Target General Infomation
Target ID
T08123 (Former ID: TTDI03347)
Target Name
Leucine-rich repeat kinase 2 (LRRK2)
Synonyms
PARK8; Leucine-rich repeat serine/threonine-protein kinase 2; Dardarin
Gene Name
LRRK2
Target Type
Clinical trial target
[1]
Disease [+] 1 Target-related Diseases +
1 Parkinsonism [ICD-11: 8A00]
Function
Positively regulates autophagy through a calcium-dependent activation of the CaMKK/AMPK signaling pathway. The process involves activation of nicotinic acid adenine dinucleotide phosphate (NAADP) receptors, increase in lysosomal pH, and calcium release from lysosomes. 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. Regulates neuronal process morphology in the intact central nervous system (CNS). Plays a role in synaptic vesicle trafficking. Phosphorylates PRDX3. Has GTPase activity. May play a role in the phosphorylation of proteins central to Parkinson disease. Plays an important role in recuiting SEC16A to endoplasmic reticulum exit sites (ERES) and in regulating ER to Golgi vesicle-mediated transport and ERES organization.
BioChemical Class
Kinase
UniProt ID
LRRK2_HUMAN
EC Number
EC 2.7.11.1
Sequence
MASGSCQGCEEDEETLKKLIVRLNNVQEGKQIETLVQILEDLLVFTYSERASKLFQGKNI
HVPLLIVLDSYMRVASVQQVGWSLLCKLIEVCPGTMQSLMGPQDVGNDWEVLGVHQLILK
MLTVHNASVNLSVIGLKTLDLLLTSGKITLLILDEESDIFMLIFDAMHSFPANDEVQKLG
CKALHVLFERVSEEQLTEFVENKDYMILLSALTNFKDEEEIVLHVLHCLHSLAIPCNNVE
VLMSGNVRCYNIVVEAMKAFPMSERIQEVSCCLLHRLTLGNFFNILVLNEVHEFVVKAVQ
QYPENAALQISALSCLALLTETIFLNQDLEEKNENQENDDEGEEDKLFWLEACYKALTWH
RKNKHVQEAACWALNNLLMYQNSLHEKIGDEDGHFPAHREVMLSMLMHSSSKEVFQASAN
ALSTLLEQNVNFRKILLSKGIHLNVLELMQKHIHSPEVAESGCKMLNHLFEGSNTSLDIM
AAVVPKILTVMKRHETSLPVQLEALRAILHFIVPGMPEESREDTEFHHKLNMVKKQCFKN
DIHKLVLAALNRFIGNPGIQKCGLKVISSIVHFPDALEMLSLEGAMDSVLHTLQMYPDDQ
EIQCLGLSLIGYLITKKNVFIGTGHLLAKILVSSLYRFKDVAEIQTKGFQTILAILKLSA
SFSKLLVHHSFDLVIFHQMSSNIMEQKDQQFLNLCCKCFAKVAMDDYLKNVMLERACDQN
NSIMVECLLLLGADANQAKEGSSLICQVCEKESSPKLVELLLNSGSREQDVRKALTISIG
KGDSQIISLLLRRLALDVANNSICLGGFCIGKVEPSWLGPLFPDKTSNLRKQTNIASTLA
RMVIRYQMKSAVEEGTASGSDGNFSEDVLSKFDEWTFIPDSSMDSVFAQSDDLDSEGSEG
SFLVKKKSNSISVGEFYRDAVLQRCSPNLQRHSNSLGPIFDHEDLLKRKRKILSSDDSLR
SSKLQSHMRHSDSISSLASEREYITSLDLSANELRDIDALSQKCCISVHLEHLEKLELHQ
NALTSFPQQLCETLKSLTHLDLHSNKFTSFPSYLLKMSCIANLDVSRNDIGPSVVLDPTV
KCPTLKQFNLSYNQLSFVPENLTDVVEKLEQLILEGNKISGICSPLRLKELKILNLSKNH
ISSLSENFLEACPKVESFSARMNFLAAMPFLPPSMTILKLSQNKFSCIPEAILNLPHLRS
LDMSSNDIQYLPGPAHWKSLNLRELLFSHNQISILDLSEKAYLWSRVEKLHLSHNKLKEI
PPEIGCLENLTSLDVSYNLELRSFPNEMGKLSKIWDLPLDELHLNFDFKHIGCKAKDIIR
FLQQRLKKAVPYNRMKLMIVGNTGSGKTTLLQQLMKTKKSDLGMQSATVGIDVKDWPIQI
RDKRKRDLVLNVWDFAGREEFYSTHPHFMTQRALYLAVYDLSKGQAEVDAMKPWLFNIKA
RASSSPVILVGTHLDVSDEKQRKACMSKITKELLNKRGFPAIRDYHFVNATEESDALAKL
RKTIINESLNFKIRDQLVVGQLIPDCYVELEKIILSERKNVPIEFPVIDRKRLLQLVREN
QLQLDENELPHAVHFLNESGVLLHFQDPALQLSDLYFVEPKWLCKIMAQILTVKVEGCPK
HPKGIISRRDVEKFLSKKRKFPKNYMSQYFKLLEKFQIALPIGEEYLLVPSSLSDHRPVI
ELPHCENSEIIIRLYEMPYFPMGFWSRLINRLLEISPYMLSGRERALRPNRMYWRQGIYL
NWSPEAYCLVGSEVLDNHPESFLKITVPSCRKGCILLGQVVDHIDSLMEEWFPGLLEIDI
CGEGETLLKKWALYSFNDGEEHQKILLDDLMKKAEEGDLLVNPDQPRLTIPISQIAPDLI
LADLPRNIMLNNDELEFEQAPEFLLGDGSFGSVYRAAYEGEEVAVKIFNKHTSLRLLRQE
LVVLCHLHHPSLISLLAAGIRPRMLVMELASKGSLDRLLQQDKASLTRTLQHRIALHVAD
GLRYLHSAMIIYRDLKPHNVLLFTLYPNAAIIAKIADYGIAQYCCRMGIKTSEGTPGFRA
PEVARGNVIYNQQADVYSFGLLLYDILTTGGRIVEGLKFPNEFDELEIQGKLPDPVKEYG
CAPWPMVEKLIKQCLKENPQERPTSAQVFDILNSAELVCLTRRILLPKNVIVECMVATHH
NSRNASIWLGCGHTDRGQLSFLDLNTEGYTSEEVADSRILCLALVHLPVEKESWIVSGTQ
SGTLLVINTEDGKKRHTLEKMTDSVTCLYCNSFSKQSKQKNFLLVGTADGKLAIFEDKTV
KLKGAAPLKILNIGNVSTPLMCLSESTNSTERNVMWGGCGTKIFSFSNDFTIQKLIETRT
SQLFSYAAFSDSNIITVVVDTALYIAKQNSPVVEVWDKKTEKLCGLIDCVHFLREVMVKE
NKESKHKMSYSGRVKTLCLQKNTALWIGTGGGHILLLDLSTRRLIRVIYNFCNSVRVMMT
AQLGSLKNVMLVLGYNRKNTEGTQKQKEIQSCLTVWDINLPHEVQNLEKHIEVRKELAEK
MRRTSVE
Drugs and Modes of Action
Clinical Trial Drug(s) [+] 2 Clinical Trial Drugs +
1 DNL151 Drug Info Phase 1 Parkinson disease [1]
2 DNL201 Drug Info Phase 1 Parkinson disease [1]
Mode of Action [+] 1 Modes of Action +
Inhibitor [+] 40 Inhibitor drugs +
1 DNL151 Drug Info [1]
2 DNL201 Drug Info [1]
3 Aminopyridine derivative 2 Drug Info [2]
4 Aminopyridine derivative 3 Drug Info [2]
5 Azaindazole derivative 1 Drug Info [2]
6 Azaindazole derivative 2 Drug Info [2]
7 Azaindazole derivative 3 Drug Info [2]
8 Azaindazole derivative 4 Drug Info [2]
9 Bidentate ligands of Markush derivative 1 Drug Info [2]
10 Bidentate ligands of Markush derivative 2 Drug Info [2]
11 Fused thiophene derivative 1 Drug Info [2]
12 Hydrazide derivative 3 Drug Info [2]
13 Hydrazide derivative 4 Drug Info [2]
14 Hydrazide derivative 5 Drug Info [2]
15 Oxindole derivative 2 Drug Info [2]
16 Oxindole derivative 3 Drug Info [2]
17 Oxindole derivative 4 Drug Info [2]
18 PMID28117607-Compound-20 Drug Info [2]
19 PMID28117607-Compound-21 Drug Info [2]
20 PMID28117607-Compound-4 Drug Info [2]
21 PMID28117607-Compound-5 Drug Info [2]
22 PMID28117607-Compound-6 Drug Info [2]
23 PMID28117607-Compound-7 Drug Info [2]
24 Pyridopyrimidinone derivative 1 Drug Info [2]
25 Pyridopyrimidinone derivative 2 Drug Info [2]
26 Pyridopyrimidinone derivative 3 Drug Info [2]
27 Pyrrolo-pyridazine derivative 1 Drug Info [2]
28 Pyrrolo-pyridine derivative 1 Drug Info [2]
29 Pyrrolo-pyridine derivative 2 Drug Info [2]
30 Pyrrolo-pyrimidine derivative 1 Drug Info [2]
31 Pyrrolo-pyrimidine derivative 10 Drug Info [2]
32 Pyrrolo-pyrimidine derivative 11 Drug Info [2]
33 Pyrrolo-pyrimidine derivative 8 Drug Info [2]
34 Pyrrolo-pyrimidine derivative 9 Drug Info [2]
35 GNE-7915 Drug Info [3]
36 GNE-9605 Drug Info [3]
37 HMS3229G13 Drug Info [4]
38 PF-06447475 Drug Info [5]
39 PF-06454589 Drug Info [5]
40 URMC-099 Drug Info [6]
Target Regulators
Target-regulating microRNAs
Target-interacting Proteins
References
REF 1 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
REF 2 Leucine-rich repeat kinase 2 inhibitors: a patent review (2014-2016).Expert Opin Ther Pat. 2017 Jun;27(6):667-676.
REF 3 Discovery of highly potent, selective, and brain-penetrant aminopyrazole leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors. J Med Chem. 2014 Feb 13;57(3):921-36.
REF 4 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2059).
REF 5 Discovery and preclinical profiling of 3-[4-(morpholin-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]benzonitrile (PF-06447475), a highly potent, selective, brain penetrant, and in vivo active LRRK2 kinase inhibitor. J Med Chem. 2015 Jan 8;58(1):419-32.
REF 6 Discovery, synthesis, and characterization of an orally bioavailable, brain penetrant inhibitor of mixed lineage kinase 3. J Med Chem. 2013 Oct 24;56(20):8032-48.

If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Wang and Dr. Li.