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| Targets |
CCL241736 targets FLT3 (FMS-like tyrosine kinase 3) and Aurora kinases (Aurora-A and Aurora-B). FLT3 is a receptor tyrosine kinase that plays a critical role in hematopoietic stem cell proliferation and differentiation, and its mutations are commonly found in acute myeloid leukemia (AML). Aurora kinases are key regulators of mitosis. By inhibiting these kinases, CCT241736 disrupts cell cycle progression and survival signaling in cancer cells.
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| ln Vitro |
CCT241736 (Compound 27e) is a strong, orally accessible dual inhibitor of FLT3 and Aurora kinase. It inhibits FLT3 kinase (Kd, 6.2 nM), FLT3 mutants (Kd, 38 nM), and FLT3-A (Kd, 7.5 nM, IC50, 38 nM, Aurora-B Kd, 48 nM). A variety of human tumor cell lines, including human colon cancer HCT116 (GI50, 0.300 μM), human FLT3-ITD positive AML cell lines MOLM-13 (GI50, 0.104 μM), and MV4-11 (GI50, 0.291μM), demonstrate antiproliferative activity in response to CCT241736. Additionally, CCT241736 has a significant effect via inhibiting histone H3 phosphorylation at S10 (a biomarker for Aurora-B inhibition; IC50, 0.148 μM) and autophosphorylation of Aurora-A at T288 (a biomarker for Aurora-A inhibition; IC50, 0.030 μM). Cell viability is compared between Aurora-A and -B. In MOLM-13 cells, CCT241736 suppresses Aurora-A while also inhibiting FLT3 signaling [1].
CCT241736 is a potent dual inhibitor of FLT3 and Aurora kinases. It inhibits Aurora-A with a Kd of 7.5 nM and an IC50 of 38 nM, and Aurora-B with a Kd of 48 nM. It inhibits FLT3 kinase with a Kd of 6.2 nM, and FLT3 mutants including FLT3-ITD (Kd 38 nM) and FLT3(D835Y) (Kd 14 nM). It also inhibits the activity of 22 additional kinases by greater than 90% at 1 µM. |
| ln Vivo |
When taken orally at 100 mg/kg twice day, CCT241736 (50, 100 mg/kg, bid, po) entirely eradicates tumors and slows the growth of MV4-11 human tumor xenografts in a dose-dependent manner [1].
CCT241736 is an orally bioavailable compound. Specific in vivo activity data is not extensively detailed in the available literature, but its potent inhibition of FLT3 and Aurora kinases suggests potential for the treatment of cancers such as acute myeloid leukemia. Further studies are needed to fully characterize its in vivo efficacy and pharmacokinetic properties. |
| Enzyme Assay |
CCT241736's activity as a kinase inhibitor is assessed using in vitro kinase assays that measure its ability to inhibit FLT3 and Aurora kinase activity. Kd values are determined using binding assays such as surface plasmon resonance or competition binding assays. IC50 values are determined from dose-response curves in functional assays.
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| Cell Assay |
Cellular assays for CCT241736 involve treating cancer cell lines, such as those from acute myeloid leukemia, with the compound and measuring cell proliferation and viability. The compound's ability to inhibit FLT3 and Aurora kinase signaling is assessed by Western blot analysis of downstream targets. Its effects on cell cycle progression and apoptosis can also be evaluated.
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| Animal Protocol |
In vivo animal model protocols for CCT241736 would involve its oral administration to tumor-bearing mice, particularly models of FLT3-mutant acute myeloid leukemia. The compound's antitumor efficacy is assessed by measuring tumor growth inhibition. Pharmacodynamic markers, such as FLT3 and Aurora kinase phosphorylation, are measured in tumor tissues to confirm target engagement.
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| ADME/Pharmacokinetics |
CCT241736 is an orally bioavailable compound. It has a molecular weight of 456.37 and a molecular formula of C22H23Cl2N7. Specific pharmacokinetic parameters, such as bioavailability and half-life, are not detailed in the available literature.
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| Toxicity/Toxicokinetics |
Specific toxicological data for CCT241736 is not extensively detailed in the available literature. As a research compound, it is intended for research use only and not for human consumption. Standard safety assessments would be required for clinical development.
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| References | |
| Additional Infomation |
EP0042, an aurora kinase/FLT3 inhibitor, is an orally bioavailable inhibitor of the serine/threonine protein kinase Aurora kinase and FMS-associated tyrosine kinase 3 (FLT3; STK1; CD135; FLK2) with potential antitumor activity. After oral administration, EP0042 specifically binds to and inhibits Aurora kinase and FLT3, thereby interfering with the activation of Aurora kinase and FLT3-mediated signal transduction pathways. This may lead to disruption of mitotic spindle assembly, disordered chromosome segregation, and inhibition of proliferation in tumor cells overexpressing Aurora kinase and/or FLT3. Aurora kinase plays a crucial role in the mitotic checkpoint control during mitosis. Aurora kinase and FLT3 are overexpressed in various cancers and play a key role in tumor cell proliferation.
CCT241736 (CAS# 1402709-93-6) is a research compound used to study FLT3 and Aurora kinase function in cancer. It is a potent and orally bioavailable dual FLT3 and Aurora kinase inhibitor. It has a molecular weight of 456.37 and a molecular formula of C22H23Cl2N7. It is not approved for clinical use and is intended for research purposes only. |
| Molecular Formula |
C22H23CL2N7
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|---|---|
| Molecular Weight |
456.375
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| Exact Mass |
455.139
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| Elemental Analysis |
C, 57.90; H, 5.08; Cl, 15.54; N, 21.48
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| CAS # |
1402709-93-6
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| PubChem CID |
71454279
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| Appearance |
White to off-white solid powder
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| Density |
1.5±0.1 g/cm3
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| Index of Refraction |
1.727
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| LogP |
4.55
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
31
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| Complexity |
596
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C12NC(C3=CN(C)N=C3C)=NC1=C(N1CCN(CC3=CC=C(Cl)C=C3)CC1)C(Cl)=CN=2
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| InChi Key |
AKJBLKUZXRMECW-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H23Cl2N7/c1-14-17(13-29(2)28-14)21-26-19-20(18(24)11-25-22(19)27-21)31-9-7-30(8-10-31)12-15-3-5-16(23)6-4-15/h3-6,11,13H,7-10,12H2,1-2H3,(H,25,26,27)
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| Chemical Name |
6-chloro-7-[4-[(4-chlorophenyl)methyl]piperazin-1-yl]-2-(1,3-dimethylpyrazol-4-yl)-1H-imidazo[4,5-b]pyridine
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| Synonyms |
CCT 241736; CCT-241736; CCT241736
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| HS Tariff Code |
2934.99.03.00
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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 : ~12.5 mg/mL (~27.39 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (5.48 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with heating and sonication.
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 (5.48 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with heating and sonication. 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.48 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1912 mL | 10.9558 mL | 21.9116 mL | |
| 5 mM | 0.4382 mL | 2.1912 mL | 4.3823 mL | |
| 10 mM | 0.2191 mL | 1.0956 mL | 2.1912 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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