1936529-65-5
1936529-65-5 structure
- Name: YKL-05-099
- Chemical Name: YKL-05-099
- CAS Number: 1936529-65-5
- Molecular Formula: C32H34ClN7O3
- Molecular Weight: 600.110
- Catalog: Signaling Pathways Immunology/Inflammation Salt-inducible Kinase (SIK)
- Create Date: 2018-06-21 23:14:46
- Modify Date: 2024-01-18 14:34:03
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YKL-05-099 is a salt-inducible kinase (SIK) probe; inhibits SIK2 with an IC50 of 40 nM.
| Name | YKL-05-099 |
|---|---|
| Synonyms |
Pyrimido[4,5-d]pyrimidin-2(1H)-one, 3-(2-chloro-6-methylphenyl)-3,4-dihydro-7-[[2-methoxy-4-(1-methyl-4-piperidinyl)phenyl]amino]-1-(5-methoxy-2-pyridinyl)-
3-(2-Chloro-6-methylphenyl)-7-{[2-methoxy-4-(1-methyl-4-piperidinyl)phenyl]amino}-1-(5-methoxy-2-pyridinyl)-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one |
| Description | YKL-05-099 is a salt-inducible kinase (SIK) probe; inhibits SIK2 with an IC50 of 40 nM. |
|---|---|
| Related Catalog | |
| Target |
IC50: 40 nM (SIK2)[1] |
| In Vitro | YKL-05-099 has slightly less potent SIK2-inhibitory (IC50=40 nM) and IL-10-enhancing activities (EC50=460 nM). YKL-05-099 binds to SIK1 and SIK3 with IC50s of 10 and 30 nM, respectively, in a competitive binding assay. Preincubating bone marrow-derived macrophages with YKL-05-099 reduces LPS stimulated phosphorylation of HDAC5 at the SIK-specific phosphorylation site Ser259. YKL-05-099 suppresses production of the inflammatory cytokines TNFα, IL-6 and IL-12p40, and only modestly enhances IL-1β release in BMDCs stimulated with the yeast cell wall extract Zymosan A[1]. |
| In Vivo | YKL-05-099 is non-toxic at concentrations less than 10 μM and stable in mouse liver microsomes for more than 2 hours. YKL-05-099 is highly soluble (PBS solubility=428 μM) and present in an unbound state at appreciable levels in mouse plasma. YKL-05-099 dose dependently decreases phosphorylation of HDAC5 at the SIK-regulated site Ser259; reduced phosphorylation is observed at the lowest dose (5 mg/Kg) and is below the limit of detection by immunoblotting beginning at the 20 mg/Kg dose. YKL-05-099 dose-dependently reduces abundance of TNFα in serum beginning at 5 mg/Kg, and increases IL-10 levels at the 20 mg/Kg dose by more than 2-fold[1]. |
| Animal Admin | Mice: YKL-05-099 is diluted in 5% N-methyl-2-pyrrolidinone, 5% Solutol HS15 and 90% normal saline and administered IP to male 8–10 week-old C57BL/6 mice. Serum and tissue samples are collected after euthanizing mice by CO2 inhalation overdose followed by cervical dislocation[1]. |
| References |
| Density | 1.3±0.1 g/cm3 |
|---|---|
| Boiling Point | 761.0±70.0 °C at 760 mmHg |
| Molecular Formula | C32H34ClN7O3 |
| Molecular Weight | 600.110 |
| Flash Point | 414.1±35.7 °C |
| Exact Mass | 599.241150 |
| LogP | 3.12 |
| Vapour Pressure | 0.0±2.6 mmHg at 25°C |
| Index of Refraction | 1.647 |
| Storage condition | 2-8℃ |