PROTAC FLT3/CDKs degrader-1
Based on 1 Customer Validation
PROTAC FLT3/CDKs degrader-1 is a PROTAC degrader targeting CDKs and FLT3. PROTAC FLT3/CDKs degrader-1 degrades CDK2, CDK4, CDK6, CDK9 and FLT3 proteins via a ubiquitin-proteasome-dependent bivalent mechanism, with a DC50 of 18.73 nM against CDK2. PROTAC FLT3/CDKs degrader-1 promotes myeloid cell differentiation. PROTAC FLT3/CDKs degrader-1 inhibits leukemia cell proliferation. PROTAC FLT3/CDKs degrader-1 can be used for the research of acute myeloid leukemia.
(Pink: FLT3 and CDK2 and CDK4 and CDK6 and CDK9 ligand (HY-161709); Blue: Cereblon ligand (HY-W087383); Black: linker (HY-W012935)).
For research use only. We do not sell to patients.
- Purity : 98.21%
- CAS No.: 3075001-08-7
- Formula: C40H42N12O5
- Molecular Weight:770.84
-
Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
-
Biological Activity
-
Chemical Information
-
Solvent & Solubility
- Purity & Documentation
- References
-
Help & FAQs
All PROTACs Isoforms
More
Biological Activity
Description
IC50 & Target
[1]|
CDK2 18.73 nM (DC50) |
CDK4 |
CDK6 |
CDK9 |
Cellular Effect
|
Cell Line
|
Type | Value | Description | References |
|---|---|---|---|---|
| HL-60 | IC50 |
10.49 nM
Compound: C3
|
Antiproliferative activity against human HL-60 cells measured after 1 to 3 days by CCK-8 assay
Antiproliferative activity against human HL-60 cells measured after 1 to 3 days by CCK-8 assay
|
[PMID: 38878515] |
| Kasumi 1 | IC50 |
3.99 nM
Compound: C3
|
Antiproliferative activity against human Kasumi 1 cells measured after 1 to 3 days by CCK-8 assay
Antiproliferative activity against human Kasumi 1 cells measured after 1 to 3 days by CCK-8 assay
|
[PMID: 38878515] |
| MOLM-13 | IC50 |
4.52 nM
Compound: C3
|
Antiproliferative activity against human MOLM-13 cells measured after 1 to 3 days by CCK-8 assay
Antiproliferative activity against human MOLM-13 cells measured after 1 to 3 days by CCK-8 assay
|
[PMID: 38878515] |
| MV4-11 | IC50 |
2.9 nM
Compound: C3
|
Antiproliferative activity against human MV4-11 cells measured after 1 to 3 days by CCK-8 assay
Antiproliferative activity against human MV4-11 cells measured after 1 to 3 days by CCK-8 assay
|
[PMID: 38878515] |
| NB-4 | IC50 |
4.94 nM
Compound: C3
|
Antiproliferative activity against human NB4 cells measured after 1 to 3 days by CCK-8 assay
Antiproliferative activity against human NB4 cells measured after 1 to 3 days by CCK-8 assay
|
[PMID: 38878515] |
| OCI-AML2 | IC50 |
17.85 nM
Compound: C3
|
Antiproliferative activity against human OCI-AML2 cells measured after 1 to 3 days by CCK-8 assay
Antiproliferative activity against human OCI-AML2 cells measured after 1 to 3 days by CCK-8 assay
|
[PMID: 38878515] |
| THP-1 | IC50 |
37.08 nM
Compound: C3
|
Antiproliferative activity against human THP-1 cells measured after 1 to 3 days by CCK-8 assay
Antiproliferative activity against human THP-1 cells measured after 1 to 3 days by CCK-8 assay
|
[PMID: 38878515] |
In Vitro
PROTAC FLT3/CDKs degrader-1 (Compound C3) (0.03-500 nM; 0-36 h) potently degrades CDK2 in HL-60 cells, with a DC50 of 18.73 nM. Degradation initiates at 12 h, and the agent acts via a ubiquitin-proteasome-dependent bivalent mechanism[1].
PROTAC FLT3/CDKs degrader-1 (2 nM; unspecified concentration for DC50 determination) selectively degrades CDK2/CDK4/CDK6/CDK9 and FLT3 (including FLT3-ITD) in HL-60, MV4-11, KASUMI-1 and THP-1 human acute myeloid leukemia (AML) cells. It exhibits the strongest degradation activity against FLT3-ITD in MV4-11 cells, and shows no significant effects on CDK1 or CDK5[1].
PROTAC FLT3/CDKs degrader-1 (1-6.25 nM; 3-5 days) potently induces myeloid differentiation of HL-60 cells, with the proportion of CD11b-positive cells reaching 72.77% after treatment with 6.25 nM for 5 days[1].
PROTAC FLT3/CDKs degrader-1 exhibits broad antiproliferative activity in human acute myeloid leukemia (AML) cell lines, with the highest potency in MV4-11 cells (IC50 = 2.90 nM) and the lowest potency in THP-1 cells (IC50 = 37.08 nM)[1].
PROTAC FLT3/CDKs degrader-1 forms stable ternary complexes with CDK2 and CRBN through multiple specific intermolecular interactions, and also forms stable complexes with HPK1 and CRBN[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Cell Line:HL-60 human acute promyelocytic leukemia cells
-
Concentration:0.03, 0.1, 0.2, 0.7, 2.1, 6.2, 19, 56, 167, 500 nM (dose-response); 10 nM (time-course; inhibitor pretreatment)
-
Incubation Time:24 h (dose-response; inhibitor pretreatment); 0, 4, 8, 12, 24, 36 h (time-course)
-
Result:Degraded CDK2 with a DC50 of 18.73 nM and a maximum degradation (Dmax) of 86.83%.
First detected CDK2 degradation 12 h after treatment with 10 nM of the degrader.
Abolished degrader-induced CDK2 degradation when cells were pretreated with proteasome inhibitor MG132, NEDD8-activated E1 enzyme inhibitor MLN4924, CRBN ligand Thalidomide, or CDK2 inhibitor FN-1501.
-
Cell Line:HL-60 human acute promyelocytic leukemia cells
-
Concentration:1, 2, 4, 6.25 nM
-
Incubation Time:3, 5 days
-
Result:Induced a concentration-dependent increase in CD11b expression, with stronger differentiation observed after 5 days compared to 3 days.
Stimulated 72.77% CD11b-positive cells at 6.25 nM on day 5, which was 7.2 times higher than the control group (10.08% on day 5) and 2.1 times higher than the positive control CPS2 (34.39% at 500 nM on day 5).
Induced 59.80% CD11b-positive cells at 6.25 nM on day 3, which was 5.7 times higher than the control group and 2.2 times higher than CPS2 (26.84% at 500 nM on day 3).
Chemical Information
-
CAS No. 3075001-08-7
-
Appearance Solid
-
Molecular Weight 770.84
-
Formula C40H42N12O5
-
Color Light yellow to yellow
-
SMILES
O=C(NC1=O)CCC1N(C2=O)C(C3=C2C=CC(N(CC4)CCC4CN(CC5)CCN5CC6=CC=C(NC(C7=NNC=C7NC8=C9C(NC=C9)=NC=N8)=O)C=C6)=C3)=O
-
Shipping
Room temperature in continental US; may vary elsewhere.
-
Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvent & Solubility
In Vitro:
DMSO : 100 mg/mL (129.73 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (3.24 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (3.24 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
-
-
-
-
Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
-
%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
-
%+
-
+%Tween-80 + +
-
%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Purity & Documentation
-
Data Sheet (275 KB)
-
SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
-
Handling Instructions (2659 KB)
References
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.2973 mL | 6.4864 mL | 12.9729 mL | 32.4322 mL |
| 5 mM | 0.2595 mL | 1.2973 mL | 2.5946 mL | 6.4864 mL | |
| 10 mM | 0.1297 mL | 0.6486 mL | 1.2973 mL | 3.2432 mL | |
| 15 mM | 0.0865 mL | 0.4324 mL | 0.8649 mL | 2.1621 mL | |
| 20 mM | 0.0649 mL | 0.3243 mL | 0.6486 mL | 1.6216 mL | |
| 25 mM | 0.0519 mL | 0.2595 mL | 0.5189 mL | 1.2973 mL | |
| 30 mM | 0.0432 mL | 0.2162 mL | 0.4324 mL | 1.0811 mL | |
| 40 mM | 0.0324 mL | 0.1622 mL | 0.3243 mL | 0.8108 mL | |
| 50 mM | 0.0259 mL | 0.1297 mL | 0.2595 mL | 0.6486 mL | |
| 60 mM | 0.0216 mL | 0.1081 mL | 0.2162 mL | 0.5405 mL | |
| 80 mM | 0.0162 mL | 0.0811 mL | 0.1622 mL | 0.4054 mL | |
| 100 mM | 0.0130 mL | 0.0649 mL | 0.1297 mL | 0.3243 mL |
PROTAC FLT3/CDKs degrader-1 Related Classifications
HY-161708 Related Classifications
Powered by Bioz