Art. -Nr.: HY-188423

dCDK9-010

dCDK9-010 is a potent and selective PROTAC degrader of the CDK9/cyclin T complex (P-TEFb), with DC₅₀ values of 0.5 μM (NCI-H226) and 1.4 μM (TC-32), respectively. dCDK9-010 specifically induces proteasome-dependent degradation of the P-TEFb complex (comprising CDK9 and Cyclin T1/T2a/T2b) by recruiting the MDM2 E3 ubiquitin ligase, thereby blocking RNA Pol II CTD phosphorylation to inhibit transcriptional elongation; meanwhile, through competitive occupancy, it blocks MDM2-mediated ubiquitination and degradation of p53, stabilizing p53 tumor suppressor protein levels. dCDK9-010 inhibits tumor cell proliferation and activates Caspase-3/7 activity, thereby inducing apoptosis. dCDK9-010 can be used for research on non-small cell lung cancer and Ewing sarcoma.
(Pink: CDK9/cyclinT1 ligand (HY-10008); Blue: MDM2 ligand (HY-15676); Black: linker (HY-W040165)).

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Formel: C₅₇H₆₈Cl₂F₂N₈O₉S₂
Molecular Weight:1182.23

Speicherung:

Please store the product under the recommended conditions in the Certificate of Analysis.

Data Sheet (285 KB)

dCDK9-010 Chemical Structure

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Use of MCE Products

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biologische Aktivität
- Beschreibung
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- Parmacokinetics
- In Vivo
Chemical Information
Reinheit & Dokumentation
Verweise
Calculators
Help & FAQs
Classifications
Bioz

Biologische Aktivität

Beschreibung

dCDK9-010 is a potent and selective PROTAC degrader of the CDK9/cyclin T complex (P-TEFb), with DC₅₀ values of 0.5 μM (NCI-H226) and 1.4 μM (TC-32), respectively. dCDK9-010 specifically induces proteasome-dependent degradation of the P-TEFb complex (comprising CDK9 and Cyclin T1/T2a/T2b) by recruiting the MDM2 E3 ubiquitin ligase, thereby blocking RNA Pol II CTD phosphorylation to inhibit transcriptional elongation; meanwhile, through competitive occupancy, it blocks MDM2-mediated ubiquitination and degradation of p53, stabilizing p53 tumor suppressor protein levels. dCDK9-010 inhibits tumor cell proliferation and activates Caspase-3/7 activity, thereby inducing apoptosis. dCDK9-010 can be used for research on non-small cell lung cancer and Ewing sarcoma^[1]. (Pink: CDK9/cyclinT1 ligand (HY-10008); Blue: MDM2 ligand (HY-15676); Black: linker (HY-W040165)).

IC₅₀ & Target

^[1]

CDK9/cycT

0.5 μM (DC₅₀)

CDK9/cycT

1.4 μM (DC₅₀)

Caspase-3

PARP

MDM2

RNA Polymerase

Alle PROTACs Isoform-spezifische Produkte anzeigen :

Alle CDK Isoform-spezifische Produkte anzeigen :

Alle DNA/RNA Synthesis Isoform-spezifische Produkte anzeigen :

Alle Caspase Isoform-spezifische Produkte anzeigen :

Alle PARP Isoform-spezifische Produkte anzeigen :

Cellular Effect

Cell Line	Type	Value	Description	References
NCI-H226	IC₅₀	0.2 μM	Antiproliferative activity against human NCI-H226 cells assessed as viability reduction incubated 72 hrs by MTT assay. Antiproliferative activity against human NCI-H226 cells assessed as viability reduction incubated 72 hrs by MTT assay.	41970231
TC-32	IC₅₀	0.4 μM	Antiproliferative activity against human TC-32 cells assessed as viability reduction incubated 72 hrs by MTT assay. Antiproliferative activity against human TC-32 cells assessed as viability reduction incubated 72 hrs by MTT assay.	41970231
HCT-116	IC₅₀	179.3 nM	Antiproliferative activity against human HCT116 cells assessed as viability reduction incubated 72 hrs by MTT assay. Antiproliferative activity against human HCT116 cells assessed as viability reduction incubated 72 hrs by MTT assay.	41970231
A549	IC₅₀	768.2 nM	Antiproliferative activity against human A549 cells assessed as viability reduction incubated 72 hrs by MTT assay. Antiproliferative activity against human A549 cells assessed as viability reduction incubated 72 hrs by MTT assay.	41970231
NALM-6	IC₅₀	357.0 nM	Antiproliferative activity against human NALM6 cells assessed as viability reduction incubated 72 hrs by MTT assay. Antiproliferative activity against human NALM6 cells assessed as viability reduction incubated 72 hrs by MTT assay.	41970231
MKN-45	IC₅₀	2286.0 nM	Antiproliferative activity against human MKN45 cells assessed as viability reduction incubated 72 hrs by MTT assay. Antiproliferative activity against human MKN45 cells assessed as viability reduction incubated 72 hrs by MTT assay.	41970231
HepG2	IC₅₀	1052.7 nM	Antiproliferative activity against human HEPG2 cells assessed as viability reduction incubated 72 hrs by MTT assay. Antiproliferative activity against human HEPG2 cells assessed as viability reduction incubated 72 hrs by MTT assay.	41970231
REH	IC₅₀	461.4 nM	Antiproliferative activity against human REH cells assessed as viability reduction incubated 72 hrs by MTT assay. Antiproliferative activity against human REH cells assessed as viability reduction incubated 72 hrs by MTT assay.	41970231
HT-1080	IC₅₀	185.3 nM	Antiproliferative activity against human HT1080 cells assessed as viability reduction incubated 72 hrs by MTT assay. Antiproliferative activity against human HT1080 cells assessed as viability reduction incubated 72 hrs by MTT assay.	41970231
U-251	IC₅₀	> 10000 nM	Antiproliferative activity against human U251 cells assessed as viability reduction incubated 72 hrs by MTT assay with IC50 greater than 10,000 nM. Antiproliferative activity against human U251 cells assessed as viability reduction incubated 72 hrs by MTT assay with IC50 greater than 10,000 nM.	41970231
NCI-H1299	IC₅₀	> 10000 nM	Antiproliferative activity against human NCI-H1299 cells assessed as viability reduction incubated 72 hrs by MTT assay with IC50 greater than 10,000 nM. Antiproliferative activity against human NCI-H1299 cells assessed as viability reduction incubated 72 hrs by MTT assay with IC50 greater than 10,000 nM.	41970231
THP-1	IC₅₀	> 10 μM	Antiproliferative activity against human THP-1 cells assessed as viability reduction incubated 72 hrs by MTT assay with IC50 greater than 10 μM. Antiproliferative activity against human THP-1 cells assessed as viability reduction incubated 72 hrs by MTT assay with IC50 greater than 10 μM.	41970231
DLD-1	IC₅₀	>10 μM	Antiproliferative activity against human DLD-1 cells assessed as viability reduction incubated 72 hrs by MTT assay with IC50 greater than 10 μM. Antiproliferative activity against human DLD-1 cells assessed as viability reduction incubated 72 hrs by MTT assay with IC50 greater than 10 μM.	41970231
MDA-MB-231	IC₅₀	> 10 μM	Antiproliferative activity against human MDA-MB-231 cells assessed as viability reduction incubated 72 hrs by MTT assay with IC50 greater than 10 μM. Antiproliferative activity against human MDA-MB-231 cells assessed as viability reduction incubated 72 hrs by MTT assay with IC50 greater than 10 μM.	41970231

In Vitro

Anti-cancerApoptosisCell Cycle RegulationOthers

Anti-cancer

dCDK9-010 induces CDK9 degradation in NCI-H226 and TC-32 cells, with DC₅₀ values of 0.5 μM and 1.4 μM, respectively^[1].
dCDK9-010 (2 μM; 8 h) degrades the CDK9/Cyclin T complex in NCI-H226 and TC-32 cells in an MDM2- and proteasome pathway-dependent manner^[1].
dCDK9-010 (72 h) has submicromolar activity in NCI-H226 and TC-32 cells, with IC₅₀ values of 0.2 μM and 0.4 μM, respectively^[1].
dCDK9-010 (2 μM; 4-24 h) induces degradation of CDK9 and Cyclin T isoforms (T1, T2a, T2b), inhibits Rpb1 CTD Ser2 phosphorylation, and upregulates MDM2, p53, and p21 protein levels in NCI-H226 and TC-32 cells^[1].
dCDK9-010 (72 h) induces cell death and inhibits cell viability in TC-32 and NCI-H226 cells in a manner dependent on wild-type MDM2 and p53^[1].
dCDK9-010 (0.125-2 μM; 24 h) selectively degrades the CDK9/Cyclin T complex, inhibits Rpb1 phosphorylation, and activates the p53 pathway in TP53 wild-type HCT116, HT1080, NCI-H460, and U87 cells^[1].
dCDK9-010 (0.001-10 μM; 72 h) exhibits submicromolar antiproliferative activity in multiple TP53 wild-type cancer cell lines, with IC₅₀ values ranging from 171.7 to 2188.3 nM^[1].

Anti-cancer

Apoptosis

dCDK9-010 (500 nM; 24 h) induces PARP cleavage (c-PARP) and triggers apoptosis in TC-32 cells^[1].
dCDK9-010 (0.5-2 μM; 24 h) induces caspase-dependent apoptosis in NCI-H226 and TC-32 cells^[1].
dCDK9-010 (0.5-2 μM; 24 h) significantly inhibits cellular DNA replication (BrdU incorporation) and proliferation, and activates Caspase-3/7 activity and induces the expression of apoptosis markers (c-PARP, cleaved Caspase-3) in TC-32 and NCI-H226 cells^[1].

Anti-cancer

Cell Cycle Regulation

dCDK9-010 (2 μM; 4-24 h) has the effect of inducing downregulation of CDK2 and other CDKs (CDK4, 6, 11, 12, 13) protein and mRNA levels in NCI-H226 and TC-32 cells^[1].
dCDK9-010 (500 nM; 8 h) significantly upregulates p53 pathway gene expression and inhibits the expression of genes related to the mitotic spindle and G2/M checkpoint pathways in NCI-H226 and TC-32 cells^[1].

Others

dCDK9-010 (0.5-2 μM; 24 h) exhibits very low toxicity and weak degradation effects in TP53-mutant or -deficient HEK293T and ASC52telo non-malignant cells, demonstrating a favorable safety profile^[1].
dCDK9-010 (500 nM; 8 h) significantly attenuates the EWS-FLI1-dependent transcriptional network in TC-32 cells^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Western Blot Analysis^[1]

Cell Line:

NCI-H226 and TC-32 cells
Concentration:

2 μM
Incubation Time:

4, 8, 12, and 24 h
Result:

Rapidly reduced the protein levels of CDK9 (CDK9-L and CDK9-S) and Cyclin T2, followed by the depletion of Cyclin T1.
Decreased the phosphorylation of Rpb1 CTD Ser2 and significantly elevated the protein expression levels of MDM2, p53, and p21.

Western Blot Analysis^[1]

Cell Line:

NCI-H226 and TC-32 cells
Concentration:

2 μM
Incubation Time:

4, 8, 12, and 24 h
Result:

Indirectly reduced the protein levels of other CDKs (including CDK2, CDK4, CDK6, CDK11, CDK12, and CDK13) after 24 hours of treatment.

Real Time qPCR^[1]

Cell Line:

NCI-H226 cells
Concentration:

2 μM
Incubation Time:

8 h, 24 h
Result:

Significantly downregulated the mRNA levels of CDK2, CDK4, CDK6, CDK11, CDK12, and CDK13, and this downregulation preceded their protein reduction.

Cell Viability Assay^[1]

Cell Line:

TC-32 and NCI-H226 (wild-type and MDM2/TP53 cells
Concentration:

0.001 μM, 0.01 μM, 0.1 μM, 1 μM, 10 μM
Incubation Time:

72 h
Result:

Significantly inhibited the proliferation of wild-type cancer cells; whereas in cells with MDM2 or TP53 knockdown or knockout, the anti-proliferative activity of dCDK9-010 was significantly attenuated or completely resisted.

Western Blot Analysis^[1]

Cell Line:

HCT116, HT1080, NCI-H460, U87, HEK293T, ASC52telo cells
Concentration:

0.125 μM, 0.5 μM, 2 μM
Incubation Time:

24 h
Result:

Dose-dependently reduced the protein levels of CDK9 and Cyclin T, downregulated Rpb1 CTD Ser2 phosphorylation, and increased p53 and p21 expression in TP53 wild-type cancer cells; conversely, dCDK9-010 exhibited minimal degradation effects in HEK293T and ASC52telo cells.

Cell Proliferation Assay^[1]

Cell Line:

NCI-H226 and TC-32 cells
Concentration:

0.5 μM, 2 μM
Incubation Time:

24 h
Result:

Profoundly suppressed cellular DNA replication and significantly reduced the BrdU incorporation rate.

Parmacokinetics

Species	Dose	Route	T_1/2	C_max	AUC_0-t	Bioavailability	CL	V_z
Mice^[1]	2 mg/kg	i.v.	5.6 h	/	11694 ng·h/mL	/	2.9 mL/min/kg	1.4 L/kg
Mice^[1]	10 mg/kg	i.p.	5.9 h	6653 ng/mL	31187 ng·h/mL	55 %	/	/

In Vivo

Anti-cancer

dCDK9-010 (20 mg/kg; i.v.; once every other day) significantly inhibits tumor growth and reduces tumor volume and weight in the NCI-H226 subcutaneous xenograft tumor model established in immunodeficient NCG mice, and induces degradation of CDK9 and Cyclin T in tumor tissue without significantly affecting mouse body weight^[1].
dCDK9-010 (20 mg/kg; i.v.; once every other day; 12 days) significantly inhibits tumor growth and reduces tumor volume and weight in the TC-32 subcutaneous xenograft tumor model established in immunodeficient NCG mice, without causing significant mouse body weight loss^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:

NCG (NOD/ShiLtJGpt-*Prkdc^em26Cd52 Il2rg^em26Cd22*/Gpt; female; 6-8 weeks old)^[1]
Dosage:

20 mg/kg
Administration:

i.v.; once every other day; 12 days
Result:

Significantly inhibited xenograft tumor growth.
Reduced xenograft volume and weight.
Did not cause significant mouse body weight loss.

Related Protocols :

Chemical Information

Molecular Weight 1182.23
Formel C₅₇H₆₈Cl₂F₂N₈O₉S₂
SMILES

O=C(C1CCN(C(CCOCCOCCOCCNC(C2=CC=C(NC([C@@H]3N[C@@H](CC(C)(C)C)[C@](C#N)(C4=CC=C(Cl)C=C4F)[C@H]3C5=CC=CC(Cl)=C5F)=O)C(OC)=C2)=O)=O)CC1)NC6=NC=C(SCC7=NC=C(C(C)(C)C)O7)S6
Versand

Room temperature in continental US; may vary elsewhere.
Speicherung

Please store the product under the recommended conditions in the Certificate of Analysis.

Reinheit & Dokumentation

Select Batch:

Reinheit: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (285 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

Verweise

[1]. Guan X, et al. Discovery of a First-in-Class Murine Double Minute 2-Recruiting Positive Transcription Elongation Factor B PROTAC Degrader With Selective Antitumor Activity. MedComm (2020). 2026 Apr 9;7(4):e70723.

Calculators

Molaritätsrechner

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

Konzentration Konzentration

Volumen Volumen

Molecular Weight Molecular Weight

Verdünnungsrechner

Konzentration _{(Stammlösung)} × Volumen _{(Stammlösung)} = Konzentration _{(Ziellösung)} × Volumen _{(Ziellösung)}

Konzentration _{(Stammlösung)} Konzentration _{(Stammlösung)}

Volumen _{(Stammlösung)} Volumen _{(Stammlösung)}

Konzentration _{(Ziellösung)} Konzentration _{(Ziellösung)}

Volumen _{(Ziellösung)} Volumen _{(Ziellösung)}

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

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dCDK9-010

Alle PROTACs Isoform-spezifische Produkte anzeigen

Alle CDK Isoform-spezifische Produkte anzeigen

Alle DNA/RNA Synthesis Isoform-spezifische Produkte anzeigen

Alle Caspase Isoform-spezifische Produkte anzeigen

Alle PARP Isoform-spezifische Produkte anzeigen