| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
CDK9 (potent and selective ATP-competitive inhibitor) [1]
|
|---|---|
| ln Vitro |
The KOPT-K1, Jurkat, P12-ICHIKAWA, DU.528, MOLT 16, HSB-2, PF-382, SKW-3, SUP-T11, DND-41, and HPB are inhibited by NVP-2, which also has an anti-leukemia cell proliferation effect. The IC50 values of ALL cells are 0.1688 μM, 0.1233 μM, 0.5736 μM, 0.1575 μM, 0.1620 μM, 0.1585 μM, 0.1808 μM, 0.2589μM, 0.0918μM, and 0.3023μM [1]. In both wild-type and CRBN/MOLT4 cells, NVP-2 (250 nM-1 μM; 6 hours) binds CDK9 at all doses, but CDK2 and CDK7 remain unaffected [1]. With an IC50 value of 9 nM, NVP-2 (0-10 nM; 72 hours) demonstrates CRBN-dependent anti-proliferative and pro-apoptotic actions in MOLT4 cells [1]. In MOLT4 cells, NVP-2 (250 nM; 24 hours) causes apoptosis and increases the expression of caspase-3 and γH2A.X. Nevertheless, compound elution considerably decreased the amount of apoptosis caused by NVP-2 [1].
Treatment of MOLT4 T-ALL cells with 250 nM NVP-2 for 6 hours resulted in transcriptional changes that correlated more closely with those induced by BET protein degradation (dBET6) than with BET bromodomain inhibition (JQ1). [1] The toxicity profile of NVP-2 across a panel of cancer cell lines closely matched that of the BET degrader dBET6 and, to a lesser extent, the CDK7/12/13 inhibitor THZ-1, but was dissimilar from the BET inhibitor JQ1. [1] Treatment with NVP-2 recapitulated the disproportional transcriptional impact on the core regulatory circuitry (CRC) genes observed with dBET6, while having no impact on the subcellular distribution of BRD4. [1] |
| Enzyme Assay |
CDK9/Cyclin T1 kinase inhibition assays were performed using a commercial, generic kinase activity assay based on a TR-FRET readout. Briefly, recombinant CDK9/Cyclin T1 enzyme was diluted in kinase buffer and incubated in a multi-well plate with varying concentrations of the test compound dissolved in DMSO. A substrate solution containing a peptide substrate and ATP was then added to initiate the reaction. After incubation, a detection mixture containing EDTA to stop the reaction, a europium-labeled anti-ADP antibody, and an Alexa Fluor 647-labeled ADP tracer was added. The ratio of fluorescence emission at 665 nm and 615 nm was measured to determine the level of ADP produced, which correlates with kinase activity. [1]
|
| Cell Assay |
Cell Viability Assay[1]
Cell Types: Leukemia Cell Line Tested Concentrations: 0.1233 µM-0.5736 µM Incubation Duration: 72 hrs (hours) Experimental Results: Inhibition of leukemia cell line viability. Western Blot Analysis[1] Cell Types: Wild-type and CRBN−/− MOLT4 Cell Tested Concentrations: 1 μM; 500 nM; 250 nM Incubation Duration: 6 hrs (hours) Experimental Results: Substoichiometric degradation of CDK9 at all concentrations. Apoptosis analysis [1] Cell Types: wild type and CRBN−/− MOLT4 Cell Tested Concentrations: 250 nM Incubation Duration: 24 hrs (hours) Experimental Results: Induction of apoptosis, washout compounds alleviated NVP-2-induced apoptosis. Cell proliferation assay[1] Cell Types: MOLT4 Cell Tested Concentrations: 0-10 nM Incubation Duration: 72 hrs (hours) Experimental Results: demonstrated anti-proliferative effect in MOLT4 cells. For transcriptomic analysis, MOLT4 cells were treated with 250 nM NVP-2 for 6 hours. Total RNA was then isolated using a commercial kit, and spike-in RNA controls were added during the isolation process for normalization. RNA-seq libraries were prepared and sequenced. Gene expression fold changes were calculated relative to DMSO-treated controls. [1] For toxicity profiling, a panel of cancer cell lines was treated with NVP-2 across a range of concentrations for 72 hours. Cell viability was assessed by measuring cellular ATP levels using a luminescent cell viability assay. Dose-response curves were generated, and the area under the curve (AUC) was calculated to summarize the drug's effect. [1] |
| References | |
| Additional Infomation |
NVP-2 is a highly efficient and selective ATP-competitive cyclin-dependent kinase 9 (CDK9) probe. NVP-2 induces apoptosis.
NVP-2 was used as a tool compound to compare the transcriptional consequences of functional P-TEFb inhibition with BET inhibition and BET degradation. [1] This study found that transcriptional changes following BET degradation were more correlated with ATP-competitive P-TEFb inhibition (using NVP-2) than with BET bromodomain inhibition. [1] |
| Molecular Formula |
C27H37CLN6O2
|
|---|---|
| Molecular Weight |
513.0747
|
| Exact Mass |
512.266
|
| CAS # |
1263373-43-8
|
| PubChem CID |
66937006
|
| Appearance |
White to yellow solid powder
|
| Density |
1.2±0.1 g/cm3
|
| Boiling Point |
704.5±60.0 °C at 760 mmHg
|
| Flash Point |
379.9±32.9 °C
|
| Vapour Pressure |
0.0±2.2 mmHg at 25°C
|
| Index of Refraction |
1.594
|
| LogP |
3.28
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
8
|
| Rotatable Bond Count |
10
|
| Heavy Atom Count |
36
|
| Complexity |
706
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
C[C@H](COC)NC1CCC(CC1)NC2=NC=C(C(=C2)C3=NC(=CC=C3)NCC4(CCOCC4)C#N)Cl
|
| InChi Key |
XWQVQSXLXAXOPJ-NJDAHSKKSA-N
|
| InChi Code |
InChI=1S/C27H37ClN6O2/c1-19(16-35-2)32-20-6-8-21(9-7-20)33-26-14-22(23(28)15-30-26)24-4-3-5-25(34-24)31-18-27(17-29)10-12-36-13-11-27/h3-5,14-15,19-21,32H,6-13,16,18H2,1-2H3,(H,30,33)(H,31,34)/t19-,20-,21-/m1/s1
|
| Chemical Name |
4-({[6-(5-chloro-2-{[(1r,4r)-4-{[(2R)-1-methoxypropan-2-yl]amino}cyclohexyl]amino}pyridin-4-yl)pyridin-2-yl]amino}methyl)oxane-4-carbonitrile
|
| Synonyms |
NVP-2; NVP 2; NVP2.
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : ≥ 100 mg/mL (~194.91 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.87 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.87 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (4.87 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9491 mL | 9.7453 mL | 19.4905 mL | |
| 5 mM | 0.3898 mL | 1.9491 mL | 3.8981 mL | |
| 10 mM | 0.1949 mL | 0.9745 mL | 1.9491 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA