| Chemical Properties | Back Directory | [Boiling point ]
518.5±50.0 °C(Predicted) | [density ]
1.30±0.1 g/cm3(Predicted) | [storage temp. ]
-20°C | [solubility ]
H2O: 15 mg/mL, clear | [form ]
powder | [pka]
8.10±0.50(Predicted) | [color ]
white to beige | [Water Solubility ]
H2O: 15mg/mL, clear | [InChI]
1S/C18H22N6O.ClH/c1-3-14(19)10-21-17-6-7-20-18(23-17)15-8-12(4-5-16(15)25)13-9-22-24(2)11-13;/h4-9,11,14,25H,3,10,19H2,1-2H3,(H,20,21,23);1H/t14-;/m1./s1 | [InChIKey]
NBKRZGHHBBHLOQ-PFEQFJNWSA-N | [SMILES]
Cl.[n]1(ncc(c1)c2cc(c(cc2)O)c3nc(ccn3)NC[C@H](N)CC)C |
| Hazard Information | Back Directory | [Uses]
CRT0066101 is a potent and orally active PKD inhibitor with IC50 values of 1 nM, 2.5 nM and 2 nM for PKD1, PKD2, and PKD3, respectively[1]. CRT0066101 is also a potent PIM2 inhibitor with an IC50 of ~135.7?nM. CRT0066101 exhibits anti-inflammatory activity in mice LPS (HY-D1056)-induced lung injury models, and has anticancer effects[1][2][3]. | [Biochem/physiol Actions]
CRT0066101 is a very potent inhibitor of Protein Kinase D (PKD) isoforms with IC50 values for PKD-1, -2 and -3 = 1, 2.5 and 2 nM, respecitively. CRT0066101 has been shown to have anticancer activity. CRT0066101 potently inhibits proliferation of PANC-1 pancreatic cells, and blocks migration and invasion of U87MG glioblastoma cells. CRT0066101 has also been shown to decrease growth of primary tumors and metastasis of ER(-) breast cancers. | [in vivo]
CRT0066101 (80 mg/kg/day; oral gavage; once daily; for 21 days) in Panc-1 orthotopic model potently blocks tumor growth in vivo[1].
CRT0066101 (10 mg/kg, i.p., every two days for 3 times) exhibits a protective effect against LPS-induced pneumonia and alleviates lung damage in C57BL/6J mice[3]. | Animal Model: | CR-UK nu/nu mice injected with Panc-1 cells[1] | | Dosage: | 80 mg/kg/day | | Administration: | Oral gavage; once daily; for 21 days | | Result: | Potently blocked tumor growth in vivo. |
| Animal Model: | LPS (HY-D1056)-induced lung injury in C57BL/6J mice[3] | | Dosage: | 10 mg/kg | | Administration: | i.p., once every two days for 3 times | | Result: | Inhibited the expression of MyD88 and TLR4, inhibited the phosphorylation of NF-κB, ERK and JNK. |
| [IC 50]
PKD1: 1 nM (IC50); PKD2: 2.5 nM (IC50); PKD3: 2 nM (IC50); PIM2: 135.7 nM (IC50) | [References]
[1] Harikumar KB, et al. A novel small-molecule inhibitor of protein kinase D blocks pancreatic cancer growth in vitro and in vivo. Mol Cancer Ther. 2010 May;9(5):1136-46. DOI:10.1158/1535-7163.MCT-09-1145
[2] Xi Chen, et al. Identification and assessment of new PIM2 inhibitors for treating hematologic cancers: A combined approach of energy-based virtual screening and machine learning evaluation. Arch Pharm (Weinheim). 2024 Jan 23:e2300516. DOI:10.1002/ardp.202300516
[3] Cui B, et al., Small molecule inhibitor CRT0066101 inhibits cytokine storm syndrome in a mouse model of lung injury. Int Immunopharmacol. 2023 Jul;120:110240. DOI:10.1016/j.intimp.2023.110240 |
|
| Company Name: |
Sigma-Aldrich
|
| Tel: |
021-61415566 800-8193336 |
| Website: |
https://www.sigmaaldrich.cn |
| Company Name: |
SPIRO PHARMA
|
| Tel: |
|
| Website: |
www.spiropharma.com.cn |
| Company Name: |
Merck KGaA
|
| Tel: |
21-20338288 |
| Website: |
www.sigmaaldrich.cn |
|