| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg |
|
||
| Other Sizes |
|
Purity: ≥98%
BAY-1238097 (the S-isomer of BAY-1238097) is a novel, potent and selective inhibitor of BET (bromodomain and extra-terminal) binding to histones and targeting the NFKB/TLR/JAK/STAT signalling pathways, MYC and E2F1-regulated genes, cell cycle regulation and chromatin structure. It has strong anti-proliferative activity in different AML (acute myeloid leukemia) and MM (multiple myeloma) models through down-regulation of c-Myc levels and its downstream transcriptome (IC50 <100 nM in a TR-FRET assay). In vitro, BAY 1238097 showed strong inhibitory activity (IC50 < 100 nM) in a TR-FRET assay using BET BRD4 bromodomain 1 and an acetylated peptide derived from histone H4. In the NanoBRET assay, the interaction between BRD4, BRD3 or BRD2 and H4 was inhibited with IC50 values of 63 nM, 609 nM and 2430 nM, showing selectivity of the compound for BRD4. A strong reduction of c-Myc transcript and protein levels was observed in treated MOLM-13 (AML) and MOLP-8 (MM) cell lines. ChIP experiments performed in these models additionally revealed that BAY 1238097 prevented binding of BRD4 to c-Myc regulatory regions. In vivo, BAY 1238097 showed strong efficacy in the AML models THP-1, MOLM-13 and KG-1, with T/C between 13 and 20%. Overall, the compound was well tolerated at MTD, with body weight losses of 5-9% at nadir. BAY 1238097 was also active in MM models. Efficacy was observed against a human IGH-cyclin D1 translocated MOLP-8 model with a T/C of 3%, whereas the standard-of-care agents bortezomib and lenalidomide were inactive or poorly active. In this model, BAY 1238097 was well tolerated at 10 mg/kg applied over 14 days, with no body weight loss measured. BAY 1238097 was also active against the FGFR/MMSET translocated model NCIH929, with 19% T/C versus 49% T/C for the standard-of-care lenalidomide. The compound was well tolerated applied at 12 mg/kg for 9 days (maximum body weight loss 6%).
| ln Vitro |
BAY 1238097 demonstrated potent inhibitory action (IC50 < 100 nM) in a TR-FRET test employing an acetylated peptide sourced from histone H4 and BET BRD4 bromodomain 1. The interaction between H4 (IC50=2430 nM), BRD4 (IC50=63 nM), and BRD3 or BRD2 (IC50=609 nM) is suppressed in the NanoBRET experiment [1]. In lymphoma models, BAY 1238097 demonstrates anticancer efficacy in vitro. GCB DLBCL cells' gene expression is impacted by BAY 1238097. The most downregulated genes at the gene level were BTK, CCDC86, CCND2, CD19, CD27, FAIM, FCMR (FAIM3), IL7R, IRAK1, MAPK13, MYB, MYC, PDE4B, TNFRSF13B, and TNFRSF17. Genes that are up-regulated in addition to those that code for histones include CCL5, CDKN2C, CD69, JUN, and MKNK2 [2].
|
|---|---|
| ln Vivo |
Strong effectiveness was demonstrated by BAY 1238097 in AML and MM models. In lymphoma models, BAY 1238097 exhibits in vivo anticancer efficacy [1][2]. In several illness models, daily administration of BAY 1238097 at a dose of 10-15 mg/kg for 9–14 days was well tolerated and showed no signs of toxicity [1][2].
|
| Animal Protocol |
Animal/Disease Models: Severe combined immunodeficiency (SCID) female mice (9-12 weeks old) were inoculated subcutaneously (sc) (sc) in the right flank with 5×106 SU-DHL-8 cells/mouse, suspended in 0.1 mL Matrigel or treated with O.
Doses: 15 mg/kg (maximum tolerated dose). Route of Administration: Take orally daily for 12 days (day 21 after tumor inoculation). Experimental Results: demonstrated strong efficacy in AML models THP-1, MOLM-13 and KG-1 with T/C between 13% and 20%. It is also active in the MM model of the human IGH-cyclin D1 translocation MOLP-8 model with a T/C of 3% [2]. |
| References | |
| Additional Infomation |
BET Inhibitor BAY1238097 is an inhibitor of the Bromodomain (BRD) and Extra-Terminal domain (BET) family of proteins, with potential antineoplastic activity. Upon administration, the BET inhibitor BAY1238097 binds to the acetylated lysine recognition motifs on the BRD of BET proteins, thereby preventing the interaction between BET proteins and histones. This disrupts chromatin remodeling and prevents the expression of certain growth-promoting genes. This leads to an inhibition of tumor cell growth. BET proteins (BRD2, BRD3, BRD4 and BRDT) are transcriptional regulators that bind to acetylated lysines on the tails of histones H3 and H4, and regulate chromatin structure and function; they play an important role in the modulation of gene expression during development and cellular growth.
|
| Molecular Formula |
C25H33N5O3
|
|---|---|
| Molecular Weight |
451.561225652695
|
| Exact Mass |
451.258
|
| CAS # |
1564268-08-1
|
| Related CAS # |
(R)-BAY1238097;1564269-85-7
|
| PubChem CID |
118237331
|
| Appearance |
Light yellow to yellow solid powder
|
| LogP |
2.4
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
33
|
| Complexity |
688
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
C1(C2=CC=C(N3CCN(C)CC3)C=C2)C2=CC(OC)=C(OC)C=C2C[C@H](C)N(C(NC)=O)N=1
|
| InChi Key |
CJIPEACKIJJYED-KRWDZBQOSA-N
|
| InChi Code |
InChI=1S/C25H33N5O3/c1-17-14-19-15-22(32-4)23(33-5)16-21(19)24(27-30(17)25(31)26-2)18-6-8-20(9-7-18)29-12-10-28(3)11-13-29/h6-9,15-17H,10-14H2,1-5H3,(H,26,31)/t17-/m0/s1
|
| Chemical Name |
(S)-7,8-dimethoxy-N,4-dimethyl-1-(4-(4-methylpiperazin-1-yl)phenyl)-4,5-dihydro-3H-benzo[d][1,2]diazepine-3-carboxamide
|
| Synonyms |
S-isomer of BAY-1238097; BAY1238097; BAY-1238097; BAY 1238097; BAY 12-38097; BAY 123; BAY-123; BAY12-38097; BAY-12-38097
|
| 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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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 : ~150 mg/mL (~332.18 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.54 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 (5.54 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 (5.54 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 | 2.2145 mL | 11.0727 mL | 22.1455 mL | |
| 5 mM | 0.4429 mL | 2.2145 mL | 4.4291 mL | |
| 10 mM | 0.2215 mL | 1.1073 mL | 2.2145 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.
The BET inhibitor BAY 1238097 has anti‐proliferative activityinvitroandinvivoin models of B‐cell lymphomas. |
BAY 1238097 hasinvivoanti‐proliferative activity in models of diffuse large B‐cell lymphoma.Br J Haematol. 2017 Sep;178(6):936-948. |
BAY 1238097 affects the gene expression of GCB DLBCL cells.Br J Haematol. 2017 Sep;178(6):936-948. |
BAY 1238097 showsinvitrosynergism with the mTOR inhibitor everolimus. |
BAY 1238097 showsinvitrosynergism with EZH2 inhibitors with a decrease in EZH2 protein levels and H3K27me3.Br J Haematol. 2017 Sep;178(6):936-948. |
EZH2mutational status is associated with sensitivity to BAY 1238097 and both JQ1 and BAY 1238097 decrease BRD4 binding to EZH2 promoter region.Br J Haematol. 2017 Sep;178(6):936-948. |
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA
