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Purity: ≥98%
SJ000291942 is a new small-molecule activator of the canonical BMP (bone morphogenetic proteins) signaling pathway. BMPs are members of the transforming growth factor beta (TGFβ) family of secreted signaling molecules. SJ000291942 was found by high throughput screening of a library of ∼600 000 small molecules. Using a cell-based luciferase assay in the BMP4-responsive human cervical carcinoma clonal cell line, C33A-2D2, SJ000291942 can ventralize zebrafish embryos and stimulate increased expression of the BMP target genes, bmp2b and szl. Because SJ000291942 ventralizes zebrafish embryos, it was termed as 'ventromorphins.' As expected for a BMP pathway activator, SJ000291942 induces the differentiation of C2C12 myoblasts to osteoblasts. Affymetrix RNA analysis confirmed the differentiation results and showed that SJ000291942 treatment elicits a genetic response similar to BMP4 treatment. Unlike isoliquiritigenin (SJ000286237), a flavone that maximally activates the pathway after 24 h of treatment, SJ000291942 induced SMAD1/5/8 phosphorylation within 30 min of treatment and achieved peak activity within 1 h, indicating that their responses are consistent with directly activating BMP signaling.
| ln Vitro |
SJ000291942 was the most powerful and the most severe ventralization was observed in embryos treated with it. At lesser dosages, SJ000291942 likewise produced greater mortality than the other two drugs and the control group. This is consistent with an increase in BMP signaling activity and suggests that our drugs induce embryonic ventralization. SJ000291942 led to upregulated bmp2b and szl expression. The conventional BMP signaling pathway is activated by SJ000291842, as demonstrated by zebrafish test. Immunoblotting was done on protein lysates from C33A-2D2 cells treated with SJ000291942 at various intervals in order to expand on these findings. In a serum-free media, SJ000291942 triggers the phosphorylation of SMAD1/5/8. The most active was SJ000291842, just like in zebrafish embryos. After one hour of treatment, SJ000291942 maximally promotes p-SMAD1/5/8. Phosphorylated extracellular signal-regulated protein kinase ERK1/2 (P-ERK1/2) was considerably increased by SJ000291942, according to immunoblot examination of C33A-2D2 lysates treated with the drug. The gene expression fingerprints obtained by treatment with the highest dosages (100 and 300ng) of BMP4 were most similar to osteoblastic expression. Treatment with low dose (10ng) BMP4 was closely associated with treatment with 25μM Compound 3 and 25μM SJ000291942[1].
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| References |
[1]. Genthe JR, et al. Ventromorphins: A New Class of Small Molecule Activators of the Canonical BMP Signaling Pathway. ACS Chem Biol. 2017 Sep 15;12(9):2436-2447.
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| Molecular Formula |
C₁₆H₁₅FN₂O₄
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| Molecular Weight |
318.30
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| CAS # |
425613-09-8
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| SMILES |
O=C(NC1=CC=C(F)C([N+]([O-])=O)=C1)COC2=CC=C(CC)C=C2
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.85 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 (7.85 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 25.0 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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.1417 mL | 15.7085 mL | 31.4169 mL | |
| 5 mM | 0.6283 mL | 3.1417 mL | 6.2834 mL | |
| 10 mM | 0.3142 mL | 1.5708 mL | 3.1417 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.
Summary of the high-throughput screen and hit identification.ACS Chem Biol. 2017 Sep 15; 12(9): 2436–2447. |
Structure Activity Relationship (SAR) study using cScore, EC50 and zebrafish phenotypic screen.ACS Chem Biol. 2017 Sep 15; 12(9): 2436–2447. |
Dose-response of the three compounds in ventralization of zebrafish embryos. |
Transcriptional profiling by Affymetrix assay.ACS Chem Biol. 2017 Sep 15; 12(9): 2436–2447.
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Differentiation of myoblastic C2C12 cells to osteoblasts.ACS Chem Biol. 2017 Sep 15; 12(9): 2436–2447. |
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