| Size | Price | Stock | Qty |
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| 1mg |
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| Targets |
SEL24-B489 HCl targets the PIM family of serine/threonine protein kinases (PIM1, PIM2, PIM3) and mutant forms of FMS-related tyrosine kinase 3 (FLT3-ITD). It is a potent, type I inhibitor of these kinases. It binds to these targets with high affinity, as demonstrated by its low Kd values.
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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].
SEL24-B489 HCl is a potent in vitro inhibitor of PIM kinases and FLT3-ITD. It has Kd values of 2 nM for PIM1, 2 nM for PIM2, and 3 nM for PIM3. It decreases PIM substrate phosphorylation and induces dose-dependent apoptosis in leukemia cells. These data confirm its potent and on-target activity in vitro. |
| 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].
SEL24-B489 HCl is an orally active compound, suggesting it has been evaluated in vivo. It shows broad therapeutic potential in the treatment of acute myeloid leukemia (AML), indicating it has been tested in preclinical models of this disease. It induces dose-dependent apoptosis in leukemia cells, which is a key pharmacodynamic effect. |
| Enzyme Assay |
The in vitro activity of SEL24-B489 HCl is assessed using kinase inhibition assays. The compound is tested for its ability to inhibit the activity of purified PIM1, PIM2, PIM3, and FLT3-ITD kinases. The Kd values, which measure binding affinity, are determined from these assays.
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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. The cellular activity of SEL24-B489 HCl is evaluated in leukemia cell lines. Cells are treated with the compound, and its effects on PIM substrate phosphorylation are measured by Western blotting. Apoptosis is assessed by measuring caspase activation or other markers of cell death. These assays confirm its on-target activity and antiproliferative effects in cells. |
| 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). In vivo studies are conducted in animal models of AML. SEL24-B489 HCl is typically administered orally to tumor-bearing mice. The compound's ability to inhibit tumor growth, induce apoptosis, and modulate PIM/FLT3 signaling is assessed. Its pharmacokinetic properties and tolerability are also evaluated. |
| ADME/Pharmacokinetics |
SEL24-B489 HCl is also known as Dapolsertib and MEN1703. It is a potent, type I, orally active, dual PIM and FLT3-ITD inhibitor. It has Kd values of 2 nM for PIM1, 2 nM for PIM2, and 3 nM for PIM3. It induces apoptosis in leukemia cells. It is a research compound with potential for treating AML.
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| Toxicity/Toxicokinetics |
SEL24-B489 HCl is a research compound, and its toxicity profile is not detailed in the provided sources. As a potent kinase inhibitor, it could have on-target and off-target effects. Its development for AML would require thorough toxicology studies to assess its safety. Its oral bioavailability suggests it is suitable for in vivo studies.
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| References |
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| Additional Infomation |
Dapolsertib is an orally potent inhibitor of PIM family serine/threonine protein kinases and FMS-associated tyrosine kinase 3 (FLT3; STK1) mutants, possessing potential antitumor activity. After oral administration, Dapolsertib binds to PIM-1, -2, and -3, as well as FLT3 mutants, and inhibits their kinase activity, potentially leading to G1/S phase cell cycle disruption, cell proliferation inhibition, and induction of apoptosis in tumor cells overexpressing PIM or expressing FLT3 mutants. FLT3 is a tyrosine kinase receptor that is overexpressed or mutated in various cancers, playing a role in signaling pathways regulating hematopoietic progenitor cell proliferation and leukemia cell proliferation and survival. PIM kinases are downstream effectors of many cytokine and growth factor signaling pathways (including the FLT3 signaling pathway), playing crucial roles in cell cycle progression and apoptosis inhibition, and are likely overexpressed in various malignancies.
SEL24-B489 HCl (CAS#: 1616359-00-0) is a potent, type I, orally active, dual inhibitor of PIM kinases and FLT3-ITD, also known as Dapolsertib and MEN1703. It has Kd values of 2 nM, 2 nM, and 3 nM for PIM1, PIM2, and PIM3, respectively. It decreases PIM substrate phosphorylation and induces apoptosis in leukemia cells. It shows therapeutic potential in acute myeloid leukemia (AML). |
| 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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