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BCI-121

Alias: BCI-121 BCI 121 BCI121
Cat No.:V6240 Purity: ≥98%
BCI-121 is a SMYD3 inhibitor that can suppress cancer/tumor cell growth/proliferation.
BCI-121
BCI-121 Chemical Structure CAS No.: 432529-82-3
Product category: Histone Methyltransferase
This product is for research use only, not for human use. We do not sell to patients.
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Purity & Quality Control Documentation

Purity: ≥98%

Product Description
BCI-121 is a SMYD3 inhibitor that can suppress cancer/tumor cell growth/proliferation.
Biological Activity I Assay Protocols (From Reference)
ln Vitro
BCI-121 efficiently lowers the proliferation of different cancer cell types by substantially inhibiting chromatin recruitment and SMYD3-substrate interaction. After 72 hours, BCI-121 dramatically decreased the HT29 (46% reduction) and HCT116 (54% reduction) cells' ability to proliferate, as well as the expression levels of the SMYD3 target genes. Histone H4 is preferentially methylated by SMYD3, and in vitro SMYD3-mediated H4 methylation is inhibited by BCI-121. Cancer cells treated with BCI-121 had much less growth potential, which accumulated in the S phase of the cell cycle. Targeted methyl marks (H4K5me and H3K4me2) were reduced and cell proliferation was inhibited in a dose-dependent manner in response to BCI-121 treatment. In cancer cell lines overexpressing SMYD3, BCI-121 has antiproliferative characteristics and typically resembles the effects of RNAi targeting SMYD3. BCI-121 inhibits SMYD3 from recruiting to the promoters of its target genes, an event linked to decreased gene expression, according to experiments conducted in cancer cells [1].
References

[1]. A SMYD3 Small-Molecule Inhibitor Impairing Cancer Cell Growth. J Cell Physiol. 2015 Oct;230(10):2447-2460.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Exact Mass
339.058
CAS #
432529-82-3
Related CAS #
432529-82-3
PubChem CID
795875
Appearance
Light yellow to yellow solid powder
Density
1.5±0.1 g/cm3
Boiling Point
576.1±50.0 °C at 760 mmHg
Flash Point
302.2±30.1 °C
Vapour Pressure
0.0±1.6 mmHg at 25°C
Index of Refraction
1.619
LogP
1.8
Hydrogen Bond Donor Count
2
Hydrogen Bond Acceptor Count
3
Rotatable Bond Count
4
Heavy Atom Count
20
Complexity
348
Defined Atom Stereocenter Count
0
SMILES
NC(C1CCN(CC(NC2=CC=C(Br)C=C2)=O)CC1)=O
InChi Key
KSUYPIXCRPCPGF-UHFFFAOYSA-N
InChi Code
InChI=1S/C14H18BrN3O2/c15-11-1-3-12(4-2-11)17-13(19)9-18-7-5-10(6-8-18)14(16)20/h1-4,10H,5-9H2,(H2,16,20)(H,17,19)
Chemical Name
4-(Aminocarbonyl)-N-(4-bromophenyl)-1-piperidineacetamide
Synonyms
BCI-121 BCI 121 BCI121
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 Data
Solubility (In Vitro)
DMSO : ≥ 100 mg/mL (~293.93 mM)
Solubility (In Vivo)
Solubility in Formulation 1: ≥ 2.75 mg/mL (8.08 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 27.5 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: ≥ 2.75 mg/mL (8.08 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 27.5 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.

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Solubility in Formulation 3: ≥ 2.75 mg/mL (8.08 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 27.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.


 (Please use freshly prepared in vivo formulations for optimal results.)
Calculator

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What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?
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  • The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

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What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
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Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
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In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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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.

Biological Data
  • Virtual screening procedure allowing identification of BCI-121 as a promising candidate for SMYD3 inhibition. (A) Structure of full-length SMYD3 highlighting the N-terminal SET domain (purple), the MYND domain (yellow), the post-SET domain (gray), and the C-terminal region (blue). The boxes define the area of the protein - centered on the histone binding site - that was considered to perform the docking screening calculation. The green box identifies the area containing at least one atom of the putative ligand, while the purple box identifies the area where all atoms of the ligands should lie. (B) Schematic representation of the virtual screening procedure. (C) Compound 5 [BCI-121] is the best candidate small molecule for SMYD3 inhibition among the initial set of 15 compounds selected through the virtual screening procedure. The global level of SMYD3 targeted [H3K4me2 and H3K4me3] and non-targeted [H3K27me3] histone methyl marks was measured by immunoblot in nuclear enriched fractions of CRC cells (HT29) treated with each compound (100 μM). Values shown correspond to histone methyl mark levels quantified by densitometric analysis and normalized to the loading control Lamin A/C (arbitrary units, untreated control at 48h = 1).[1].Peserico A, et al. A SMYD3 Small-Molecule Inhibitor Impairing Cancer Cell Growth. J Cell Physiol. 2015 Oct;230(10):2447-2460
  • BCI-121 inhibits SMYD3 activity in vitro and in CRC cell models and affects cell proliferation. (A) In vitro methylation assay using the indicated recombinant SMYD3 protein on a mixture of calf thymus histones in the presence and/or absence of BCI-121 showing a significant decrease in H4 methylation. Autoradiograph and Coomassie stained (loading control) gels are shown. BCI-121 inhibits cell proliferation in HT29 (B) and HCT116 (C) cells in a dose- and time-dependent manner. Cell proliferation was assessed by cell counting. The data presented are the mean values obtained for each analyzed time point (n = 4). (D, E) BCI-121 100 μM decreases the expression levels of SMYD3 target genes in both cell lines (the 48 h time point was evaluated). β-actin was used for normalization of real-time PCR data. Statistical analysis was performed using Student’s t-tail test; *P < 0.05, **P < 0.01, and ***P < 0.001 were considered statistically significant.[1].Peserico A, et al. A SMYD3 Small-Molecule Inhibitor Impairing Cancer Cell Growth. J Cell Physiol. 2015 Oct;230(10):2447-2460
  • Basal SMYD3 expression levels predict BCI-121 treatment response. (A) Administration of BCI-121 affects proliferation of CRC cell lines expressing high levels of SMYD3. (B) BCI-121 treatment reduces targeted histone methyl marks [H4K5me and H3K4me2] to an extent comparable to that observed with RNAi. CRC cells were treated with BCI-121 and/or SMYD3-specific siRNAs for 48 h and H4K5me and H3K4me2 global levels were evaluated by immunoblot. H3 was used as a loading control. (C) SMYD3 protein is highly expressed in several cell lines derived from different types of cancer (A549 = lung cancer; Capan-1 = pancreatic cancer; Hep3b = hepatocellular carcinoma; MDA-MB-468 = breast cancer; DU145 and LnCap = prostate cancer; OVCAR-3 and SKOV-3 = ovarian cancer). β-tubulin was used as a loading control. (D) BCI-121 treatment impaired proliferation of cancer cells with high expression levels of SMYD3, while cancer cells expressing low levels of SMYD3 were not affected. [1].Peserico A, et al. A SMYD3 Small-Molecule Inhibitor Impairing Cancer Cell Growth. J Cell Physiol. 2015 Oct;230(10):2447-2460
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