HG-10-102-01LRRK2 inhibitor CAS# 1351758-81-0 |
Quality Control & MSDS
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| Cas No. | 1351758-81-0 | SDF | Download SDF |
| PubChem ID | 58539301 | Appearance | Powder |
| Formula | C17H20ClN5O3 | M.Wt | 377.83 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Synonyms | LRRK2 inhibitor 1 | ||
| Solubility | DMSO : ≥ 50 mg/mL (132.33 mM) *"≥" means soluble, but saturation unknown. | ||
| Chemical Name | [4-[[5-chloro-4-(methylamino)pyrimidin-2-yl]amino]-3-methoxyphenyl]-morpholin-4-ylmethanone | ||
| SMILES | CNC1=NC(=NC=C1Cl)NC2=C(C=C(C=C2)C(=O)N3CCOCC3)OC | ||
| Standard InChIKey | YEVOZZZLKJKCCD-UHFFFAOYSA-N | ||
| Standard InChI | InChI=1S/C17H20ClN5O3/c1-19-15-12(18)10-20-17(22-15)21-13-4-3-11(9-14(13)25-2)16(24)23-5-7-26-8-6-23/h3-4,9-10H,5-8H2,1-2H3,(H2,19,20,21,22) | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| Description | HG-10-102-01 is a potent and selective inhibitor of wild-type LRRK2(IC50=23.3 nM) and the G2019S mutant(IC50=3.2 nM)
IC50 Value: 23.3 nM (WT LRRK2); 3.2 nM (LRRK2 G2019S) [1]
Target: LRRK2
HG-10-102-01 maintains the ability to potently inhibit the biochemical activity of wild-type and G2019S mutant LRRK2. HG-10-102-01 exhibited biochemical IC50s of 20.3 and 3.2 nM against wild-type LRRK2 and LRRK2[G2019S], respectively. At a concentration of 10 μM, HG-10-102-01 only inhibited the kinase activities of MLK1 and MNK2 to greater than 80% of the DMSO control. Dose-response analysis revealed inhibition of MLK1 with an IC50 2.1 μM and MNK2 with an IC50 0.6 μM. KinomeScan analysis against a near comprehensive panel of 451 kinases at a concentration of 1 μM resulted in no interactions detected with kinases other than G2019S LRRK2 with the exception of one mutant form of c-Kit (L576P) demonstrating the outstanding selectivity of this inhibitor.
HG-10-102-01 significantly inhibited phosphorylation of wildtype LRRK2 and LRRK2[G2019S] mutant at Ser910 and Ser935 at 0.3-1.0 μM in cell culture, which is approximately the same potency as LRRK2-IN-1 (1). HG-10-102-01 is relatively insensitive to the A2016T mutation which suggests that this mutant will not be useful to validate whether the pharmacological effects of the compound are LRRK2-dependent.
HG-10-102-01 can inhibit phosphorylation of Ser910 and Ser935 of LRRK2 in brain and peripheral tissues following intraperitoneal doses of 50 mg/kg. Further optimization of this chemo-type especially in regards to in vivo half-life will be reported in due course [1]. References: | |||||
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HG-10-102-01 is a potent and selective inhibitor of leucine-rich repeat kinase 2 (LRRK2) with the IC50 values of 20.3nM and 3.2nM for wild type LRRK2 and LRRK2 [G1019S], respectively [1].
HG-10-102-01 has shown the potent and selective inhibitor of LRRK2 with the IC50 values of 20.3nM, 153.7nM, 95.9nM and 3.2nM for wild type LRRK2, LRRK2 [A2016T], LRRK2 [G2019S+A1016T] and LRRK2 [G1019S], respectively. In addition, HG-10-102-01 has been reported to induced a dose-dependent inhibition of Ser910 and Ser935 phosphorylation in both wild-type LRRK2 and LRRK2 [G2019S] stably transfected into HEK 293 cells. Moreover, it has been demonstrated that increasing doses of HG-10-102-01 led to similar dephosphorylation of endogenous LRRK2 at Ser910 and Ser935 in HEK293 cells, mouse Swiss 3T3 cells and mouse embryonic fibroblast cells [1].
References:
[1] Choi HG1, Zhang J, Deng X, Hatcher JM, Patricelli MP, Zhao Z, Alessi DR, Gray NS. Brain Penetrant LRRK2 Inhibitor. ACS Med Chem Lett. 2012 Aug 9;3(8):658-662. Epub 2012 Jun 18.
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Synthesis of [(11)C]HG-10-102-01 as a new potential PET agent for imaging of LRRK2 enzyme in Parkinson's disease.[Pubmed:28223019]
Bioorg Med Chem Lett. 2017 Mar 15;27(6):1351-1355.
The reference standard (4-((5-chloro-4-(methylamino)pyrimidin-2-yl)amino)-3-methoxyphenyl)(morpholino)me thanone (HG-10-102-01) and its precursor (4-((5-chloro-4-(methylamino)pyrimidin-2-yl)amino)-3-hydroxyphenyl)(morpholino)me thanone (desmethyl-HG-10-102-01) were synthesized from 2,4,5-trichloropyrimide and 3-methoxy-4-nitrobenzoic acid with overall chemical yield 49% in four steps and 14% in five steps, respectively. The target tracer (4-((5-chloro-4-(methylamino)pyrimidin-2-yl)amino)-3-[(11)C]methoxyphenyl)(morpho lino)methanone ([(11)C]HG-10-102-01) was prepared from the precursor desmethyl-HG-10-102-01 with [(11)C]CH3OTf through O-[(11)C]methylation and isolated by HPLC combined with SPE in 45-55% radiochemical yield, based on [(11)C]CO2 and decay corrected to end of bombardment (EOB). The radiochemical purity was >99%, and the specific activity (SA) at EOB was 370-1110GBq/mumol with a total synthesis time of approximately 40-min from EOB.
