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NVP-LCQ195

(CAS: 902156-99-4)

Suppliers of NVP-LCQ195

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AdooQ BioScience, LLC [email protected] 855-GO-ADOOQ (855-462-3667) (US & Canada Toll Free) 866-930-6790 (US & Canada Toll Free) +1-323-389-9269 (Outside of US & Canada) USA

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CHEMSCENE, LLC [email protected] 732-484-9848 USA

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MedChemexpress Co., Ltd. [email protected] 609-228-6898 USA

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Price and Availability: USD306/5mg () USD430/10mg ()
Quality Control & MSDS Files: HNMR LCMS MSDS

MedKoo Biosciences, Inc. [email protected] 919-279-0682 USA

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Shanghai Haoyuan Chemexpress Co., Ltd. [email protected] +86 (21) 5187-0955 / +86 (21) 5895-5995 China

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Background Information of NVP-LCQ195

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.

Solubility of NVP-LCQ195

Solubility Sources
DMSO MedChemexpress Co., Ltd.

Storage Condition of NVP-LCQ195

Storage Condition Sources

MSDS Information

MSDS Sources
MedChemexpress Co., Ltd.

Quality Control and Spectral Data

QC Reports Sources
[HNMR] [LCMS] MedChemexpress Co., Ltd.

Mechanism and Indications

Signaling Pathways Cell Cycle/DNA Damage
Target CDK
Research Area Cancer
Indications

Clinical Information

Product Name Sponsor & Collaborators Indications Start Date End Date Phase
NVP-LCQ195 - No Development Reported

Chemical Information

M.Wt Formula CAS No. Synonyms
460.33 C17H19Cl2N5O4S 902156-99-4 LCQ-195;AT-9311;NVP LCQ195;LCQ 195;AT9311;AT 9311; 4-(2,6-dichlorobenzamido)-N-(1-(methylsulfonyl)piperidin-4-yl)-1H-pyrazole-5-carboxamide

Structure Information of NVP-LCQ195

Smiles CS(=O)(N1CCC(NC(C2=C(NC(C3=C(Cl)C=CC=C3Cl)=O)C=NN2)=O)CC1)=O
InChI InChI=1S/C17H19Cl2N5O4S/c1-29(27,28)24-7-5-10(6-8-24)21-17(26)15-13(9-20-23-15)22-16(25)14-11(18)3-2-4-12(14)19/h2-4,9-10H,5-8H2,1H3,(H,20,23)(H,21,26)(H,22,25)

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Chemical and Physical Properties

Appearance:White to off-white solid Melting point:
Boiling point: Flash Point:
Water Solubility: Solubility:>152.4mg/mL in DMSO
Density: Merck:
BRN: Refractive Index:
Vapour: EINECS:
Optical Rotation: alpha:

Reference

[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.
Cell cycle regulators, such as cyclin-dependent kinases (CDKs), are appealing targets for multiple myeloma (MM) therapy given the increased proliferative rates of tumour cells in advanced versus early stages of MM. We hypothesized that a multi-targeted CDK inhibitor with a different spectrum of activity compared to existing CDK inhibitors could trigger distinct molecular sequelae with therapeutic implications for MM. We therefore studied the small molecule heterocyclic compound NVP-LCQ195/AT9311 (LCQ195), which inhibits CDK1, CDK2 and CDK5, as well as CDK3 and CDK9. LCQ195 induced cell cycle arrest and eventual apoptotic cell death of MM cells, even at sub-μmol/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-1α, 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.

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