dCDK9-202
Based on 1 Customer Validation
dCDK9-202 is a CDK9 PROTAC degrader with a DC50 of 3.5 nM. dCDK9-202 induces CDK9 degradation via the ubiquitin-proteasome system. dCDK9-202 inhibits the growth of cancer cells in vitro and suppresses tumor growth in mouse xenograft models. dCDK9-202 is applicable for cancer-related research.
(Pink: CDK9 ligand (HY-10008); Blue: Cereblon ligand (HY-W248665); Black: linker (HY-N8015)).
Para uso exclusivo en investigación. No vendemos a pacientes.
- Pureza: 98.74%
- Fòrmula: C40H49N7O7S2
- Peso molecular:803.99
-
Almacenamiento: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]
-
Actividad biológica
-
Chemical Information
-
Solvente y solubilidad
- Pureza y Documentación
- Referencias
-
Help & FAQs
Ver todos los productos específicos de isoformas PROTACs
MoreVer todos los productos específicos de isoformas Caspase
More
Actividad biológica
Descripciòn
IC50 & Target
[1]|
CDK9 3.5 nM (DC50) |
Caspase-3 |
Caspase-7 |
CDK4 |
CDK5 |
CDK6 |
CDK8 |
CDK11 |
IKZF3 |
Bcl-xL |
Cellular Effect
|
Cell Line
|
Type | Value | Description | References |
|---|---|---|---|---|
| SK-UT-1 | DC50 |
<10 nM
|
CDK9 degradation in human SKUT1 uterine leiomyosarcoma cells measured by Western blotting after 6 h treatment.
CDK9 degradation in human SKUT1 uterine leiomyosarcoma cells measured by Western blotting after 6 h treatment.
|
41066447 |
| A-375 | IC50 |
83.3 nM
|
Antiproliferative activity against human A-375 melanoma cells assessed as reduction in cell viability incubated for 72 hrs by MTT assay.
Antiproliferative activity against human A-375 melanoma cells assessed as reduction in cell viability incubated for 72 hrs by MTT assay.
|
41066447 |
| MES-SA | IC50 |
85.3 nM
|
Antiproliferative activity against human MES-SA uterine sarcoma cells assessed as reduction in cell viability incubated for 72 hrs by MTT assay.
Antiproliferative activity against human MES-SA uterine sarcoma cells assessed as reduction in cell viability incubated for 72 hrs by MTT assay.
|
41066447 |
| MDA-MB-231 | IC50 |
79.6 nM
|
Antiproliferative activity against human MDA-MB-231 breast cancer cells assessed as reduction in cell viability incubated for 72 hrs by MTT assay.
Antiproliferative activity against human MDA-MB-231 breast cancer cells assessed as reduction in cell viability incubated for 72 hrs by MTT assay.
|
41066447 |
| A673 | IC50 |
75.4 nM
|
Antiproliferative activity against human A-673 Ewing sarcoma cells assessed as reduction in cell viability incubated for 72 hrs by MTT assay.
Antiproliferative activity against human A-673 Ewing sarcoma cells assessed as reduction in cell viability incubated for 72 hrs by MTT assay.
|
41066447 |
| NCI-H226 | IC50 |
57.0 nM
|
Antiproliferative activity against human NCI-H226 lung cancer cells assessed as reduction in cell viability incubated for 72 hrs by MTT assay.
Antiproliferative activity against human NCI-H226 lung cancer cells assessed as reduction in cell viability incubated for 72 hrs by MTT assay.
|
41066447 |
| NALM-6 | IC50 |
23.4 nM
|
Antiproliferative activity against human NALM6 B cell acute lymphoblastic leukemia cells assessed as reduction in cell viability incubated for 72 hrs by MTT assay.
Antiproliferative activity against human NALM6 B cell acute lymphoblastic leukemia cells assessed as reduction in cell viability incubated for 72 hrs by MTT assay.
|
41066447 |
| SJSA-1 | IC50 |
174.2 nM
|
Antiproliferative activity against human SJSA-1 osteosarcoma cells assessed as reduction in cell viability incubated for 72 hrs by MTT assay.
Antiproliferative activity against human SJSA-1 osteosarcoma cells assessed as reduction in cell viability incubated for 72 hrs by MTT assay.
|
41066447 |
| U-87MG ATCC | IC50 |
33.9 nM
|
Antiproliferative activity against human U87 glioblastoma cells assessed as reduction in cell viability incubated for 72 hrs by MTT assay.
Antiproliferative activity against human U87 glioblastoma cells assessed as reduction in cell viability incubated for 72 hrs by MTT assay.
|
41066447 |
| SK-UT-1 | IC50 |
106.3 nM
|
Antiproliferative activity against human SKUT1 uterine leiomyosarcoma cells assessed as reduction in cell viability incubated for 72 hrs by MTT assay.
Antiproliferative activity against human SKUT1 uterine leiomyosarcoma cells assessed as reduction in cell viability incubated for 72 hrs by MTT assay.
|
41066447 |
| REH | IC50 |
6.6 nM
|
Antiproliferative activity against human REH acute lymphocytic leukemia cells assessed as reduction in cell viability incubated for 72 hrs by MTT assay.
Antiproliferative activity against human REH acute lymphocytic leukemia cells assessed as reduction in cell viability incubated for 72 hrs by MTT assay.
|
41066447 |
In Vitro
dCDK9-202 (compound 14) (0.25-25 nM; 2-24 h) potently and selectively degrades CDK9 in TC-71 Ewing sarcoma cells via a proteasome-dependent CRBN-mediated mechanism, with a DC50 of 3.5 nM, and achieves nearly complete degradation within 8 h at a concentration of 10 nM[1].
dCDK9-202 (0.25-25 nM; 6 h) potently degrades CDK9 in U87 glioblastoma cells, SKUT1 uterine leiomyosarcoma cells and RH5 rhabdomyosarcoma cells, with a DC50 value of less than 10 nM[1].
dCDK9-202 (72 h) potently inhibits the growth of various human cancer cell lines derived from different tissues, with IC50 values ranging from 2.4 nM (RH5 rhabdomyosarcoma) to 174.2 nM (SJSA-1 osteosarcoma)[1].
dCDK9-202 (10 nM; 0-24 h) selectively degrades CDK9 in TC-71 Ewing sarcoma cells within 8 h, without inducing acute off-target degradation of IKZF1/3 or other CDK family members[1].
dCDK9-202 (0.25-25 nM; 6-8 h) impairs Pol2 activity and disrupts the oncogenic transcriptome in TC-71 Ewing sarcoma cells, reduces Pol2 phosphorylation levels, inhibits key oncoproteins and anti-apoptotic proteins, and suppresses pro-tumor signaling pathways[1].
dCDK9-202 (10-50 nM; 24 h) inhibits DNA replication and induces apoptosis in TC-71 Ewing sarcoma cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Cell Line:TC-71 Ewing sarcoma cells
-
Concentration:10 nM (time-course)
0.25 nM, 2.5 nM, 25 nM (6 h treatment)
20 nM (inhibitor pre-treatment) -
Incubation Time:2 h, 4 h, 8 h, 12 h, 24 h (10 nM time-course)
6 h (0.25-25 nM treatment)
4 h (20 nM treatment, preceded by 2 h pre-treatment) -
Result:Achieved near-complete CDK9 degradation within 8 h of 10 nM treatment, with durable degradation maintained through 24 h.
Efficiently depleted CDK9 protein at concentrations as low as 0.25 nM after 6 h treatment.
Blocked CDK9 degradation by pre-treatment with 10 μM cyclin-dependent kinase inhibitor SNS032 (HY-10008), 10 μM immunomodulatory imide drug thalidomide, 5 μM (R)-MG132 (HY-13259C) proteasome inhibitor, or 2 μM NEDD8-activating enzyme inhibitor MLN4924 (HY-70062).
-
Cell Line:U87 glioblastoma, SKUT1 uterine leiomyosarcoma, and RH5 rhabdomyosarcoma cells
-
Concentration:0.25 nM, 2.5 nM, 25 nM
-
Incubation Time:6 h
-
Result:Significantly depleted endogenous CDK9 at all tested concentrations in U87, SKUT1, and RH5 cells, with DC50 values below 10 nM in all three cell lines.
-
Cell Line:TC-71 Ewing sarcoma cells
-
Concentration:10, 50 nM
-
Incubation Time:24 h
-
Result:Inhibited DNA replication and induces apoptosis in TC-71 Ewing sarcoma cells, with near-complete CDK9 depletion and elevated apoptotic markers observed after 24 h treatment at 50 nM.
-
Cell Line:TC-71 Ewing sarcoma cells
-
Concentration:10 nM
-
Incubation Time:0 h, 2 h, 4 h, 8 h, 12 h, 24 h
-
Result:Induced selective degradation of CDK9 within 8 h, with no acute depletion of IKZF1/3.
Downregulated CDK4/5/6/8/11 and IKZF3 after 12 h, indicating a secondary effect.
Parmacokinetics
| Species | Dose | Route | T1/2 | Cmax | AUC0-t | CL | Vss |
|---|---|---|---|---|---|---|---|
| Mice[1] | 2 mg/kg | i.v. | 0.3 h | 280 ng/mL | 116 ng·h/mL | 312 mL/min/kg | 7.1 L/kg |
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Animal Model:NCG (NOD/ShiLtJGpt-Prkdcem26Cd52Il2rgem26Cd22/Gpt) mice (female, 6 to 8 weeks old, subcutaneous xenograft model, One million TC-71 cells were mixed with 100 μL of PBS/Matrigel solution (1:1) and implanted subcutaneously into the dorsal flank of
recipient mice)[1] -
Dosage:10 mg/kg
-
Administration:i.v.; every other day for 7 doses; single dose (PD testing)
-
Result:Significantly reduced TC-71 xenograft tumor volume and tumor weight over a 12-day treatment period.
Reduced intratumoral CDK9 protein levels within 2 hours following a single dose.
Reduced spleen CDK9 protein levels within 2 hours following a single dose, with levels returning by 6 hours.
Caused no body weight loss in treated mice.
Chemical Information
-
Appearance Solid
-
Peso molecular 803.99
-
Fòrmula C40H49N7O7S2
-
Color White to off-white
-
SMILES
CC(C)(C1=CN=C(O1)CSC2=CN=C(S2)NC(C3CCN(CC3)C(CCCCCCCN4CC5=C(C4)C=C6C(N(C(C6=C5)=O)C7CCC(NC7=O)=O)=O)=O)=O)C
-
Envío
Room temperature in continental US; may vary elsewhere.
-
Almacenamiento
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvente y solubilidad
In Vitro:
DMSO : 100 mg/mL (124.38 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 (3.11 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 (3.11 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.
Pureza y Documentación
-
Ficha de datos (280 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)
-
Instrucciones de manejo (2659 KB)
Referencias
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 | 1.2438 mL | 6.2190 mL | 12.4380 mL | 31.0949 mL |
| 5 mM | 0.2488 mL | 1.2438 mL | 2.4876 mL | 6.2190 mL | |
| 10 mM | 0.1244 mL | 0.6219 mL | 1.2438 mL | 3.1095 mL | |
| 15 mM | 0.0829 mL | 0.4146 mL | 0.8292 mL | 2.0730 mL | |
| 20 mM | 0.0622 mL | 0.3109 mL | 0.6219 mL | 1.5547 mL | |
| 25 mM | 0.0498 mL | 0.2488 mL | 0.4975 mL | 1.2438 mL | |
| 30 mM | 0.0415 mL | 0.2073 mL | 0.4146 mL | 1.0365 mL | |
| 40 mM | 0.0311 mL | 0.1555 mL | 0.3109 mL | 0.7774 mL | |
| 50 mM | 0.0249 mL | 0.1244 mL | 0.2488 mL | 0.6219 mL | |
| 60 mM | 0.0207 mL | 0.1036 mL | 0.2073 mL | 0.5182 mL | |
| 80 mM | 0.0155 mL | 0.0777 mL | 0.1555 mL | 0.3887 mL | |
| 100 mM | 0.0124 mL | 0.0622 mL | 0.1244 mL | 0.3109 mL |
dCDK9-202 Related Classifications
HY-178861 Related Classifications
Powered by Bioz