PROTAC CDK9 degrader-13
PROTAC CDK9 degrader-13 is a selective CDK9 degrader acting via the ubiquitin-proteasome system. PROTAC CDK9 degrader-13 induces apoptosis in acute myeloid leukemia cells. PROTAC CDK9 degrader-13 suppresses tumor growth in vivo and has a defined safety profile. PROTAC CDK9 degrader-13 can be used for the research of acute myeloid leukemia.
(Pink: CDK9 ligand (HY-184694); Blue: Cereblon ligand (HY-41547); Black: linker (HY-184695)).
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- 화학식: C45H58Cl2N8O9
- 분자량:925.90
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보관:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
- Protocol
- 순도&문서
- References
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Help & FAQs
Biological Activity
제품 설명
IC50 & Target
[1]|
CDK9 |
Caspase 3 |
In Vitro
PROTAC CDK9 degrader-13 (compound D6) (72 h) potently inhibits the proliferation of MV-4-11, MOLM-13, HL-60, THP-1 and HCT116 cells, with the strongest activity against MOLM-13 cells (IC50 = 1.88 μM), and shows no obvious cytotoxicity against MCF-7 and 293T cells[1].
PROTAC CDK9 degrader-13 (1-24 μM; 24 h, 4 μM; 12-48 h) induces time- and concentration-dependent degradation of CDK9 in MOLM-13 cells[1].
PROTAC CDK9 degrader-13 (4 μM; 24-36 h) selectively induces CDK9 degradation in MOLM-13 cells, without causing significant degradation of CDK2, CDK4 or CDK8[1].
PROTAC CDK9 degrader-13 (4-8 μM) induces proteasome-dependent, CRBN ligand-competitive degradation of CDK9 in MOLM-13 cells[1].
PROTAC CDK9 degrader-13 (2-8 μM; 36 h) dose-dependently inhibits the migration of MOLM-13 cells[1].
PROTAC CDK9 degrader-13 (1-4 μM; 36 h) induces apoptosis in MOLM-13 cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MOLM-13
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Concentration:1, 2, 4, 8, 12, 16, 20, 24 μM (24 h incubation)
4 μM (12-48 h incubation) -
Incubation Time:24 h (1-24 μM)
12, 18, 24, 30, 36, 42, 48 h (4 μM) -
Result:Achieved an optimal CDK9 degradation rate of 33% at 4 μM for 24 h.
Achieved a maximal degradation (Dmax) of 45% at 4 μM for 36 h.
Showed reduced degradation efficiency at concentrations above 12 μM at both 24 h and 36 h, likely due to the hook effect.
Showed noticeable CDK9 reduction starting at 24 h, with maximal degradation achieved at 36 h at 4 μM.
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Cell Line:MOLM-13
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Concentration:4 μM
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Incubation Time:24 h, 36 h
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Result:Reduced CDK2 levels by approximately 26% relative to control at 24 h, while reducing CDK9 levels.
Reduced CDK2 degradation to approximately 10% at 36 h, while CDK9 degradation remained stable at approximately 25%.
Showed no notable changes in CDK4 or CDK8 protein levels at either 24 h or 36 h.
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Cell Line:MOLM-13
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Concentration:1, 2, 4 μM (Annexin V-FITC/PI staining)
2 μM (Hoechst 33342 staining)
4 μM (Western blot) -
Incubation Time:36 h
24, 36 h (Western blot) -
Result:Induced condensed and fragmented nuclei (apoptotic morphology) in treated cells via Hoechst 33342 staining.
Induced apoptosis in approximately 20% of the cell population at 4 μM for 36 h via Annexin V-FITC/PI staining.
Reduced Mcl-1 protein levels by 27% and full-length Caspase-3 levels by 37% at 4 μM for 36 h via Western blot analysis.
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Cell Line:MOLM-13
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Concentration:2, 4, 8 μM
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Incubation Time:36 h
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Result:Suppressed chemotactic migration of MOLM-13 cells in a dose-dependent manner.
Achieved an 86% inhibition rate at 8 μM for 36 h.
Parmacokinetics
| Species | Dose | Route | T1/2 (Distribution) | T1/2β | Cmax | AUC0-t | AUC0-∞ | CL |
|---|---|---|---|---|---|---|---|---|
| Mice[1] | 10 mg/kg | i.v. | 0.061 h | 1.069 h | 52.329 mg/L | 17.821 mg·h/L | 25.78 mg·h/L | 0.388 L/h/kg |
In Vivo
PROTAC CDK9 degrader-13 (30-90 mg/kg; i.p.; once daily; for 7 consecutive days) is well tolerated in healthy female BALB/c mice, with no significant body weight loss or organ lesions observed[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c nude mice (female, 5-week-old, ~16 g, subcutaneous xenograft of MOLM-13 cells)[1]
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Dosage:20 mg/kg
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Administration:i.v.; daily; 11 days
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Result:Attained 31% tumor growth suppression.
Lowered tumor volume to 675 mm3 versus 1133 mm3 of saline control.
Suppressed tumor weight by 23% against untreated control.
Evidentiated tumor tissue damage on H&E staining.
Exhibited extensive tumor apoptosis on TUNEL staining.
Produced negligible body weight decline throughout dosing.
Displayed no treatment-triggered visceral pathological lesions.
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Animal Model:BALB/c mice (female, 6-week-old, ~20 g)[1]
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Dosage:30 mg/kg; 60 mg/kg; 90 mg/kg
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Administration:i.p.; daily; 7 days
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Result:Preserved stable body weight at 30 mg/kg across treatment.
Triggered brief early weight loss at 60/90 mg/kg with day 3 recovery.
Confined all-group weight shifts to within 5% baseline.
Displayed normal visceral histology free of necrosis and lesions.
Chemical Information
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분자량 925.90
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화학식 C45H58Cl2N8O9
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SMILES
O=C1N(C(CC2)C(NC2=O)=O)C(C3=C1C=CC=C3NCCCCCCCCCCCCCCCCN4N=NC(COCC5=NC6=CC(Cl)=C(Cl)C=C6N5[C@@H]7O[C@H](CO)[C@@H](O)[C@H]7O)=C4)=O
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Please store the product under the recommended conditions in the Certificate of Analysis.
순도&문서
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
PROTAC CDK9 degrader-13 Related Classifications
HY-184693 Related Classifications
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