NVP-2

Protein target name:

CDK9

Mechanism of action:

Inhibitor, ATP competitive

Recommended Concentration for use in cells:

250 to 1000 nM

Probe Availability

MedChemExpress

TOCRIS

Selleck Chemicals

Probe Information

Target and Probe Information

Target Details

Target class:

Protein kinase

Subclass:

CMGC

HUGO ID:

HGNC:1780

Entrez gene ID:

1025

UNIPROT ID:

P50750

Target alias:

C-2k, CDC2L4, CTK1, PITALRE, TAK

Probe Details

Chemical Probes Portal ID:

CPP137

Probe alias:

cpd 310

PubChem CID:

66937006

ChEMBL ID:

CHEMBL3656841

SMILES string:

ClC1=CN=C(N[C@H]2CC[C@H](N[C@H](C)COC)CC2)C=C1C3=CC=CC(NCC4(C#N)CCOCC4)=N3

InChi Key:

XWQVQSXLXAXOPJ-QNGMFEMESA-N

Orthogonal probe:

THAL-SNS-032

Physico-chemical properties

NMR:

1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.04 (d, J=6.26 Hz, 2H) 1.12-1.37 (m, 3H) 1.84-2.06 (m, 3H) 2.10-2.25 (m, 2H) 2.44-2.69 (m, 1H) 2.91-3.11 (m, 1H) 3.20-3.39 (m, 3H) 3.43-3.60 (m, 1H) 3.61-3.83 (m, 3H) 3.90-4.08 (m, 2H) 4.41 (d, J=8.22 Hz, 1H) 4.67-4.93 (m, 1H) 6.37-6.62 (m, 2H) 6.97 (d, J=7.43 Hz, 1H) 7.26 (s, 1H) 7.39-7.58 (m, 1H).

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

IC50

0.514 nM

Potency assay:

Cdk9/CyclinT1 IMAP

Off target activity

Probe Selectivity in Vitro:

Exhibits selectivity for CDK9 over a panel of 468 kinases, but inhibits DYRK1B (IC50 = 350 nM), displays <90% binding to CDK7 (IC50 >10 μM) and CDK13. Shows inhibition of CDK1/CycB, CDK2/CycA and CDK16/CycY kinases with IC50 values of 584 nM, 706 nM, and 605 nM

In cell validation

On target activity in cells

Potency in cells:

IC50

9 nM, 92-574 nM

Potency assay (cells):

Cell Apoptosis, anti-proliferation of leukemia cells

Target engagement assay (cells):

NVP-2 (250 nM-1 μM; 6 hours) engages CDK9 in wild-type and CRBN−/− MOLT4 cells at all concentrations, while CDK2 and CDK7 are unaffected

Primary Reference

Reference (doi):

10.1038/nchembio.2538

Reference (PMID):

29251720

NVP-2

Probe Availability

Probe Information

Target Details

C-2k, CDC2L4, CTK1, PITALRE, TAK

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

Primary Reference

Supporting Organizations

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NVP-2

Probe Availability

Probe Information

Target Details

C-2k, CDC2L4, CTK1, PITALRE, TAK

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

Primary Reference

Supporting Organizations

Interested in supporting the portal?