| Identification | Back Directory | [Name]
NVP-LCQ195 | [CAS]
902156-99-4 | [Synonyms]
AT 9311
AT-9311
LCQ 195
LCQ-195
NVP-LCQ195
NVP-LCQ195 (AT9311
NVP-LCQ195 (AT9311; LCQ195)
NVP-LCQ195;LCQ-195;AT-9311;NVP LCQ195
LCQ-195;AT-9311;NVP LCQ195;LCQ 195;AT9311;AT 9311
4-(2,6-Dichlorobenzamido)-N-(1-(methylsulfonyl)piperidin-4-yl)-1H-pyrazole-3-carboxamide
1H-Pyrazole-3-carboxamide, 4-[(2,6-dichlorobenzoyl)amino]-N-[1-(methylsulfonyl)-4-piperidinyl]-
4-(2,6-Dichlorobenzoylamino)-1H-pyrazole-3-carboxylic acid N-[1-(methylsulfonyl)piperidin-4-yl]amide
4-(2,6-dichloro-benzoylamino)-1H-pyrazole-3-carboxylic acid (1-methanesulphonyl-piperidin-4-yl)-amide | [Molecular Formula]
C17H19Cl2N5O4S | [MDL Number]
MFCD12031595 | [MOL File]
902156-99-4.mol | [Molecular Weight]
460.33 |
| Chemical Properties | Back Directory | [density ]
1.57±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
insoluble in H2O; ≥152.4 mg/mL in DMSO; ≥3.28 mg/mL in EtOH with gentle warming and ultrasonic | [form ]
solid | [pka]
11.10±0.70(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Uses]
NVP-LCQ195 (AT9311; LCQ195) is a small molecule heterocyclic inhibitor of CDK1, CDK2, CDK3 and CDK5 with IC50 of 1-42 nM.
IC50 Value: 1 nM(CDK5/p25 and CDK5/p35); 2 nM(CDK1/cyclinB and CDK2/cyclinA); 5 nM(CDK2/cyclinE); 42 nM(CDK3/cyclinE)
Target: CDKs
LCQ195 induced cell cycle arrest and eventual apoptotic cell death of MM cells, even at sub-lmol/l concentrations, spared non-malignant cells, and overcame the protection conferred to MM cells by stroma or cytokines of the bone marrow milieu. In MM cells, LCQ195 triggered decreased amplitude of transcriptional signatures associated with oncogenesis, drug resistance and stem cell renewal, including signatures of activation of key transcription factors for MM cells e.g. myc, HIF-1a, IRF4. Bortezomib-treated MM patients whose tumours had high baseline expression of genes suppressed by
LCQ195 had significantly shorter progression-free and overall survival than those with low levels of these transcripts in their MM cells. These observations provide insight into the biological relevance of multi-targeted CDK inhibition in MM. | [IC 50]
Cdk5/p25: 1 nM (IC50); CDK5/p35: 1 nM (IC50); Cdk1/cyclin B: 2 nM (IC50); cdk2/cyclin A: 2 nM (IC50); CDK2/cyclinE: 5 nM (IC50); CDK9/cyclinT1: 15 nM (IC50); CDK3/Cyclin E: 42 nM (IC50); cdk6/cyclin D3: 187 nM (IC50); CDK7/Cyclin H/MAT1: 3564 nM (IC50) | [storage]
Store at -20°C | [References]
[1] McMillin DW, Delmore J, Negri J et al. Molecular and cellular effects of multi-targeted cyclin-dependent kinase inhibition in myeloma: biological and clinical implications. Br J Haematol. 2011 Feb;152(4):420-32. DOI:10.1111/j.1365-2141.2010.08427.x |
|
| Company Name: |
SPIRO PHARMA
|
| Tel: |
|
| Website: |
www.spiropharma.com.cn |
|