2. Epigenetics
  3. Epigenetic Reader Domain
  4. KWZL-7f15

KWZL-7f15 (compound 7f15) is a dual CDK6/BET inhibitor with an IC50 of 31.81 nM against human CDK6. KWZL-7f15 inhibits the CDK6-RB axis and the BRD4-Myc axis. KWZL-7f15 exhibits antiproliferative activity against triple-negative breast cancer cells. KWZL-7f15 shows antitumor activity in xenograft mouse models without significant adverse effects. KWZL-7f15 can be used in studies related to triple-negative breast cancer.

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

KWZL-7f15

KWZL-7f15 Chemical Structure

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KWZL-7f15 Related Antibodies

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Description

KWZL-7f15 (compound 7f15) is a dual CDK6/BET inhibitor with an IC50 of 31.81 nM against human CDK6. KWZL-7f15 inhibits the CDK6-RB axis and the BRD4-Myc axis. KWZL-7f15 exhibits antiproliferative activity against triple-negative breast cancer cells. KWZL-7f15 shows antitumor activity in xenograft mouse models without significant adverse effects. KWZL-7f15 can be used in studies related to triple-negative breast cancer[1].

In Vitro

KWZL-7f15 (compound 7f15) exhibited potent cytotoxicity against triple-negative breast cancer (TNBC) cell lines MDA-MB-231 (IC50 = 0.35 μM), BT-549 (IC50 = 2.77 μM), and showed high selectivity with IC50 > 30 μM against normal mammary epithelial MCF-10A cells[1].
KWZL-7f15 (500 nM for CDK4/CycD1 and CDK6/CycD3) acted as a pan-BET and preferential CDK4/CDK6 inhibitor, with IC50 values of 31.81 nM (CDK6), 56.41 nM (BRD4), 37.30 nM (BRD2 BD1+BD2), 34.02 nM (BRD3 BD1+BD2), 31.79 nM (BRD4 BD2), and showed 57.73% inhibition of CDK4/CycD1 and 80.53% inhibition of CDK6/CycD3 at 500 nM[1].
KWZL-7f15 confirmed direct binding to CDK6 and BRD4 in MDA-MB-231 cells via cellular thermal shift assay, increasing their thermal stability[1].
KWZL-7f15 modulated protein expression in MDA-MB-231 cells, causing dose- and time-dependent downregulation of BRD4, c-Myc, p-Rb, and Bcl2, and upregulation of Bax and cleaved-caspase 3[1].
KWZL-7f15 (0.25-1 μM; 48 h) induced G0/G1 phase arrest in MDA-MB-231 cells in a dose-dependent manner[1].
KWZL-7f15 induced oxidative stress and DNA damage in MDA-MB-231 cells, increasing intracellular ROS levels, elevating γ-H2AX, suppressing RAD51, and inducing DNA strand breaks[1].
KWZL-7f15 (0.25 μM) inhibited cell migration of MDA-MB-231 cells in a wound-healing assay[1].
KWZL-7f15 (0.25 μM) inhibited colony formation of MDA-MB-231 cells[1].
KWZL-7f15 bound to CDK6 (PDB: 5L2S) via insertion of the pyrimidine-NH-pyridine motif into the hinge region and an additional hydrogen bond with ASP104, and bound to BRD4 (PDB: 6JI5) via occupying the hydrophobic pocket with the dihydroquinoxalinone core, forming hydrogen bonds with TYR97 and ASN140 and water-bridged interactions with PRO86 and GLN85 to enhance binding affinity[1].

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

KWZL-7f15 Related Antibodies

Cell Cycle Analysis[1]

Cell Line: MDA-MB-231
Concentration: 0.25-1 μM
Incubation Time: 48 h
Result: Induced G0/G1 phase arrest in a dose-dependent manner.

Apoptosis Analysis[1]

Cell Line: MDA-MB-231
Concentration: 1 μM
Incubation Time: 48 h
Result: Promoted caspase-dependent apoptosis.
Reversed cytotoxicity when co-treated with pan-caspase inhibitor Z-VAD-FMK.
Parmacokinetics
Species Dose Route Cmax Tmax AUC0-t T1/2 Vd CL MRT0-∞
Rat[1] 5 mg/kg i.p. 160.60 ng/mL 6.00 h 2114.18 13.06 h 420.19 L/kg 22.84 L/h/kg 20.73 h
In Vivo

KWZL-7f15 (compound 7f15) (20-40 mg/kg; i.p.; daily; 14 days) exhibits dose-dependent in vivo antitumor activity in a BALB/c nude mouse MDA-MB-231 xenograft model, achieving a tumor growth inhibition rate of 84.69% at the 40 mg/kg (i.p., daily for 14 days) dose without significant systemic toxicity[1].

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

Animal Model: BALB/c nude (female, 4−5 weeks old, 18−20 g, subcutaneous xenograft model via MDA-MB-231 tumor cell implantation)[1]
Dosage: 20 mg/kg; 40 mg/kg
Administration: i.p.; daily; 14 days
Result: Produced a tumor growth inhibition (TGI) rate of 61.64% at 20 mg/kg.
Produced a TGI rate of 84.69% at 40 mg/kg, which was higher than the TGI rate of the Abemaciclib + BQ0 combination control.
Caused no significant body weight loss.
Showed no treatment-related lesions in heart, liver, spleen, lung, and kidney via histopathological analysis.
Reduced positive expression of c-Myc and p-Rb significantly in tumor tissues compared to the control group via immunohistochemical analysis.
Molecular Weight

490.58

Formula

C26H31FN8O
SMILES

CN(C(C=C1)=C(N(C(C)C)[C@@H]2C)C=C1C3=C(F)C=NC(NC4=CC=C(N5CCNCC5)C=N4)=N3)C2=O
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
References
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KWZL-7f15 Related Classifications

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Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

KWZL-7f15Epigenetic Reader DomainBRD4triple-negative breast cancerRB axisBT-549CDK6Myc axisCDK4MDA-MB-231BETMCF-10AInhibitorinhibitorinhibit

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