regulation of ATP:ADP antiporter activity / ripoptosome assembly / positive regulation of interleukin-6-mediated signaling pathway / positive regulation of miRNA processing / ripoptosome assembly involved in necroptotic process / death domain binding / ripoptosome / Defective RIPK1-mediated regulated necrosis / TRIF-mediated programmed cell death / TLR3-mediated TICAM1-dependent programmed cell death ...regulation of ATP:ADP antiporter activity / ripoptosome assembly / positive regulation of interleukin-6-mediated signaling pathway / positive regulation of miRNA processing / ripoptosome assembly involved in necroptotic process / death domain binding / ripoptosome / Defective RIPK1-mediated regulated necrosis / TRIF-mediated programmed cell death / TLR3-mediated TICAM1-dependent programmed cell death / Microbial modulation of RIPK1-mediated regulated necrosis / Regulation by c-FLIP / CASP8 activity is inhibited / Dimerization of procaspase-8 / programmed necrotic cell death / TNF signaling / Caspase activation via Death Receptors in the presence of ligand / T cell apoptotic process / SARS-CoV-1-mediated effects on programmed cell death / positive regulation of macrophage differentiation / necroptotic signaling pathway / JUN kinase kinase kinase activity / peptidyl-serine autophosphorylation / NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 / positive regulation of necroptotic process / RIP-mediated NFkB activation via ZBP1 / death-inducing signaling complex / negative regulation of necroptotic process / positive regulation of tumor necrosis factor-mediated signaling pathway / death receptor binding / positive regulation of extrinsic apoptotic signaling pathway / positive regulation of programmed cell death / positive regulation of programmed necrotic cell death / TRP channels / TNFR1-induced proapoptotic signaling / RIPK1-mediated regulated necrosis / positive regulation of execution phase of apoptosis / necroptotic process / negative regulation of extrinsic apoptotic signaling pathway in absence of ligand / response to tumor necrosis factor / signaling adaptor activity / extrinsic apoptotic signaling pathway / negative regulation of canonical NF-kappaB signal transduction / tumor necrosis factor-mediated signaling pathway / TICAM1, RIP1-mediated IKK complex recruitment / IKK complex recruitment mediated by RIP1 / TNFR1-induced NF-kappa-B signaling pathway / positive regulation of interleukin-8 production / negative regulation of extrinsic apoptotic signaling pathway / Regulation of TNFR1 signaling / positive regulation of JNK cascade / protein catabolic process / positive regulation of non-canonical NF-kappaB signal transduction / Regulation of necroptotic cell death / cellular response to growth factor stimulus / cellular response to hydrogen peroxide / positive regulation of inflammatory response / positive regulation of reactive oxygen species metabolic process / positive regulation of neuron apoptotic process / positive regulation of tumor necrosis factor production / Ovarian tumor domain proteases / cellular response to tumor necrosis factor / positive regulation of NF-kappaB transcription factor activity / positive regulation of canonical NF-kappaB signal transduction / Potential therapeutics for SARS / protein autophosphorylation / response to oxidative stress / receptor complex / amyloid fibril formation / endosome membrane / non-specific serine/threonine protein kinase / protein kinase activity / Ub-specific processing proteases / intracellular signal transduction / positive regulation of protein phosphorylation / inflammatory response / positive regulation of apoptotic process / protein serine kinase activity / protein serine/threonine kinase activity / ubiquitin protein ligase binding / positive regulation of gene expression / negative regulation of apoptotic process / protein-containing complex binding / apoptotic process / positive regulation of transcription by RNA polymerase II / protein homodimerization activity / protein-containing complex / mitochondrion / ATP binding / identical protein binding / plasma membrane / cytosol Similarity search - Function
RIP1, Death domain / Death domain profile. / DEATH domain, found in proteins involved in cell death (apoptosis). / Death domain / : / Death domain / Death-like domain superfamily / Serine-threonine/tyrosine-protein kinase, catalytic domain / Protein tyrosine and serine/threonine kinase / Serine/threonine-protein kinase, active site ...RIP1, Death domain / Death domain profile. / DEATH domain, found in proteins involved in cell death (apoptosis). / Death domain / : / Death domain / Death-like domain superfamily / Serine-threonine/tyrosine-protein kinase, catalytic domain / Protein tyrosine and serine/threonine kinase / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / Serine/Threonine protein kinases, catalytic domain / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily / 2-Layer Sandwich / Orthogonal Bundle / Mainly Alpha / Alpha Beta Similarity search - Domain/homology
Journal: J. Med. Chem. / Year: 2018 Title: Discovery of 7-Oxo-2,4,5,7-tetrahydro-6 H-pyrazolo[3,4- c]pyridine Derivatives as Potent, Orally Available, and Brain-Penetrating Receptor Interacting Protein 1 (RIP1) Kinase Inhibitors: ...Title: Discovery of 7-Oxo-2,4,5,7-tetrahydro-6 H-pyrazolo[3,4- c]pyridine Derivatives as Potent, Orally Available, and Brain-Penetrating Receptor Interacting Protein 1 (RIP1) Kinase Inhibitors: Analysis of Structure-Kinetic Relationships. Authors: Yoshikawa, M. / Saitoh, M. / Katoh, T. / Seki, T. / Bigi, S.V. / Shimizu, Y. / Ishii, T. / Okai, T. / Kuno, M. / Hattori, H. / Watanabe, E. / Saikatendu, K.S. / Zou, H. / Nakakariya, M. / ...Authors: Yoshikawa, M. / Saitoh, M. / Katoh, T. / Seki, T. / Bigi, S.V. / Shimizu, Y. / Ishii, T. / Okai, T. / Kuno, M. / Hattori, H. / Watanabe, E. / Saikatendu, K.S. / Zou, H. / Nakakariya, M. / Tatamiya, T. / Nakada, Y. / Yogo, T.
Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength
Wavelength: 0.97 Å / Relative weight: 1
Reflection
Resolution: 2.52→95.39 Å / Num. obs: 37759 / % possible obs: 99 % / Redundancy: 3.6 % / Net I/σ(I): 12.9
Reflection shell
Resolution: 2.52→2.58 Å
-
Processing
Software
Name
Version
Classification
REFMAC
5.8.0049
refinement
HKL-2000
datareduction
HKL-2000
datascaling
MOLREP
phasing
Refinement
Resolution: 2.52→95.39 Å / Cor.coef. Fo:Fc: 0.929 / Cor.coef. Fo:Fc free: 0.882 / SU B: 45.254 / SU ML: 0.419 / Cross valid method: THROUGHOUT / ESU R Free: 0.38 / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
Rfactor
Num. reflection
% reflection
Selection details
Rfree
0.29643
1976
5 %
RANDOM
Rwork
0.23625
-
-
-
obs
0.24554
37639
98.95 %
-
Solvent computation
Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å