Cat. No.: HY-170978

PROTAC CDK9 degrader-11

PROTAC CDK9 degrader-11 is an orally active, selective CDK9 PROTAC degrader with a DC₅₀ of 1.09 nM. PROTAC CDK9 degrader-11 recruits CRBN to form a ternary complex and degrades CDK9 via the ubiquitin-proteasome pathway, thereby inhibiting RNA polymerase II phosphorylation and downregulating the expression of anti-apoptotic and pro-oncogenic genes, ultimately inducing apoptosis. PROTAC CDK9 degrader-11 is suitable for research on small-cell lung cancer (SCLC).
(Pink: CDK9 ligand (HY-170979); Blue: Cereblon ligand (HY-W247437); Black: linker).

For research use only. We do not sell to patients.

CAS No.: 3039540-19-4
Formula: C₃₉H₄₈Cl₂N₁₀O₅
Molecular Weight:807.77

Storage:

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

Data Sheet (284 KB)

PROTAC CDK9 degrader-11 Chemical Structure

CAS No.: 3039540-19-4

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Top Publications Citing

Use of MCE Products

Fluorescent Dye

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

Biological Activity
- Description
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- Parmacokinetics
- In Vivo
Chemical Information
Purity & Documentation
References
Calculators
Help & FAQs
Classifications
Bioz

Biological Activity

Description

PROTAC CDK9 degrader-11 is an orally active, selective CDK9 PROTAC degrader with a DC₅₀ of 1.09 nM. PROTAC CDK9 degrader-11 recruits CRBN to form a ternary complex and degrades CDK9 via the ubiquitin-proteasome pathway, thereby inhibiting RNA polymerase II phosphorylation and downregulating the expression of anti-apoptotic and pro-oncogenic genes, ultimately inducing apoptosis. PROTAC CDK9 degrader-11 is suitable for research on small-cell lung cancer (SCLC)^[1]. (Pink: CDK9 ligand (HY-170979); Blue: Cereblon ligand (HY-W247437); Black: linker).

IC₅₀ & Target^[1]

CDK9

1.09 nM (DC₅₀)

PARP-1

Caspase 3

All PROTACs Isoforms :

All CDK Isoforms :

All DNA/RNA Synthesis Isoforms :

All PARP Isoforms :

All Caspase Isoforms :

Cellular Effect

Cell Line	Type	Value	Description	References
NCI-H69	IC₅₀	1.027 mM	Significantly inhibits cell viability. Significantly inhibits cell viability.	39895086
NCI-H446	IC₅₀	1.008 nM	Significantly inhibits cell viability. Significantly inhibits cell viability.	39895086
BEAS-2B	IC₅₀	412.8 nM	Does not affect cell viability. Does not affect cell viability.	39895086
L02	IC₅₀	69.94 nM	Does not affect cell viability. Does not affect cell viability.	39895086
HEK-293T	IC₅₀	95.47 nM	Does not affect cell viability. Does not affect cell viability.	39895086

In Vitro

PROTAC CDK9 degrader-11 (Compound C3) (0.5-10.0 nM; 8 h) induces the degradation of CDK9 protein in a concentration-dependent manner in NCI-H69 and NCI-H446 cells^[1].
PROTAC CDK9 degrader-11 (10 nM; 0.5-12 h) induces the time-dependent degradation of CDK9 protein and promotes CDK9 ubiquitination in NCI-H69 and NCI-H446 cells^[1].
PROTAC CDK9 degrader-11 (0.5-10.0 nM; 24 h) inhibits RNA Pol II phosphorylation (at Ser2 and Ser5 sites) and downregulates c-Myc protein expression in NCI-H69 cells^[1].
PROTAC CDK9 degrader-11 (1 pM-10 μM; 72 h) significantly inhibits cell viability in NCI-H69 (IC₅₀ = 1.027 nM), NCI-H146, NCI-H446 (IC₅₀ = 1.008 nM), NCI-H524, and DMS114 cells, while showing lower cytotoxicity in normal cells such as MCF10A (IC₅₀ = 126.3 nM), Beas-2b (IC₅₀ = 412.8 nM), LO2 (IC₅₀ = 69.94 nM), and 293T (IC₅₀ = 95.47 nM)^[1].
PROTAC CDK9 degrader-11 (2-4 nM; 8-21 days) inhibits colony formation in NCI-H69, NCI-H446, and DMS114 cells^[1].
PROTAC CDK9 degrader-11 (0.5-4 nM; 36 h) induces cell cycle arrest at the G0/G1 phase and apoptosis in NCI-H69 and NCI-H446 cells^[1].
PROTAC CDK9 degrader-11 (0.5-5.0 nM; 36 h) downregulates the expression of MCL-1 and BCL-2 and upregulates the expression of Cleaved-PARP and Cleaved-Caspase-3 in NCI-H69 cells^[1].
PROTAC CDK9 degrader-11 (2-4 nM; 48 h) inhibits cell invasion in DMS114 and DMS53 cells^[1].
PROTAC CDK9 degrader-11 (0.3-30 μM; 18 h) demonstrates a low risk of cardiotoxicity (IC₅₀ > 30 μM) in an in vitro hERG binding assay using HEK-293 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-H69, NCI-H446
Concentration:

0.5, 1.0, 2.5, 5.0, 7.5, 10.0 nM
Incubation Time:

8 h
Result:

Decreased CDK9 protein levels in a dose-dependent manner.

Western Blot Analysis^[1]

Cell Line:

NCI-H69, NCI-H446
Concentration:

10 nM
Incubation Time:

0.5, 1, 3, 6, 12 h
Result:

Decreased CDK9 protein levels in a time-dependent manner.

Western Blot Analysis^[1]

Cell Line:

NCI-H69, NCI-H446
Concentration:

0.5, 1.0, 2.5, 5.0, 7.5, 10.0 nM
Incubation Time:

3 h
Result:

Significantly increased the ubiquitination levels of CDK9 protein.

Western Blot Analysis^[1]

Cell Line:

NCI-H69
Concentration:

0.5, 1.0, 2.5, 5.0, 7.5, 10.0 nM
Incubation Time:

24 h
Result:

Decreased the phosphorylation levels of RNA Pol II (Ser2 and Ser5) in a dose-dependent manner.

Western Blot Analysis^[1]

Cell Line:

NCI-H69
Concentration:

2.5, 5, 10 nM
Incubation Time:

24 h
Result:

Decreased the expression of c-Myc protein in a dose-dependent manner.

Cell Viability Assay^[1]

Cell Line:

NCI-H69, NCI-H146, NCI-H446, NCI-H524, DMS114
Concentration:

1 pM, 10 pM, 100 pM, 1 nM, 10 nM, 100 nM, 1 μM, 10 μM
Incubation Time:

72 h
Result:

Significantly decreased cell viability.

Cell Proliferation Assay^[1]

Cell Line:

NCI-H69, NCI-H446, DMS114
Concentration:

2, 4 nM
Incubation Time:

8 to 21 days
Result:

Significantly decreased the number of malignant colonies formed.

Cell Cycle Analysis^[1]

Cell Line:

NCI-H69, NCI-H446
Concentration:

0.5, 1, 2, 4 nM
Incubation Time:

36 h
Result:

Increased the proportion of cells in the G1 phase in a dose-dependent manner.

Apoptosis Analysis^[1]

Cell Line:

NCI-H69, NCI-H446
Concentration:

1, 2, 4 nM
Incubation Time:

36 h
Result:

Increased cell apoptosis rates in a dose-dependent manner.

Western Blot Analysis^[1]

Cell Line:

NCI-H69
Concentration:

0.5, 1.0, 2.5, 5.0 nM
Incubation Time:

36 h
Result:

Upregulated the expression of pro-apoptotic proteins (Cleaved-PARP, Cleaved-Caspase-3) and downregulated anti-apoptotic proteins (MCL-1, BCL-2).

Cell Invasion Assay^[1]

Cell Line:

DMS114, DMS53
Concentration:

2, 4 nM
Incubation Time:

48 h
Result:

Significantly decreased the number of invading cells migrating through the upper chamber.

Cell Viability Assay^[1]

Cell Line:

MCF10A, Beas-2b, LO2, 293T
Concentration:

100 nM, 1 μM, 10 μM, 100 μM
Incubation Time:

72 h
Result:

Normal cell viability was less affected, exhibiting low cytotoxicity.

Parmacokinetics

Species	Dose	Route	T_1/2	C_max	AUC_0-24	AUC_0-∞	F
Mice	25 mg/kg	p.o.	4.7 h	277 ng/mL	951 ng·h/mL	977 ng·h/mL	6.8 %
Mice	5 mg/kg	i.v.	8.2 h	2603 ng/mL	2660 ng·h/mL	2857 ng·h/mL	/
Rat	25 mg/kg	p.o.	5.4 h	179 ng/mL	714 ng·h/mL	893 ng·h/mL	6.5 %
Rat	5 mg/kg	i.v.	2.8 h	2003 ng/mL	2179 ng·h/mL	2331 ng·h/mL	/

In Vivo

PROTAC CDK9 degrader-11 (Compound C3) (12.5 mg/kg or 25.0 mg/kg; p.o.; once daily; 14 days) significantly inhibited tumor growth, reduced CDK9 and Ki-67 expression, and increased Cleaved-caspase-3 expression in a subcutaneous NCI-H446 xenograft BALB/c nude mouse model^[1].
PROTAC CDK9 degrader-11 (12.5 mg/kg or 25.0 mg/kg; p.o.; once daily; 19 days) significantly reduced systemic metastasis and overall tumor burden in a BALB/c nude mouse model with systemic metastasis induced by tail vein injection of NCI-H446-Luc-GFP cells^[1].
PROTAC CDK9 degrader-11 (12.5 mg/kg or 25.0 mg/kg; p.o.; once daily; 7 days) demonstrated significant inhibition of primary tumor growth in a small-cell lung cancer Mini-PDX model^[1].

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

Animal Model:

BALB/c nude mice (female, 6-week-old) were subcutaneously injected with 5 x 10 ⁶ NCI-H446 cells^[1]
Dosage:

12.5 mg/kg and 25.0 mg/kg
Administration:

p.o.; once daily; for 14 days
Result:

Significantly decreased tumor volume and weight, exhibiting dose-dependent tumor growth inhibitory activity.
Animal body weight remained stable throughout the administration period, and no obvious toxic side effects were observed.
Significantly decreased the expression levels of CDK9 and the proliferation marker Ki-67, while the expression level of the apoptosis marker Cleaved-caspase-3 significantly increased.

Animal Model:

BALB/c nude mice (6-week-old) were injected via the tail vein with 5 x 10 ⁶ NCI-H446-Luc-GFP cells^[1]
Dosage:

12.5 mg/kg and 25.0 mg/kg
Administration:

p.o.; once daily; for 19 days
Result:

Significantly attenuated the fluorescence signal intensity in vivo, as demonstrated by in vivo imaging.
Significantly decreased systemic metastasis and overall tumor burden.
There was no significant difference in body weight changes among the groups of mice.

Animal Model:

BALB/c nude mice (four-week-old, 15-20 g) were used to establish the model by subcutaneously implanting capsules with primary small-cell lung cancer (three capsules per mouse; capsules were washed with HBSS) ^[1]
Dosage:

12.5 mg/kg and 25.0 mg/kg
Administration:

p.o.; once daily; for 7 days
Result:

Significantly reduced the relative fluorescence units (RFU) within capsules containing primary samples.
Demonstrated significant tumor growth inhibition across all tested sample models.

Chemical Information

CAS No. 3039540-19-4
Molecular Weight 807.77
Formula C₃₉H₄₈Cl₂N₁₀O₅
SMILES

O=C(NC1=CNN=C1C(NC2CCN(CC2)C(CN3CCC(CC3)CN4CCN(CC4)C5=CC(NC6C(NC(CC6)=O)=O)=CC=C5)=O)=O)C7=C(C=CC=C7Cl)Cl
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

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

Purity & Documentation

Select Batch:

Purity: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (284 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)

References

[1]. Wang Y, et al., Identification of a Potent and Selective CDK9 Degrader as a Targeted Therapeutic Option for the Treatment of Small-Cell Lung Cancer. J Med Chem. 2025 Feb 13;68(3):2528-2550. [Content Brief]

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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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PROTAC CDK9 degrader-11

All PROTACs Isoforms

All CDK Isoforms

All DNA/RNA Synthesis Isoforms

All PARP Isoforms

All Caspase Isoforms

Biological Activity

Chemical Information

Purity & Documentation

References

Calculators

Help & FAQs

PROTAC CDK9 degrader-11 Related Classifications

HY-170978 Related Classifications

Bioz