YKL-05-099

YKL-05-099
法律规范状态
法律规范	研究性新药（英语：Investigational New Drug）;
识别信息
	IUPAC命名法 3-(2-chloro-6-methylphenyl)-7-[2-methoxy-4-(1-methylpiperidin-4-yl)anilino]-1-(5-methoxypyridin-2-yl)-4H-pyrimido[4,5-d]pyrimidin-2-one; ;
CAS号	1936529-65-5
PubChem CID	121596782;
ChemSpider	60598522;
ChEMBL	ChEMBL5209511;
化学信息
化学式	C32H34ClN7O3
摩尔质量	600.12 g·mol−1
3D模型（JSmol（英语：JSmol））	交互式图像;
	SMILES CC1=C(C(=CC=C1)Cl)N2CC3=CN=C(N=C3N(C2=O)C4=NC=C(C=C4)OC)NC5=C(C=C(C=C5)C6CCN(CC6)C)OC;
	InChI 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); Key:VQINULODWGEVBB-UHFFFAOYSA-N;

YKL-05-099是一种用作盐诱导激酶（英语：Salt-inducible kinase）（SIK）抑制剂的试验药物（英语：Experimental drug）。它具有抗炎作用，用于研究盐诱导激酶抑制剂在治疗白血病、骨质疏松症和肥胖症等多种疾病方面的潜在应用。^[1]^[2]^[3]^[4]^[5]^[6]^[7]

参考来源

^ 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 Chemical Biology. 2016-08, 11 (8): 2105–2111. PMC 4992440 . PMID 27224444. doi:10.1021/acschembio.6b00217.
^ 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. Nature Communications. 2016-10, 7: 13176. Bibcode:2016NatCo...713176W. PMC 5075806 . PMID 27759007. doi:10.1038/ncomms13176.
^ 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. 2020-01, 135 (1): 56–70. PMC 6940199 . PMID 31697837. doi:10.1182/blood.2019001576.
^ Tang CC, Castro Andrade CD, O'Meara MJ, Yoon SH, Sato T, Brooks DJ, Bouxsein ML, Martins JD, Wang J, Gray NS, Misof B, Roschger P, Blouin S, Klaushofer K, Velduis-Vlug A, Vegting Y, Rosen CJ, O'Connell D, Sundberg TB, Xavier RJ, Ung P, Schlessinger A, Kronenberg HM, Berdeaux R, Foretz M, Wein MN. Dual targeting of salt inducible kinases and CSF1R uncouples bone formation and bone resorption. eLife. 2021-06, 10. PMC 8238509 . PMID 34160349. doi:10.7554/eLife.67772 .
^ Canté-Barrett K, Meijer MT, Cordo' V, Hagelaar R, Yang W, Yu J, Smits WK, Nulle ME, Jansen JP, Pieters R, Yang JJ, Haigh JJ, Goossens S, Meijerink JP. MEF2C opposes Notch in lymphoid lineage decision and drives leukemia in the thymus. JCI Insight. 2022-07-08;7(13):e150363. doi:10.1172/jci.insight.150363 PMID 35536646
^ Shi F, de Fatima Silva F, Liu D, Patel HU, Xu J, Zhang W, Türk C, Krüger M, Collins S. Salt-inducible kinase inhibition promotes the adipocyte thermogenic program and adipose tissue browning. Molecular Metabolism. 2023-08, 74: 101753. PMC 10319839 . PMID 37321371. doi:10.1016/j.molmet.2023.101753.
^ Momenzadeh K, Yeritsyan D, Abbasian M, Kheir N, Hanna P, Wang J, Dosta P, Papaioannou G, Goldfarb S, Tang CC, Amar-Lewis E, Nicole Prado Larrea M, Martinez Lozano E, Yousef M, Wixted J, Wein M, Artzi N, Nazarian A. Stimulation of fracture mineralization by salt-inducible kinase inhibitors. Frontiers in Bioengineering and Biotechnology. 2024, 12: 1450611. PMC 11445660 . PMID 39359266. doi:10.3389/fbioe.2024.1450611 .

[1] 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 Chemical Biology. 2016-08, 11 (8): 2105–2111. PMC 4992440 . PMID 27224444. doi:10.1021/acschembio.6b00217.

[2] 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. Nature Communications. 2016-10, 7: 13176. Bibcode:2016NatCo...713176W. PMC 5075806 . PMID 27759007. doi:10.1038/ncomms13176.

[3] 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. 2020-01, 135 (1): 56–70. PMC 6940199 . PMID 31697837. doi:10.1182/blood.2019001576.

[4] Tang CC, Castro Andrade CD, O'Meara MJ, Yoon SH, Sato T, Brooks DJ, Bouxsein ML, Martins JD, Wang J, Gray NS, Misof B, Roschger P, Blouin S, Klaushofer K, Velduis-Vlug A, Vegting Y, Rosen CJ, O'Connell D, Sundberg TB, Xavier RJ, Ung P, Schlessinger A, Kronenberg HM, Berdeaux R, Foretz M, Wein MN. Dual targeting of salt inducible kinases and CSF1R uncouples bone formation and bone resorption. eLife. 2021-06, 10. PMC 8238509 . PMID 34160349. doi:10.7554/eLife.67772 .

[5] Canté-Barrett K, Meijer MT, Cordo' V, Hagelaar R, Yang W, Yu J, Smits WK, Nulle ME, Jansen JP, Pieters R, Yang JJ, Haigh JJ, Goossens S, Meijerink JP. MEF2C opposes Notch in lymphoid lineage decision and drives leukemia in the thymus. JCI Insight. 2022-07-08;7(13):e150363. doi:10.1172/jci.insight.150363 PMID 35536646

[6] Shi F, de Fatima Silva F, Liu D, Patel HU, Xu J, Zhang W, Türk C, Krüger M, Collins S. Salt-inducible kinase inhibition promotes the adipocyte thermogenic program and adipose tissue browning. Molecular Metabolism. 2023-08, 74: 101753. PMC 10319839 . PMID 37321371. doi:10.1016/j.molmet.2023.101753.

[7] Momenzadeh K, Yeritsyan D, Abbasian M, Kheir N, Hanna P, Wang J, Dosta P, Papaioannou G, Goldfarb S, Tang CC, Amar-Lewis E, Nicole Prado Larrea M, Martinez Lozano E, Yousef M, Wixted J, Wein M, Artzi N, Nazarian A. Stimulation of fracture mineralization by salt-inducible kinase inhibitors. Frontiers in Bioengineering and Biotechnology. 2024, 12: 1450611. PMC 11445660 . PMID 39359266. doi:10.3389/fbioe.2024.1450611 .

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