Delving into the Latest Updates on NVP-LCQ195 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

+ [2]

Target

CDK1 x CDK2 x CDK3 x CDK5 x CDK9

Mechanism

CDK1 inhibitors(Cyclin-dependent kinase 1 inhibitors), CDK2 inhibitors(Cyclin-dependent kinase 2 inhibitors), CDK3 inhibitors(cyclin dependent kinase 3 inhibitors)

+ [2]

Therapeutic Areas

NeoplasmsImmune System DiseasesCardiovascular Diseases+ [1]

Active Indication-

Inactive Indication

Multiple Myeloma

Originator Organization

Astex Therapeutics Ltd.

Active Organization-

Inactive Organization

Novartis Pharmaceuticals Corp.

Harvard Medical School

Astex Therapeutics Ltd.

+ [1]

Drug Highest PhasePendingPreclinical

First Approval Date-

Regulation-

Structure

Molecular FormulaC17H19Cl2N5O4S

InChIKeyCCUXEBOOTMDSAM-UHFFFAOYSA-N

CAS Registry902156-99-4

SummaryCell 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.

100 Deals associated with NVP-LCQ195

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Multiple Myeloma	Preclinical	US	Novartis Pharmaceuticals Corp.	16 Nov 2007
Multiple Myeloma	Preclinical	US	Harvard Medical School	16 Nov 2007
Multiple Myeloma	Preclinical	US	Dana-Farber Cancer Institute, Inc.	16 Nov 2007
Multiple Myeloma	Preclinical	US	Astex Therapeutics Ltd.	16 Nov 2007