| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
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| ln Vitro |
Dose-dependent disruption of the cell cycle was seen in MOLM-13 and, to a lesser extent, MV4-11 cells. Specifically, treatment with SEL24-B489 resulted in a marked decrease in the S phase, which was followed by PARP breakage and apoptosis [1]. S6 (S235/236) is strongly inhibited by SEL24-B489, although PI3K/mTOR signaling is not significantly impacted [1]. SEL24-B489 suppresses MCL1 expression and STAT5 (Ser726) without causing PARP cleavage or changing the amount of c-MYC [1].
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| ln Vivo |
In in vivo models of AML, SEL24-B489 (25–100 mg/kg, orally) shows efficacy [1]. At low/submicromolar concentrations, SEL24-B489 causes apoptosis in DLBCL cell lines and exhibits action in xenograft models [2].
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: AZD1208, AC220 and AraC in AML cell lines. Tested Concentrations: 0-10μM. Incubation Duration: 72 hrs (hours). Experimental Results: diminished vitality. |
| Animal Protocol |
Animal/Disease Models: SCID/beige mice bearing MV-4-11 tumors (FLT3-ITD+)[1].
Doses: 50, 75 and 100 mg/kg. Doses: Orally, twice (two times) daily. Experimental Results: Significant dose-dependent tumor reduction (tumor growth inhibition (TGI) of 67%, 74% and 82% at daily doses of 50, 75 and 100 mg/kg, respectively). |
| References |
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| Additional Infomation |
Dapolsertib is an orally available inhibitor of PIM family serine/threonine protein kinases and mutant forms of FMS-related tyrosine kinase 3 (FLT3; STK1) with potential antineoplastic activity. Upon oral administration, dapolsertib binds to and inhibits the kinase activities of PIM-1, -2 and -3, and mutant forms of FLT3, which may result in the interruption of the G1/S phase cell cycle transition, an inhibition of cell proliferation, and an induction of apoptosis in tumor cells that overexpress PIMs or express mutant forms of FLT3. FLT3, a tyrosine kinase receptor that is overexpressed or mutated in various cancers, plays a role in signaling pathways that regulate hematopoietic progenitor cell proliferation, and in leukemic cell proliferation and survival. PIM kinases, downstream effectors of many cytokine and growth factor signaling pathways, including the FLT3 signaling pathway, play key roles in cell cycle progression and apoptosis inhibition and may be overexpressed in various malignancies.
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| Molecular Formula |
C15H18BR2N4O2
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|---|---|
| Molecular Weight |
446.137021541595
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| Exact Mass |
445.977
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| CAS # |
1616359-00-2
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| Related CAS # |
1616359-00-2;1616359-00-2 (HCl);
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| PubChem CID |
76286825
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
3.5
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
23
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| Complexity |
442
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| Defined Atom Stereocenter Count |
0
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| SMILES |
BrC1C(=C(C2=C(C=1)N(C(C)C)C(C1CCNCC1)=N2)[N+](=O)[O-])Br
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| InChi Key |
UOUBCIJIWDLRGM-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C15H18Br2N4O2/c1-8(2)20-11-7-10(16)12(17)14(21(22)23)13(11)19-15(20)9-3-5-18-6-4-9/h7-9,18H,3-6H2,1-2H3
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| Chemical Name |
5,6-dibromo-4-nitro-2-piperidin-4-yl-1-propan-2-ylbenzimidazole
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO : ~25 mg/mL (~56.04 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.60 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 (5.60 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2414 mL | 11.2072 mL | 22.4145 mL | |
| 5 mM | 0.4483 mL | 2.2414 mL | 4.4829 mL | |
| 10 mM | 0.2241 mL | 1.1207 mL | 2.2414 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.
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