| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| Other Sizes |
|
Purity: ≥98%
INCB054329 is a novel potent and selective inhibitor of Bromodomain and extra-terminal (BET) protein. It that targets Bromodomains 1 (BD1) and BD2 of BRD2, BRD3 and BRD4. INCB054329 inhibited binding of BRD2, BRD3 and BRD4 to an acetylated histone H4 peptide with low nanomolar potency. In myeloma cell lines, treatment with INCB054329 inhibited expression of c-MYC and induced HEXIM1. The majority of myeloma, AML, and lymphoma cell lines tested were growth inhibited by INCB054329 with potencies less than 200 nM. Selectivity was seen when compared with nontransformed cells as the potency for growth inhibition of IL-2 stimulated T-cells from normal donors was greater than 1300 nM. Cell cycle analysis revealed treatment-induced G1 arrest. Furthermore in both AML and lymphoma cell lines, INCB054329 induced apoptosis consistent with increased expression of pro-apoptotic regulators. In vivo, oral administration of INCB054329 inhibited tumor growth in several models of hematologic cancers. In the MM1.S multiple myeloma xenograft model, inhibition of tumor growth was correlated with reduction of c-MYC levels. PK-PD analysis showed c-MYC suppression was associated with an IC50 value of less than 100 nM in vivo. In summary these studies demonstrate that INCB054329 is a potent inhibitor of BET transcriptional regulators in models of hematologic malignancies in vitro and in vivo and support its clinical development for the treatment of cancer.
| ln Vitro |
INCB054329 is a bromodomain and extra-terminal motif (BET) inhibitor[1]. INCB054329 inhibits binding of BRD2, BRD3 and BRD4 to an acetylated histone H4 peptide with low nanomolar efficacy. In myeloma cell lines, treatment with INCB054329 inhibited expression of c- MYC and activated HEXIM1. The majority of myeloma, AML, and lymphoma cell lines studied are growth suppressed by INCB054329 with potencies less than 200 nM. Selectivity is demonstrated when compared with nontransformed cells since the potency for growth inhibition of IL-2 activated T- cells from normal donors is greater than 1300 nM. Cell cycle analysis demonstrates treatment-induced G1 arrest. Furthermore in both AML and lymphoma cell lines, INCB054329 promotes apoptosis commensurate with elevated expression of pro-apoptotic regulators[2].
|
||
|---|---|---|---|
| ln Vivo |
In a number of hematologic cancer models, oral treatment of INCB054329 reduces the growth of tumors. Reduction of c-MYC levels is linked with prevention of tumor growth in the MM1.S multiple myeloma xenograft model. According to PK-PD study, in vivo c-MYC suppression is linked to an IC50 value of less than 100 nM[2].
|
||
| Animal Protocol |
|
||
| References |
[1]. Pérez-Salvia M, et al. Bromodomain inhibitors and cancer therapy: From structures to applications. Epigenetics. 2017 May 4;12(5):323-339.
[2]. Phillip CC Liu, et al. Abstract 3523: Discovery of a novel BET inhibitor INCB054329. |
| Molecular Formula |
C19H16N4O3
|
|---|---|
| Molecular Weight |
348.3553
|
| CAS # |
1628607-64-6
|
| Related CAS # |
(R)-INCB054329;1628607-63-5;INCB054329 Racemate;1628607-62-4
|
| Appearance |
Typically exists as solids (or liquids in special cases) at room temperature
|
| SMILES |
O1C2=C(C3C(C)=NOC=3C)C=CC3=C2N(C(N3)=O)[C@@]([H])(C2=CC=CC=N2)C1
|
| Synonyms |
INCB54329; INCB 54329; INCB-54329; INCB054329; INCB-054329; INCB 054329
|
| 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) |
|
|||
|---|---|---|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.18 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 (7.18 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 (7.18 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 | 2.8706 mL | 14.3530 mL | 28.7059 mL | |
| 5 mM | 0.5741 mL | 2.8706 mL | 5.7412 mL | |
| 10 mM | 0.2871 mL | 1.4353 mL | 2.8706 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.
 Overview of bromodomain inhibition. Bromodomains recognize acetylation marks in histone tails and recruit transcriptional machinery promoting target gene transcription, such as in the case ofc-MYC. Bromodomain inhibitors prevent interaction between the bromodomain and the acetyl group, causing the downregulation of certain genes. Bromodomains play a key role in gene transcription regulation.Epigenetics. 2017; 12(5): 323–339. |
|---|
 Structure-based phylogeny of the human bromodomains and their inhibitors. There are 61 bromodomains in 46 bromodomain-containing proteins. Roman numerals indicate the eight major structural classes.Epigenetics. 2017; 12(5): 323–339. |
 BET bromodomain inhibitor molecules. Non-BET bromodomain inhibitor molecules.Epigenetics. 2017; 12(5): 323–339. |
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA
