WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H562115
CAS#: 1936529-65-5
Description: YKL-05-099 is a selective inhibitor of Salt-Inducible Kinase (SIK).
Hodoodo Cat#: H562115
Name: YKL-05-099
CAS#: 1936529-65-5
Chemical Formula: C32H34ClN7O3
Exact Mass: 599.24
Molecular Weight: 600.120
Elemental Analysis: C, 64.05; H, 5.71; Cl, 5.91; N, 16.34; O, 8.00
Synonym: YKL-05-099; YKL 05 099; YKL05099;
IUPAC/Chemical Name: 3-(2-Chloro-6-methylphenyl)-7-((2-methoxy-4-(1-methylpiperidin-4-yl)phenyl)amino)-1-(5-methoxypyridin-2-yl)-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one
InChi Key: VQINULODWGEVBB-UHFFFAOYSA-N
InChi Code: InChI=1S/C32H34ClN7O3/c1-20-6-5-7-25(33)29(20)39-19-23-17-35-31(37-30(23)40(32(39)41)28-11-9-24(42-3)18-34-28)36-26-10-8-22(16-27(26)43-4)21-12-14-38(2)15-13-21/h5-11,16-18,21H,12-15,19H2,1-4H3,(H,35,36,37)
SMILES Code: O=C1N(C2=NC=C(OC)C=C2)C3=NC(NC4=CC=C(C5CCN(C)CC5)C=C4OC)=NC=C3CN1C6=C(C)C=CC=C6Cl
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info:
Biological target: | Selective inhibitor of Salt-Inducible Kinase (SIK). |
In vitro activity: | Genetic targeting of SIK3 or MEF2C selectively suppressed the growth of transformed hematopoietic cells under in vitro and in vivo conditions. Similar phenotypes were obtained when cells were exposed to YKL-05-099, which caused cell-cycle arrest and apoptosis in MEF2C-expressing AML cell lines. An epigenomic analysis revealed that YKL-05-099 rapidly suppressed MEF2C function by altering the phosphorylation state and nuclear localization of HDAC4. Using a gatekeeper allele of SIK3, we found that the antiproliferative effects of YKL-05-099 occurred through on-target inhibition of SIK3 kinase activity. Based on these findings, 2 different mouse models were treated of MLL-AF9 AML with YKL-05-099, which attenuated disease progression in vivo and extended animal survival at well-tolerated doses. These findings validate SIK3 as a therapeutic target in MEF2C-addicted AML and provide a rationale for developing druglike inhibitors of SIK3 for definitive preclinical investigation and for studies in human patients. Reference: Tarumoto Y, Lin S, Wang J, Milazzo JP, Xu Y, Lu B, Yang Z, Wei Y, Polyanskaya S, Wunderlich M, Gray NS, Stegmaier K, Vakoc CR. Salt-inducible kinase inhibition suppresses acute myeloid leukemia progression in vivo. Blood. 2020 Jan 2;135(1):56-70. doi: 10.1182/blood.2019001576. PMID: 31697837; PMCID: PMC6940199. |
In vivo activity: | Genetic targeting of SIK3 or MEF2C selectively suppressed the growth of transformed hematopoietic cells under in vitro and in vivo conditions. Similar phenotypes were obtained when cells were exposed to YKL-05-099, which caused cell-cycle arrest and apoptosis in MEF2C-expressing AML cell lines. An epigenomic analysis revealed that YKL-05-099 rapidly suppressed MEF2C function by altering the phosphorylation state and nuclear localization of HDAC4. Using a gatekeeper allele of SIK3, we found that the antiproliferative effects of YKL-05-099 occurred through on-target inhibition of SIK3 kinase activity. Based on these findings, 2 different mouse models were treated of MLL-AF9 AML with YKL-05-099, which attenuated disease progression in vivo and extended animal survival at well-tolerated doses. These findings validate SIK3 as a therapeutic target in MEF2C-addicted AML and provide a rationale for developing druglike inhibitors of SIK3 for definitive preclinical investigation and for studies in human patients. Reference: Tarumoto Y, Lin S, Wang J, Milazzo JP, Xu Y, Lu B, Yang Z, Wei Y, Polyanskaya S, Wunderlich M, Gray NS, Stegmaier K, Vakoc CR. Salt-inducible kinase inhibition suppresses acute myeloid leukemia progression in vivo. Blood. 2020 Jan 2;135(1):56-70. doi: 10.1182/blood.2019001576. PMID: 31697837; PMCID: PMC6940199. |
Solvent | Max Conc. mg/mL | Max Conc. mM | |
---|---|---|---|
Solubility | |||
Soluble in DMSO | 103.3 | 172.18 |
The following data is based on the product molecular weight 600.12 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
---|---|---|---|
1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
Formulation protocol: | Tarumoto Y, Lin S, Wang J, Milazzo JP, Xu Y, Lu B, Yang Z, Wei Y, Polyanskaya S, Wunderlich M, Gray NS, Stegmaier K, Vakoc CR. Salt-inducible kinase inhibition suppresses acute myeloid leukemia progression in vivo. Blood. 2020 Jan 2;135(1):56-70. doi: 10.1182/blood.2019001576. PMID: 31697837; PMCID: PMC6940199. |
In vitro protocol: | Tarumoto Y, Lin S, Wang J, Milazzo JP, Xu Y, Lu B, Yang Z, Wei Y, Polyanskaya S, Wunderlich M, Gray NS, Stegmaier K, Vakoc CR. Salt-inducible kinase inhibition suppresses acute myeloid leukemia progression in vivo. Blood. 2020 Jan 2;135(1):56-70. doi: 10.1182/blood.2019001576. PMID: 31697837; PMCID: PMC6940199. |
In vivo protocol: | Tarumoto Y, Lin S, Wang J, Milazzo JP, Xu Y, Lu B, Yang Z, Wei Y, Polyanskaya S, Wunderlich M, Gray NS, Stegmaier K, Vakoc CR. Salt-inducible kinase inhibition suppresses acute myeloid leukemia progression in vivo. Blood. 2020 Jan 2;135(1):56-70. doi: 10.1182/blood.2019001576. PMID: 31697837; PMCID: PMC6940199. |
1: Wein MN, Liang Y, Goransson O, Sundberg TB, Wang J, Williams EA, O'Meara MJ, Govea N, Beqo B, Nishimori S, Nagano K, Brooks DJ, Martins JS, Corbin B, Anselmo A, Sadreyev R, Wu JY, Sakamoto K, Foretz M, Xavier RJ, Baron R, Bouxsein ML, Gardella TJ, Divieti-Pajevic P, Gray NS, Kronenberg HM. SIKs control osteocyte responses to parathyroid hormone. Nat Commun. 2016 Oct 19;7:13176. doi: 10.1038/ncomms13176. PubMed PMID: 27759007; PubMed Central PMCID: PMC5075806.
2: Sundberg TB, Liang Y, Wu H, Choi HG, Kim ND, Sim T, Johannessen L, Petrone A, Khor B, Graham DB, Latorre IJ, Phillips AJ, Schreiber SL, Perez J, Shamji AF, Gray NS, Xavier RJ. Development of Chemical Probes for Investigation of Salt-Inducible Kinase Function in Vivo. ACS Chem Biol. 2016 Aug 19;11(8):2105-11. doi: 10.1021/acschembio.6b00217. Epub 2016 Jun 6. PubMed PMID: 27224444; PubMed Central PMCID: PMC4992440.