2-methyl-2-(3-methyl-4-((4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-1H-pyrazol-1-yl)propanenitrile: a leucine-rich repeat kinase 2 (LRRK2) inhibitor; structure in first source [MeSH]
| ID Source | ID |
|---|---|
| PubMed CID | 69093374 |
| CHEMBL ID | 3122113 |
| SCHEMBL ID | 4561063 |
| MeSH ID | M0593377 |
| Synonym |
|---|
| bdbm50448118 |
| S7367 |
| gne0877 |
| HY-15796 |
| 2-methyl-2-(3-methyl-4-(4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)-1h-pyrazol-1-yl)propanenitrile |
| CHEMBL3122113 , |
| 2-methyl-2-(3-methyl-4-((4-(methylamino)-5-(trifluoromethyl)-pyrimidin-2-yl)amino)-1h-pyrazol-1-yl)propanenitrile |
| 2-methyl-2-(3-methyl-4-((4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-1h-pyrazol-1-yl)propanenitrile |
| SCHEMBL4561063 |
| 1374828-69-9 |
| gne-0877 |
| compound 11 [pmid: 24354345] |
| dnl201 |
| dnl-201 |
| 2-methyl-2-[3-methyl-4-[[4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-yl]amino]pyrazol-1-yl]propanenitrile |
| gtpl9393 |
| 1h-pyrazole-1-acetonitrile, alpha,alpha,3-trimethyl-4-((4-(methylamino)-5-(trifluoromethyl)-2-pyrimidinyl)amino)- |
| unii-anghs285fg |
| AKOS027250747 |
| HMS3653E18 |
| gne 0877 |
| NCGC00386334-02 |
| 1h-pyrazole-1-acetonitrile, .alpha.,.alpha.,3-trimethyl-4-((4-(methylamino)-5-(trifluoromethyl)-2-pyrimidinyl)amino)- |
| ANGHS285FG , |
| SW220180-1 |
| FT-0716965 |
| mfcd28098661 |
| 2-methyl-2-(3-methyl-4-((4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-1h-pyrazol-1-yl)propanenitrile . |
| BCP09654 |
| AMY16361 |
| SB17007 |
| CCG-267909 |
| AT19318 |
| EX-A2062 |
| A886471 |
| MS-25163 |
| TVT , |
| 2-methyl-2-(3-methyl-4-{[4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}-1h-pyrazol-1-yl)propanenitrile |
| 2-methyl-2-[3-methyl-4-[[4-(methylamino)-5-(trifluoromethyl)-2-pyrimidinyl]amino]-1-pyrazolyl]propanenitrile |
| SY275739 |
| AC-35917 |
| 2-methyl-2-(3-methyl-4-{[4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}pyrazol-1-yl)propanenitrile |
| Protein | Taxonomy | Measurement | Average (mM) | Bioassay(s) |
|---|---|---|---|---|
| cytochrome P450 family 3 subfamily A polypeptide 4 | Homo sapiens (human) | Potency | 1.3450 | AID1645841 |
| G | Vesicular stomatitis virus | Potency | 7.5637 | AID1645842 |
| Interferon beta | Homo sapiens (human) | Potency | 7.5637 | AID1645842 |
| HLA class I histocompatibility antigen, B alpha chain | Homo sapiens (human) | Potency | 7.5637 | AID1645842 |
| Inositol hexakisphosphate kinase 1 | Homo sapiens (human) | Potency | 7.5637 | AID1645842 |
| cytochrome P450 2C9, partial | Homo sapiens (human) | Potency | 7.5637 | AID1645842 |
| Protein | Taxonomy | Measurement | Average (mM) | Bioassay(s) |
|---|---|---|---|---|
| Dual specificity protein kinase TTK | Homo sapiens (human) | Ki | 0.1500 | AID1071298 |
| Leucine-rich repeat serine/threonine-protein kinase 2 | Homo sapiens (human) | IC50 | 0.0030 | AID1071299 |
| Leucine-rich repeat serine/threonine-protein kinase 2 | Homo sapiens (human) | Ki | 0.0006 | AID1071300; AID1673916 |
| Assay ID | Title | Year | Journal | Article |
|---|---|---|---|---|
| AID1821424 | Efflux ratio of apparent permeability across basolateral to apical side over apical to basolateral side in human MDR1-transfected dog MDCKII-MDR1 cells at 0.1 to 1 uM measured after 3 hrs by LC/MS/MS analysis | 2022 | Journal of medicinal chemistry, 01-13, Volume: 65, Issue:1 ISSN: 1520-4804 | Structure-Guided Discovery of Aminoquinazolines as Brain-Penetrant and Selective LRRK2 Inhibitors. |
| AID1071256 | Unbound clearance in cynomolgus monkey at 1 mg/kg, po and 0.5 mg/kg, iv | 2014 | Journal of medicinal chemistry, Feb-13, Volume: 57, Issue:3 ISSN: 1520-4804 | Discovery of highly potent, selective, and brain-penetrant aminopyrazole leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors. |
| AID1071280 | Ratio of drug level in CSF to unbound drug level in plasma in Sprague-Dawley rat | 2014 | Journal of medicinal chemistry, Feb-13, Volume: 57, Issue:3 ISSN: 1520-4804 | Discovery of highly potent, selective, and brain-penetrant aminopyrazole leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors. |
| AID1071261 | In vivo inhibition of human LRRK2 G2019S Parkinson's disease mutant expressed in BAC mouse assessed as inhibition of autophosphorylation at Ser1292 in brain at 10 to 50 mg/kg, ip after 1 to 6 hrs | 2014 | Journal of medicinal chemistry, Feb-13, Volume: 57, Issue:3 ISSN: 1520-4804 | Discovery of highly potent, selective, and brain-penetrant aminopyrazole leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors. |
| AID1071286 | Selectivity ratio of Ki for TTK (unknown origin) to Ki for LRRK2 (unknown origin) | 2014 | Journal of medicinal chemistry, Feb-13, Volume: 57, Issue:3 ISSN: 1520-4804 | Discovery of highly potent, selective, and brain-penetrant aminopyrazole leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors. |
| AID1071288 | Inhibition of RSK3 (unknown origin) at 0.1 uM relative to control | 2014 | Journal of medicinal chemistry, Feb-13, Volume: 57, Issue:3 ISSN: 1520-4804 | Discovery of highly potent, selective, and brain-penetrant aminopyrazole leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors. |
| AID1673916 | Inhibition of LRRK2 G2019S mutant (unknown origin) | 2020 | Journal of medicinal chemistry, 10-22, Volume: 63, Issue:20 ISSN: 1520-4804 | Monomeric Targeted Protein Degraders. |
| AID1071293 | Drug metabolism in human hepatocytes assessed as glucuronidated parent compound level after 3 hrs | 2014 | Journal of medicinal chemistry, Feb-13, Volume: 57, Issue:3 ISSN: 1520-4804 | Discovery of highly potent, selective, and brain-penetrant aminopyrazole leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors. |
| AID1071279 | Reversible inhibition of CYP1A2 in human liver microsomes using phenacetin as substrate by mass spectrophotometric analysis | 2014 | Journal of medicinal chemistry, Feb-13, Volume: 57, Issue:3 ISSN: 1520-4804 | Discovery of highly potent, selective, and brain-penetrant aminopyrazole leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors. |
| AID1821470 | Unbound brain-to-plasma concentration ratio in non-human primates administered orally and measured after 120 mins by LC/MS/MS analysis | 2022 | Journal of medicinal chemistry, 01-13, Volume: 65, Issue:1 ISSN: 1520-4804 | Structure-Guided Discovery of Aminoquinazolines as Brain-Penetrant and Selective LRRK2 Inhibitors. |
| AID1071285 | Selectivity ratio of Ki for RSK2 (unknown origin) to Ki for LRRK2 (unknown origin) | 2014 | Journal of medicinal chemistry, Feb-13, Volume: 57, Issue:3 ISSN: 1520-4804 | Discovery of highly potent, selective, and brain-penetrant aminopyrazole leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors. |
| AID1071291 | Inhibition of aurora-B (unknown origin) at 0.1 uM relative to control | 2014 | Journal of medicinal chemistry, Feb-13, Volume: 57, Issue:3 ISSN: 1520-4804 | Discovery of highly potent, selective, and brain-penetrant aminopyrazole leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors. |
| AID1071289 | Inhibition of RSK2 (unknown origin) at 0.1 uM relative to control | 2014 | Journal of medicinal chemistry, Feb-13, Volume: 57, Issue:3 ISSN: 1520-4804 | Discovery of highly potent, selective, and brain-penetrant aminopyrazole leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors. |
| AID1071260 | Plasma protein binding in cynomolgus monkey at 5 uM after 4 hrs by equilibrium dialysis technique | 2014 | Journal of medicinal chemistry, Feb-13, Volume: 57, Issue:3 ISSN: 1520-4804 | Discovery of highly potent, selective, and brain-penetrant aminopyrazole leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors. |
| AID1071259 | Clearance in cynomolgus monkey hepatocytes at 1 uM by LC-MS/MS analysis | 2014 | Journal of medicinal chemistry, Feb-13, Volume: 57, Issue:3 ISSN: 1520-4804 | Discovery of highly potent, selective, and brain-penetrant aminopyrazole leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors. |
| AID1071297 | Clearance in human hepatocytes at 1 uM by LC-MS/MS analysis | 2014 | Journal of medicinal chemistry, Feb-13, Volume: 57, Issue:3 ISSN: 1520-4804 | Discovery of highly potent, selective, and brain-penetrant aminopyrazole leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors. |
| AID1071257 | Half life in cynomolgus monkey at 0.5 mg/kg, iv | 2014 | Journal of medicinal chemistry, Feb-13, Volume: 57, Issue:3 ISSN: 1520-4804 | Discovery of highly potent, selective, and brain-penetrant aminopyrazole leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors. |
| AID1071301 | Selectivity ratio of Ki for JAK2 (unknown origin) to Ki for LRRK2 (unknown origin) | 2014 | Journal of medicinal chemistry, Feb-13, Volume: 57, Issue:3 ISSN: 1520-4804 | Discovery of highly potent, selective, and brain-penetrant aminopyrazole leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors. |
| AID1071278 | Time dependent inhibition of CYP1A2 in human liver microsomes using phenacetin as substrate by HPLC-MS analysis | 2014 | Journal of medicinal chemistry, Feb-13, Volume: 57, Issue:3 ISSN: 1520-4804 | Discovery of highly potent, selective, and brain-penetrant aminopyrazole leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors. |
| AID1071282 | Oral bioavailability in Sprague-Dawley rat at 50 mg/kg | 2014 | Journal of medicinal chemistry, Feb-13, Volume: 57, Issue:3 ISSN: 1520-4804 | Discovery of highly potent, selective, and brain-penetrant aminopyrazole leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors. |
| AID1821425 | Unbound brain-to-plasma concentration ratio in rat at 2.5 uM incubated for 4 hrs by equilibrium dialysis method | 2022 | Journal of medicinal chemistry, 01-13, Volume: 65, Issue:1 ISSN: 1520-4804 | Structure-Guided Discovery of Aminoquinazolines as Brain-Penetrant and Selective LRRK2 Inhibitors. |
| AID1071276 | Induction of CYP1A2 in human hepatocytes | 2014 | Journal of medicinal chemistry, Feb-13, Volume: 57, Issue:3 ISSN: 1520-4804 | Discovery of highly potent, selective, and brain-penetrant aminopyrazole leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors. |
| AID1071277 | Induction of CYP3A4 in human hepatocytes | 2014 | Journal of medicinal chemistry, Feb-13, Volume: 57, Issue:3 ISSN: 1520-4804 | Discovery of highly potent, selective, and brain-penetrant aminopyrazole leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors. |
| AID1071299 | Inhibition of LRRK2 (unknown origin) phosphorylation by cell-based assay | 2014 | Journal of medicinal chemistry, Feb-13, Volume: 57, Issue:3 ISSN: 1520-4804 | Discovery of highly potent, selective, and brain-penetrant aminopyrazole leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors. |
| AID1071283 | Selectivity ratio of Ki for RSK3 (unknown origin) to Ki for LRRK2 (unknown origin) | 2014 | Journal of medicinal chemistry, Feb-13, Volume: 57, Issue:3 ISSN: 1520-4804 | Discovery of highly potent, selective, and brain-penetrant aminopyrazole leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors. |
| AID1071290 | Inhibition of RSK4 (unknown origin) at 0.1 uM relative to control | 2014 | Journal of medicinal chemistry, Feb-13, Volume: 57, Issue:3 ISSN: 1520-4804 | Discovery of highly potent, selective, and brain-penetrant aminopyrazole leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors. |
| AID1071258 | Clearance in cynomolgus monkey at 1 mg/kg, po and 0.5 mg/kg, iv | 2014 | Journal of medicinal chemistry, Feb-13, Volume: 57, Issue:3 ISSN: 1520-4804 | Discovery of highly potent, selective, and brain-penetrant aminopyrazole leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors. |
| AID1071300 | Inhibition of LRRK2 (unknown origin) | 2014 | Journal of medicinal chemistry, Feb-13, Volume: 57, Issue:3 ISSN: 1520-4804 | Discovery of highly potent, selective, and brain-penetrant aminopyrazole leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors. |
| AID1071275 | Induction of CYP2B6 in human hepatocytes | 2014 | Journal of medicinal chemistry, Feb-13, Volume: 57, Issue:3 ISSN: 1520-4804 | Discovery of highly potent, selective, and brain-penetrant aminopyrazole leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors. |
| AID1071253 | Drug metabolism in human liver microsomes assessed as glucuronidated parent compound level after 3 hrs | 2014 | Journal of medicinal chemistry, Feb-13, Volume: 57, Issue:3 ISSN: 1520-4804 | Discovery of highly potent, selective, and brain-penetrant aminopyrazole leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors. |
| AID1071298 | Inhibition of TTK (unknown origin) | 2014 | Journal of medicinal chemistry, Feb-13, Volume: 57, Issue:3 ISSN: 1520-4804 | Discovery of highly potent, selective, and brain-penetrant aminopyrazole leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors. |
| AID1071303 | Activity at human MDR1 transfected in MDCK cells assessed as efflux ratio of apparent permeability from basolateral to apical side over apical to basolateral side at 5 uM | 2014 | Journal of medicinal chemistry, Feb-13, Volume: 57, Issue:3 ISSN: 1520-4804 | Discovery of highly potent, selective, and brain-penetrant aminopyrazole leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors. |
| AID1071296 | Clearance in rat hepatocytes at 1 uM by LC-MS/MS analysis | 2014 | Journal of medicinal chemistry, Feb-13, Volume: 57, Issue:3 ISSN: 1520-4804 | Discovery of highly potent, selective, and brain-penetrant aminopyrazole leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors. |
| AID1071295 | Unbound clearance in Sprague-Dawley rat at 1 mg/kg, po and 0.5 mg/kg, iv | 2014 | Journal of medicinal chemistry, Feb-13, Volume: 57, Issue:3 ISSN: 1520-4804 | Discovery of highly potent, selective, and brain-penetrant aminopyrazole leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors. |
| AID1071294 | Clearance in Sprague-Dawley rat at 1 mg/kg, po and 0.5 mg/kg, iv | 2014 | Journal of medicinal chemistry, Feb-13, Volume: 57, Issue:3 ISSN: 1520-4804 | Discovery of highly potent, selective, and brain-penetrant aminopyrazole leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors. |
| AID1071255 | Ratio of drug level in CSF to unbound drug level in plasma in cynomolgus monkey | 2014 | Journal of medicinal chemistry, Feb-13, Volume: 57, Issue:3 ISSN: 1520-4804 | Discovery of highly potent, selective, and brain-penetrant aminopyrazole leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors. |
| AID1071287 | Selectivity ratio of Ki for aurora-B (unknown origin) to Ki for LRRK2 (unknown origin) | 2014 | Journal of medicinal chemistry, Feb-13, Volume: 57, Issue:3 ISSN: 1520-4804 | Discovery of highly potent, selective, and brain-penetrant aminopyrazole leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors. |
| AID1071284 | Selectivity ratio of Ki for RSK4 (unknown origin) to Ki for LRRK2 (unknown origin) | 2014 | Journal of medicinal chemistry, Feb-13, Volume: 57, Issue:3 ISSN: 1520-4804 | Discovery of highly potent, selective, and brain-penetrant aminopyrazole leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors. |
| AID1071302 | Thermodynamic solubility of the crystalline form of compound at pH 7.4 | 2014 | Journal of medicinal chemistry, Feb-13, Volume: 57, Issue:3 ISSN: 1520-4804 | Discovery of highly potent, selective, and brain-penetrant aminopyrazole leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors. |
| AID1071254 | Oral bioavailability in cynomolgus monkey at 1 mg/kg | 2014 | Journal of medicinal chemistry, Feb-13, Volume: 57, Issue:3 ISSN: 1520-4804 | Discovery of highly potent, selective, and brain-penetrant aminopyrazole leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors. |
| AID1071281 | Ratio of unbound drug level in brain to plasma in Sprague-Dawley rat | 2014 | Journal of medicinal chemistry, Feb-13, Volume: 57, Issue:3 ISSN: 1520-4804 | Discovery of highly potent, selective, and brain-penetrant aminopyrazole leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors. |
| AID1296008 | Cytotoxic Profiling of Annotated Libraries Using Quantitative High-Throughput Screening | 2020 | SLAS discovery : advancing life sciences R & D, 01, Volume: 25, Issue:1 ISSN: 2472-5560 | Cytotoxic Profiling of Annotated and Diverse Chemical Libraries Using Quantitative High-Throughput Screening. |
| AID1347160 | Primary screen NINDS Rhodamine qHTS for Zika virus inhibitors | 2020 | Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49 ISSN: 1091-6490 | Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors. |
| AID1346987 | P-glycoprotein substrates identified in KB-8-5-11 adenocarcinoma cell line, qHTS therapeutic library screen | 2019 | Molecular pharmacology, 11, Volume: 96, Issue:5 ISSN: 1521-0111 | A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein. |
| AID1346986 | P-glycoprotein substrates identified in KB-3-1 adenocarcinoma cell line, qHTS therapeutic library screen | 2019 | Molecular pharmacology, 11, Volume: 96, Issue:5 ISSN: 1521-0111 | A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein. |
| AID1347159 | Primary screen GU Rhodamine qHTS for Zika virus inhibitors: Unlinked NS2B-NS3 protease assay | 2020 | Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49 ISSN: 1091-6490 | Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors. |
| AID1345739 | Human leucine rich repeat kinase 2 (Leucine-rich repeat kinase (LRRK) family) | 2014 | Journal of medicinal chemistry, Feb-13, Volume: 57, Issue:3 ISSN: 1520-4804 | Discovery of highly potent, selective, and brain-penetrant aminopyrazole leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors. |
| Timeframe | Studies, This Drug (%) | All Drugs % |
|---|---|---|
| pre-1990 | 0 (0.00) | 18.7374 |
| 1990's | 0 (0.00) | 18.2507 |
| 2000's | 0 (0.00) | 29.6817 |
| 2010's | 3 (37.50) | 24.3611 |
| 2020's | 5 (62.50) | 2.80 |
| Publication Type | This drug (%) | All Drugs (%) |
|---|---|---|
| Trials | 0 (0.00%) | 5.53% |
| Reviews | 1 (12.50%) | 6.00% |
| Case Studies | 0 (0.00%) | 4.05% |
| Observational | 0 (0.00%) | 0.25% |
| Other | 7 (87.50%) | 84.16% |
| Condition | Indicated | Studies | First Year | Last Year | Average Age | Relationship Strength | Trials | pre-1990 | 1990's | 2000's | 2010's | post-2020 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Alcohol Drinking | 0 | 2020 | 2020 | 4.0 | high | 0 | 0 | 0 | 0 | 1 | 0 | |
| Congenital Zika Syndrome | 0 | 2020 | 2020 | 4.0 | high | 0 | 0 | 0 | 0 | 1 | 0 | |
| Disease Models, Animal | 0 | 2020 | 2020 | 4.0 | high | 0 | 0 | 0 | 0 | 1 | 0 | |
| Zika Virus Infection | 0 | 2020 | 2020 | 4.0 | high | 0 | 0 | 0 | 0 | 1 | 0 |
| Article | Year |
|---|---|
| A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein. Molecular pharmacology, , Volume: 96, Issue:5 | 2019 |