Physicochemical Properties
| Molecular Formula | C18H16N2O2 |
| Molecular Weight | 292.331844329834 |
| Exact Mass | 292.121 |
| CAS # | 353495-21-3 |
| PubChem CID | 2967505 |
| Appearance | Light yellow to yellow solid powder |
| LogP | 4.2 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 3 |
| Rotatable Bond Count | 1 |
| Heavy Atom Count | 22 |
| Complexity | 453 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | [O-][N+](C1C=CC2=C(C=1)C1C=CCC1C(C1C=CC=CC=1)N2)=O |
| InChi Key | FBKCRWSTGRHOGI-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C18H16N2O2/c21-20(22)13-9-10-17-16(11-13)14-7-4-8-15(14)18(19-17)12-5-2-1-3-6-12/h1-7,9-11,14-15,18-19H,8H2 |
| Chemical Name | 8-nitro-4-phenyl-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinoline |
| 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: This product requires protection from light (avoid light exposure) during transportation and storage. |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | IC50: 0.1-1 μM (BAP1)[1] |
| ln Vitro | BAP1-IN-1 (Compound 8) (1 μM; 30 min) selectively inhibits BAP1 in a cellular setting as well as in vitro[1]. BAP1-IN-1 (0.1 μM; 24 h) dramatically modifies 240 genes in BAP1-WT cells, whereas only 33 transcripts are altered in BAP1-KO cells, indicating that BAP1 protein is mostly required for the changes in gene expression[1]. Cells with mutations in ASXL1 GOF are preferentially inhibited by BAP1-IN-1 (0-10 μM; 72 h)[1]. |
| ln Vivo | BAP1-IN-1 (Compound 8) (50 mg/kg/d; ip; 4 weeks) delays the progression of ASXL1-mutant leukemia and improves survival in mice[1]. |
| Cell Assay |
Western Blot Analysis[1] Cell Types: CAL51 cells Tested Concentrations: 1 μM Incubation Duration: 30 min Experimental Results: Remarkably inhibited BAP1 catalytic activity. Cell Viability Assay[1] Cell Types: THP1, MOML13 , K562, THP1-ASXL1-WT and THP1-ASXL1-Y591fs cells Tested Concentrations: 0, 0.1, 0.3, 1, 3 and 10 μM Incubation Duration: 72 h Experimental Results: K562 cells (ASXL1-Y591*) were Dramatically more sensitive to the treatment. Cells with ASXL1fs mutations were ten times more sensitive to the treatment. |
| Animal Protocol |
Animal/Disease Models: NSGS mice, K562 (ASXL1-WT /Y591*) xenograft model and patient-derived tumor cells (ASXL1-WT/Q588*) model[1] Doses: 50 mg/kg/d Route of Administration: intraperitoneal (ip) injection, drug treatments were started at day 28 after transplantation Experimental Results: Dramatically delayed progression of disease in both models. |
| References |
[1]. Epigenetic targeted therapy of stabilized BAP1 in ASXL1 gain-of-function mutated leukemia. Nat Cancer. 2021 May;2(5):515-526. |
Solubility Data
| Solubility (In Vitro) | DMSO: 50 mg/mL (171.04 mM) |
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.4208 mL | 17.1040 mL | 34.2079 mL | |
| 5 mM | 0.6842 mL | 3.4208 mL | 6.8416 mL | |
| 10 mM | 0.3421 mL | 1.7104 mL | 3.4208 mL |