General Information of the Protein
Protein ID
PT06768
Protein Name
Leucine-rich repeat serine/threonine-protein kinase 2
Gene Name
LRRK2
Sequence
MASGACQGCEEEEEEEALKKLIVRLNNVQEGKQIETLLQLLEDMLVFTYSDRASKLFEDKNFHVPLLIVLDSYMRVASVQQAGWSLLCKLIEVCPGTLQSLIGPQDIGNDWEVLGIHRLILKMLTVHHANVNLSIVGLKALDLLLDSGKLTLLILDEECDIFLLIFDAMHRYSANDEVQKLGCKALHVLFERVSEEQLTEFVENKDYTILLSTFGSFRRDKEIVYHVLCCLHSLAVTCSNVEVLMSGNVRCYNLVVEAMKAFPTNENIQEVSCSLFQKLTLGNFFNILVLNEVHVFVVKAVRQYPENAALQISALSCLALLTETIFLNQDLEERSETQEQSEEEDSEKLFWLEPCYKALVRHRKDKHVQEAACWALNNLLMYQNSLHEKIGDEDGQFPAHREVMLSMLMHSSSKDVFQAAAHALSTLLEQNVNFRKILLAKGVYLNVLELMQKHAHAPEVAESGCKMLSHLFEGSNPSLDTMAAVVPKILTVMKAHGTSLSVQLEALRAILHFVVPGLLEESREDSQCRPNVLRKQCFRTDIHKLVLVALNRFIGNPGIQKCGLKVISSLAHLPDATETLSLQGAVDSVLHTLQMYPDDQEIQCLGLHLMGCLMTKKNFCIGTGHLLAKILASTLQRFKDVAEVQTTGLQTTLSILELSVSFSKLLVHYSFDVVIFHQMSSSVVEQKDEQFLNLCCKCFAKVAVDDELKNTMLERACDQNNSIMVECLLLLGADANQVKGATSLIYQVCEKESSPKLVELLLNGGCREQDVRKALTVSIQKGDSQVISLLLRKLALDLANNSICLGGFGIGKIDPSWLGPLFPDKSSNLRKQTNTGSVLARKVLRYQMRNTLQEGVASGSDGKFSEDALAKFGEWTFIPDSSMDSVFGQSDDLDSEGSESSFLVKRKSNSISVGEVYRDLALQRCSPNAQRHSNSLGPVFDHEDLLRRKRKILSSDESLRSSRLPSHMRQSDSSSSLASEREHITSLDLSANELKDIDALSQKCCLSSHLEHLTKLELHQNSLTSFPQQLCETLKCLIHLDLHSNKFTSFPSFVLKMPRITNLDASRNDIGPTVVLDPAMKCPSLKQLNLSYNQLSSIPENLAQVVEKLEQLLLEGNKISGICSPLSLKELKILNLSKNHIPSLPGDFLEACSKVESFSARMNFLAAMPALPSSITSLKLSQNSFTCIPEAIFSLPHLRSLDMSHNNIECLPGPAHWKSLNLRELIFSKNQISTLDFSENPHVWSRVEKLHLSHNKLKEIPPEIGCLENLTSLDVSYNLELRSFPNEMGKLSKIWDLPLDGLHLNFDFKHVGCKAKDIIRFLQQRLKKAVPYNRMKLMIVGNTGSGKTTLLQQLMKMKKPELGMQGATVGIDVRDWSIQIRGKRRKDLVLNVWDFAGREEFYSTHPHFMTQRALYLAVYDLSKGQAEVDAMKPWLFNIKARASSSPVILVGTHLDVSDEKQRKACISKITKELLNKRGFPTIRDYHFVNATEESDALAKLRKTIINESLNFKIRDQPVVGQLIPDCYVELEKIILSERKAVPTEFPVINRKHLLQLVNEHQLQLDENELPHAVHFLNESGVLLHFQDPALQLSDLYFVEPKWLCKVMAQILTVKVDGCLKHPKGIISRRDVEKFLSKKKRFPKNYMMQYFKLLEKFQIALPIGEEYLLVPSSLSDHRPVIELPHCENSEIIIRLYEMPYFPMGFWSRLINRLLEISPFMLSGRERALRPNRMYWRQGIYLNWSPEAYCLVGSEVLDNRPESFLKITVPSCRKGCILLGRVVDHIDSLMEEWFPGLLEIDICGEGETLLKKWALYSFNDGEEHQKILLDELMKKAEEGDLLINPDQPRLTIPISQIAPDLILADLPRNIMLNNDELEFEEAPEFLLGDGSFGSVYRAAYEGEEVAVKIFNKHTSLRLLRQELVVLCHLHHPSLISLLAAGIRPRMLVMELASKGSLDRLLQQDKASLTRTLQHRIALHVADGLRYLHSAMIIYRDLKPHNVLLFTLYPNAAIIAKIADYGIAQYCCRMGIKTSEGTPGFRAPEVARGNVIYNQQADVYSFGLLLHDIWTTGSRIMEGLRFPNEFDELAIQGKLPDPVKEYGCAPWPMVEKLITKCLKENPQERPTSAQVFDILNSAELICLMRHILIPKNIIVECMVATNLNSKSATLWLGCGNTEKGQLSLFDLNTERYSYEEVADSRILCLALVHLAAEKESWVVCGTQSGALLVINVEEETKRHTLEKMTDSVTCLHCNSLAKQSKQSNFLLVGTADGNLMIFEDKAVKCKGAAPLKTLHIGDVSTPLMCLSESLNSSERHITWGGCGTKVFSFSNDFTIQKLIETKTNQLFSYAAFSDSNIIALAVDTALYIAKKNSPVVEVWDKKTEKLCELIDCVHFLKEVMVKLNKESKHQLSYSGRVKALCLQKNTALWIGTGGGHILLLDLSTRRVIRTIHNFCDSVRAMATAQLGSLKNVMLVLGYKRKSTEGIQEQKEIQSCLSIWDLNLPHEVQNLEKHIEVRTELADKMRKTSVE
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Organism
Mus musculus, Mouse
Protein Classification
Enzyme
>
Kinase
>
Protein Kinase
>
TKL protein kinase group
>
TKL protein kinase LRRK family
Function
Serine/threonine-protein kinase which phosphorylates a broad range of proteins involved in multiple processes such as neuronal plasticity, innate immunity, autophagy, and vesicle trafficking (PubMed:26824392, PubMed:29125462, PubMed:28720718, PubMed:30398148, PubMed:29212815). Is a key regulator of RAB GTPases by regulating the GTP/GDP exchange and interaction partners of RABs through phosphorylation (PubMed:26824392, PubMed:28720718, PubMed:30398148, PubMed:29212815, PubMed:29125462). Phosphorylates RAB3A, RAB3B, RAB3C, RAB3D, RAB8A, RAB8B, RAB10, RAB12, RAB35, and RAB43 (PubMed:26824392, PubMed:28720718, PubMed:30398148, PubMed:29212815). Regulates the RAB3IP-catalyzed GDP/GTP exchange for RAB8A through the phosphorylation of 'Thr-72' on RAB8A (By similarity). Inhibits the interaction between RAB8A and GDI1 and/or GDI2 by phosphorylating 'Thr-72' on RAB8A (By similarity). Regulates primary ciliogenesis through phosphorylation of RAB8A and RAB10, which promotes SHH signaling in the brain (PubMed:29125462, PubMed:30398148). Together with RAB29, plays a role in the retrograde trafficking pathway for recycling proteins, such as mannose-6-phosphate receptor (M6PR), between lysosomes and the Golgi apparatus in a retromer-dependent manner (By similarity). Regulates neuronal process morphology in the intact central nervous system (CNS) (By similarity). Plays an important role in recruiting SEC16A to endoplasmic reticulum exit sites (ERES) and in regulating ER to Golgi vesicle-mediated transport and ERES organization (PubMed:25201882). Positively regulates autophagy through a calcium-dependent activation of the CaMKK/AMPK signaling pathway (By similarity). The process involves activation of nicotinic acid adenine dinucleotide phosphate (NAADP) receptors, increase in lysosomal pH, and calcium release from lysosomes (By similarity). Phosphorylates PRDX3 (By similarity). By phosphorylating APP on 'Thr-743', which promotes the production and the nuclear translocation of the APP intracellular domain (AICD), regulates dopaminergic neuron apoptosis (PubMed:28720718). Acts as a positive regulator of innate immunity by mediating phosphorylation of RIPK2 downstream of NOD1 and NOD2, thereby enhancing RIPK2 activation (By similarity). Independent of its kinase activity, inhibits the proteasomal degradation of MAPT, thus promoting MAPT oligomerization and secretion (By similarity). In addition, has GTPase activity via its Roc domain which regulates LRKK2 kinase activity (By similarity).
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Uniprot ID
Primary ID:
Q5S006

Secondarily ID:
E9QNJ2
Q8BWG7
Q8BZJ6
Q8CI84
Q8K062
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Ensembl ID
ENSG00000188906
Subcellular Location
Cytoplasmic vesicle
Perikaryon
Cell projection
Axon
Cell projection
Dendrite
Golgi apparatus membrane
Endoplasmic reticulum membrane
Cytoplasmic vesicle
Secretory vesicle
Synaptic vesicle membrane
Endosome
Lysosome
Mitochondrion outer membrane
Cytoplasm
Cytoskeleton
Map of Molecular Bioactivity Related to the Protein
Map of Molecular Bioactivity Related to the Protein

Protein
Cell Line
Compound

Bioactivity Value:

<= 0.1 μM
> 0.1 μM and <= 10 μM
> 10 μM
Imprecise Activity
Table of Molecular Bioactivities Related to the Protein
Cell Line ID: CL000006 , HEK293
Compound ID Compound Name Compound Formula
CP0644312
cis-2,6-Dimethyl-4-(6-(5-(1-methylcyclopropoxy)-1H-indazol-3-yl)pyrimidin-4-yl)morpholine
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C21H25N5O2
 1
1
EC50 = 30 nM
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CP0572948
3-[2-ethyl-4-(5-methyl-3-pyridin-4-yl-1H-pyrazol-4-yl)phenyl]benzenesulfonamide
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C23H22N4O2S
 2
1
EC50 = 260 nM
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2
EC50 > 100000 nM
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CP0545474
3-[2-cyclopropyl-4-[5-methyl-3-(2-methylpyridin-4-yl)-1H-pyrazol-4-yl]phenyl]benzenesulfonamide
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C25H24N4O2S
 2
1
EC50 = 280 nM
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2
EC50 = 5400 nM
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CP0543342
3-[4-[5-methyl-3-(2-morpholin-4-ylpyridin-4-yl)-1H-pyrazol-4-yl]phenyl]benzenesulfonamide
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C25H25N5O3S
 2
1
EC50 = 290 nM
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2
EC50 > 100000 nM
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CP0545472
3-[4-[5-(2-morpholin-4-ylpyridin-4-yl)-1H-pyrazol-4-yl]phenyl]benzenesulfonamide
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C24H23N5O3S
 1
1
EC50 = 340 nM
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CP0540375
3-[2-cyclopropyl-4-(5-methyl-3-pyridin-4-yl-1H-pyrazol-4-yl)phenyl]benzenesulfonamide
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C24H22N4O2S
 2
1
EC50 = 390 nM
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2
EC50 > 100000 nM
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CP0548058
3-[2,6-difluoro-4-(5-methyl-3-pyridin-4-yl-1H-pyrazol-4-yl)phenyl]benzenesulfonamide
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C21H16F2N4O2S
 1
1
EC50 = 390 nM
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CP0578500
3-[2-ethyl-4-(5-pyridin-4-yl-1H-pyrazol-4-yl)phenyl]benzenesulfonamide
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C22H20N4O2S
 1
1
EC50 = 600 nM
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CP0579366
3-[2-methyl-4-(5-methyl-3-pyridin-4-yl-1H-pyrazol-4-yl)phenyl]benzenesulfonamide
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C22H20N4O2S
 1
1
EC50 = 600 nM
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CP0577947
3-[2-fluoro-4-(5-methyl-3-pyridin-4-yl-1H-pyrazol-4-yl)phenyl]benzenesulfonamide
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C21H17FN4O2S
 1
1
EC50 = 690 nM
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CP0579422
3-[4-[3-(2-methoxypyridin-4-yl)-5-methyl-1H-pyrazol-4-yl]phenyl]benzenesulfonamide
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C22H20N4O3S
 1
1
EC50 = 750 nM
   TI
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CP0574644
3-[4-[3-(2,6-dimethylpyridin-4-yl)-5-methyl-1H-pyrazol-4-yl]phenyl]benzenesulfonamide
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C23H22N4O2S
 1
1
EC50 = 760 nM
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CP0545471
2,3-dimethyl-4-[4-[5-methyl-3-(2-morpholin-4-ylpyridin-4-yl)-1H-pyrazol-4-yl]phenyl]benzenesulfonamide
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C27H29N5O3S
 1
1
EC50 = 800 nM
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CP0575926
3-[4-[5-(2,6-dimethylpyridin-4-yl)-1H-pyrazol-4-yl]phenyl]benzenesulfonamide
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C22H20N4O2S
 1
1
EC50 = 920 nM
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CP0576280
3-[4-[5-methyl-3-(2-methylpyridin-4-yl)-1H-pyrazol-4-yl]phenyl]benzenesulfonamide
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C22H20N4O2S
 1
1
EC50 = 1080 nM
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CP0554483
3-[2-methoxy-4-(5-methyl-3-pyridin-4-yl-1H-pyrazol-4-yl)phenyl]benzenesulfonamide
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C22H20N4O3S
 1
1
EC50 = 1280 nM
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CP0579421
3-[4-[5-(2-methylpyridin-4-yl)-1H-pyrazol-4-yl]phenyl]benzenesulfonamide
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C21H18N4O2S
 1
1
EC50 = 1380 nM
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CP0575928
3-[2,6-dimethyl-4-(5-methyl-3-pyridin-4-yl-1H-pyrazol-4-yl)phenyl]benzenesulfonamide
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C23H22N4O2S
 1
1
EC50 = 1440 nM
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CP0579357
2,3-dimethyl-4-[4-[5-(2-morpholin-4-ylpyridin-4-yl)-1H-pyrazol-4-yl]phenyl]benzenesulfonamide
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C26H27N5O3S
 2
1
EC50 = 1500 nM
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2
EC50 = 76000 nM
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CP0579473
3-[4-(5-methyl-3-pyridin-4-yl-1H-pyrazol-4-yl)-2-propan-2-ylphenyl]benzenesulfonamide
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C24H24N4O2S
 1
1
EC50 = 1710 nM
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CP0578781
3-[4-(5-methyl-3-pyridin-4-yl-1H-pyrazol-4-yl)phenyl]benzenesulfonamide
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C21H18N4O2S
 2
1
EC50 = 2100 nM
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2
EC50 > 100000 nM
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CP0579358
3-[4-[5-(2-methoxypyridin-4-yl)-1H-pyrazol-4-yl]phenyl]benzenesulfonamide
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C21H18N4O3S
 1
1
EC50 = 2310 nM
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CP0577021
3-[2,3-difluoro-4-(5-methyl-3-pyridin-4-yl-1H-pyrazol-4-yl)phenyl]benzenesulfonamide
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C21H16F2N4O2S
 1
1
EC50 = 3120 nM
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CP0570308
4-methyl-3-[4-(5-methyl-3-pyridin-4-yl-1H-pyrazol-4-yl)phenyl]benzenesulfonamide
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C22H20N4O2S
 1
1
EC50 = 3200 nM
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CP0572949
3-[4-(5-methyl-3-pyridin-4-yl-1H-pyrazol-4-yl)-2-(trifluoromethyl)phenyl]benzenesulfonamide
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C22H17F3N4O2S
 1
1
EC50 = 4780 nM
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CP0579994
4-[5-methyl-4-[3-methyl-4-(3-methylsulfonylphenyl)phenyl]-1H-pyrazol-3-yl]pyridine
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C23H21N3O2S
 1
1
EC50 = 4900 nM
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CP0572967
3-[4-(5-pyridin-4-yl-1H-pyrazol-4-yl)phenyl]benzenesulfonamide
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C20H16N4O2S
 1
1
EC50 = 5100 nM
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CP0544064
2-methyl-3-[4-(5-methyl-3-pyridin-4-yl-1H-pyrazol-4-yl)phenyl]benzenesulfonamide
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C22H20N4O2S
 1
1
EC50 = 6400 nM
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CP0577215
3-[4-(5-phenyl-1H-pyrazol-4-yl)phenyl]benzenesulfonamide
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C21H17N3O2S
 1
1
EC50 = 12200 nM
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CP0580094
4-methyl-3-[4-(5-pyridin-4-yl-1H-pyrazol-4-yl)phenyl]benzenesulfonamide
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C21H18N4O2S
 1
1
EC50 = 12200 nM
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CP0545473
3-[3-methyl-4-(5-methyl-3-pyridin-4-yl-1H-pyrazol-4-yl)phenyl]benzenesulfonamide
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C22H20N4O2S
 1
1
EC50 = 13400 nM
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CP0548056
4-[2-ethyl-4-(5-methyl-3-pyridin-4-yl-1H-pyrazol-4-yl)phenyl]benzenesulfonamide
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C23H22N4O2S
 1
1
EC50 = 14300 nM
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CP0577255
4-[4-[3-(2,6-dimethylpyridin-4-yl)-5-methyl-1H-pyrazol-4-yl]phenyl]-2,3-dimethylbenzenesulfonamide
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C25H26N4O2S
 1
1
EC50 = 15000 nM
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CP0575925
3-[4-[3-pyridin-4-yl-5-(trifluoromethyl)-1H-pyrazol-4-yl]phenyl]benzenesulfonamide
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C21H15F3N4O2S
 1
1
EC50 = 16700 nM
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CP0579367
3-[2-cyano-4-(5-methyl-3-pyridin-4-yl-1H-pyrazol-4-yl)phenyl]benzenesulfonamide
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C22H17N5O2S
 1
1
EC50 = 19600 nM
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CP0577020
3-[2-methyl-4-(5-methyl-3-pyridin-4-yl-1H-pyrazol-4-yl)phenyl]benzamide
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C23H20N4O
 1
1
EC50 = 21700 nM
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CP0579356
2,3-dimethyl-4-[4-[5-methyl-3-(2-methylpyridin-4-yl)-1H-pyrazol-4-yl]phenyl]benzenesulfonamide
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C24H24N4O2S
 1
1
EC50 = 57000 nM
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CP0579420
2,3-dimethyl-4-[4-(5-pyridin-4-yl-1H-pyrazol-4-yl)phenyl]benzenesulfonamide
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C22H20N4O2S
 1
1
EC50 = 80000 nM
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CP0577216
3,4-dimethyl-5-[4-(5-methyl-3-pyridin-4-yl-1H-pyrazol-4-yl)phenyl]benzenesulfonamide
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C23H22N4O2S
 1
1
EC50 > 100000 nM
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CP0579355
2,3-dimethyl-4-[4-(5-methyl-3-pyridin-4-yl-1H-pyrazol-4-yl)phenyl]benzenesulfonamide
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C23H22N4O2S
 1
1
EC50 > 100000 nM
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Similar Protein(s) and Bioactivity Statistics
50% Identity
Protein ID Protein Name Protein Organism
PT01378 Leucine-rich repeat serine/threonine-protein kinase 2 Homo sapiens, Human