNDS AND THEIR METHODS OF USE
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Page/Page column, (2015/02/19)
Provided are methods of treating a cancer characterized by the presence of a mutant allele of IDH1/2 comprising administering to a subject in need thereof a compound described here.
THERAPEUTICALLY ACTIVE COMPOUNDS AND USE THEREOF
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Page/Page column 69, (2015/02/19)
Provided are therapeutically active compounds and the use in manufacture of medicaments for treating a cancer characterized by the presence of a mutant allele of IDH1.
FUSED TETRA OR PENTA-CYCLIC PYRIDOPHTHALAZINONES AS PARP INHIBITORS
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Page/Page column 46; 47, (2013/07/19)
Provided are certain fused tetra or penta-cyclic compounds and salts thereof, compositions thereof, and methods of use thereof.
THERAPEUTICALLY ACTIVE COMPOSITIONS AND THEIR METHODS OF USE
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Page/Page column, (2013/07/31)
Provided are methods of treating a cancer characterized by the presence of a mutant allele of IDH1/2 comprising administering to a subject in need thereof a compound described here.