Cat. No.: HY-170852

QZ2135

QZ2135 is a CRBN-recruiting PROTAC degrader targeting RET kinase, with a DC₅₀ of 4.7 nM. QZ2135 induces RET degradation via the ubiquitin-proteasome system, while blocking RET phosphorylation and downstream signaling pathways, thereby inhibiting the proliferation and inducing apoptosis of cancer cells expressing wild-type or mutant RET. QZ2135 is applicable for cancer research.
(Pink: RET ligand (HY-170853); Blue: Cereblon ligand (HY-W039233); Black: linker (HY-W587352)).

Nos produits utilisent uniquement pour la recherche. Nous ne vendons pas aux patients.

Formule: C₅₃H₅₄N₁₂O₄
Masse moléculaire:923.07

Stockage:

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

Data Sheet (290 KB)

QZ2135 Chemical Structure

Stock

Quantité

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Use of MCE Products

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

Activité biologique
- Description
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- Parmacokinetics
- In Vivo
Chemical Information
Pureté et documentation
Références
Calculators
Help & FAQs
Classifications
Bioz

Activité biologique

Description

QZ2135 is a CRBN-recruiting PROTAC degrader targeting RET kinase, with a DC₅₀ of 4.7 nM. QZ2135 induces RET degradation via the ubiquitin-proteasome system, while blocking RET phosphorylation and downstream signaling pathways, thereby inhibiting the proliferation and inducing apoptosis of cancer cells expressing wild-type or mutant RET. QZ2135 is applicable for cancer research^[1]. (Pink: RET ligand (HY-170853); Blue: Cereblon ligand (HY-W039233); Black: linker (HY-W587352)).

IC₅₀ & Target

^[1]

RET

4.7 nM (DC₅₀)

Voir tous les produits spécifiques à Isoform PROTACs :

Cellular Effect

Cell Line	Type	Value	Description	References
BaF3	IC₅₀	0.01 μM	Antiproliferative activity against Ba/F3-KIF5B-RET (WT) cells assessed as reduction in cell viability incubated for 72 hrs by CCK8 assay. Antiproliferative activity against Ba/F3-KIF5B-RET (WT) cells assessed as reduction in cell viability incubated for 72 hrs by CCK8 assay.	39731581
KBALB-STK	IC₅₀	0.05 μM	Antiproliferative activity against Ba/F3-KIF5B-RET-G810C cells assessed as reduction in cell viability incubated for 72 hrs by CCK8 assay. Antiproliferative activity against Ba/F3-KIF5B-RET-G810C cells assessed as reduction in cell viability incubated for 72 hrs by CCK8 assay.	39731581
BaF3	IC₅₀	0.15 μM	Antiproliferative activity against Ba/F3-KIF5B-RET-G810R cells assessed as reduction in cell viability incubated for 72 hrs by CCK8 assay. Antiproliferative activity against Ba/F3-KIF5B-RET-G810R cells assessed as reduction in cell viability incubated for 72 hrs by CCK8 assay.	39731581
BaF3	DC₅₀	4.7 nM	Induction of dose-dependent RET degradation in Ba/F3-KIF5B-RET cells measured via Western blotting normalized to actin after 6 h treatment. Induction of dose-dependent RET degradation in Ba/F3-KIF5B-RET cells measured via Western blotting normalized to actin after 6 h treatment.	39731581
BaF3	DC₅₀	17.2 nM	Induction of dose-dependent RET V804M mutant degradation in Ba/F3-KIF5B-RET-V804M cells measured via Western blotting normalized to actin after 6 h treatment. Induction of dose-dependent RET V804M mutant degradation in Ba/F3-KIF5B-RET-V804M cells measured via Western blotting normalized to actin after 6 h treatment.	39731581
BaF3	DC₅₀	73.8 nM	Induction of dose-dependent RET G810C mutant degradation in Ba/F3-KIF5B-RET-G810C cells measured via Western blotting normalized to actin after 6 h treatment. Induction of dose-dependent RET G810C mutant degradation in Ba/F3-KIF5B-RET-G810C cells measured via Western blotting normalized to actin after 6 h treatment.	39731581
BaF3	DC₅₀	> 300 nM	Induction of partial RET G810R mutant degradation in Ba/F3-KIF5B-RET-G810R cells measured via Western blotting normalized to actin after 6 h treatment. Induction of partial RET G810R mutant degradation in Ba/F3-KIF5B-RET-G810R cells measured via Western blotting normalized to actin after 6 h treatment.	39731581
BaF3	IC₅₀	0.04 μM	Antiproliferative activity against Ba/F3-KIF5B-RET-V804M cells assessed as reduction in cell viability incubated for 72 hrs by CCK8 assay. Antiproliferative activity against Ba/F3-KIF5B-RET-V804M cells assessed as reduction in cell viability incubated for 72 hrs by CCK8 assay.	39731581
BaF3	IC₅₀	0.05 μM	Antiproliferative activity against Ba/F3-KIF5B-RET-V804L cells assessed as reduction in cell viability incubated for 72 hrs by CCK8 assay. Antiproliferative activity against Ba/F3-KIF5B-RET-V804L cells assessed as reduction in cell viability incubated for 72 hrs by CCK8 assay.	39731581
BaF3	IC₅₀	0.09 μM	Antiproliferative activity against Ba/F3-KIF5B-RET-G810S cells assessed as reduction in cell viability incubated for 72 hrs by CCK8 assay. Antiproliferative activity against Ba/F3-KIF5B-RET-G810S cells assessed as reduction in cell viability incubated for 72 hrs by CCK8 assay.	39731581

In Vitro

QZ2135 (compound 20) inhibits the kinase activities of wild-type and purified RET, with IC₅₀ values of 5.705 nM and 5.7 nM^[1].
QZ2135 (10-1000 nM; 6 h) reduces RET protein levels in Ba/F3-KIF5B-RET cells and human lung adenocarcinoma LC-2/ad cells in a dose-dependent manner^[1].
QZ2135 (333.3-3000 nM; 6 h) dose-dependently reduces the RET protein level in Ba/F3-KIF5B-RET^G810R cells and inhibits the level of downstream phosphorylated Shc^[1].
QZ2135 (0.4-1000 nM; 0.5-24 h) induces time- and dose-dependent RET degradation in Ba/F3-KIF5B-RET cells via the ubiquitin-proteasome system, with a DC₅₀ of 4.7 nM and a D_max of 83%, and exerts a sustained effect even after washout^[1].
QZ2135 (3.7-300 nM; 6 h) induces dose-dependent degradation of the RET^V804M mutant in Ba/F3-KIF5B-RET^V804M cells, with a DC₅₀ of 17.2 nM^[1].
QZ2135 (3.7-300 nM; 6 h) induces dose-dependent degradation of the RET^G810C mutant in Ba/F3-KIF5B-RET^G810C cells, with a DC₅₀ of 73.8 nM^[1].
QZ2135 (3.7-300 nM; 6 h) induces partial degradation of the RET^G810R mutant in Ba/F3-KIF5B-RET^G810R cells, with a degradation rate of approximately 43% at the concentration of 300 nM and a DC₅₀ > 300 nM^[1].
QZ2135 (11.1 nM; 6 h) induces 61.6% degradation of the RET fusion protein in human lung adenocarcinoma LC-2/ad cells^[1].
QZ2135 (11.1-3000 nM; 6 h) inhibits the RET signaling pathway by suppressing the phosphorylation of RET and its downstream effector Shc in Ba/F3 cells expressing wild-type and mutant RET^G810C/R^[1].
QZ2135 (11.1-900 nM; 48 h) induces apoptosis in Ba/F3-KIF5B-RET cells and Ba/F3-KIF5B-RET^G810C cells in a dose-dependent manner^[1].
QZ2135 (72 h) potently inhibits the proliferation of Ba/F3-KIF5B-RET (WT) cells, Ba/F3-KIF5B-RET-G810C cells and Ba/F3-KIF5B-RET-G810R cells, with corresponding IC₅₀ values of 0.01 μM, 0.05 μM and 0.15 μM^[1].
QZ2135 (0.01-0.15 μM; 72 h) potently inhibits the proliferation of Ba/F3 cells expressing wild-type and mutant RET fusion proteins^[1].
QZ2135 (11.1-900 nM; 48 h) induces apoptosis in Ba/F3-KIF5B-RET cells and Ba/F3-KIF5B-RET^G810C cells in a dose-dependent manner^[1].

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

Western Blot Analysis^[1]

Cell Line:

Ba/F3-KIF5B-RET cells
Concentration:

10, 100, 1000 nM
Incubation Time:

6 h
Result:

Dose-dependently reduced RET protein levels in Ba/F3-KIF5B-RET cells after 6 hours of treatment.\nReduced RET protein levels in a dose-dependent manner after 6 hours of treatment.
Left levels of the CRBN neosubstrates GSPT1, CK1α, and IKZF1 unaffected.

Western Blot Analysis^[1]

Cell Line:

human lung adenocarcinoma LC-2/ad cells
Concentration:

1.2, 3.7, 11.1, 33.3, 100 nM
Incubation Time:

6 h
Result:

Dose-dependently reduced RET protein levels in LC-2/ad cells after 6 hours of treatment, with normalized RET/actin gray intensity decreasing as compound concentration increased.

Western Blot Analysis^[1]

Cell Line:

Ba/F3-KIF5B-RET-G810R cells
Concentration:

333.3, 1000, 3000 nM
Incubation Time:

6 h
Result:

Dose-dependently reduced RET protein levels in Ba/F3-KIF5B-RET-G810R cells after 6 hours of treatment.
Suppressed phosphorylated Shc levels (a downstream signaling marker) in Ba/F3-KIF5B-RET-G810R cells after 6 hours of treatment.

Apoptosis Analysis^[1]

Cell Line:

Ba/F3-KIF5B-RET cells, Ba/F3-KIF5B-RET-G810C cells
Concentration:

11.1, 33.3, 100, 300 nM (Ba/F3-KIF5B-RET cells); 33.3, 100, 300, 900 nM (Ba/F3-KIF5B-RET-G810C cells)
Incubation Time:

48 h
Result:

Dose-dependently increased the percentage of apoptotic cells in Ba/F3-KIF5B-RET cells after 48 hours of treatment.
Dose-dependently increased the percentage of apoptotic cells in Ba/F3-KIF5B-RET-G810C cells after 48 hours of treatment.
Induced the largest proportion of apoptotic cells at the highest tested concentrations in both cell lines.

Western Blot Analysis^[1]

Cell Line:

Ba/F3-KIF5B-RET cells
Concentration:

10, 100, 1000 nM (6 h dose-response); 0.4, 1.2, 3.7, 11.1, 33.3, 100, 300, 900 nM (6 h dose-response); 30 nM (time-course); 30 nM (pretreatment + washout); 30 nM (after pretreatment with 500 nM selpercatinib, 1 μM MLN4924, 1 μM MG132, or 10 μM lenalidomide)
Incubation Time:

6 h (dose-dependent); 0.5-12 h (30 nM time-course); 0-24 h (30 nM washout); 6 h (after 2 h pretreatment)
Result:

Induced dose-dependent RET degradation with a DC₅₀ of 4.7 nM and a maximal degradation of 83% after 6 h treatment.
Achieved rapid RET degradation as early as 0.5 h post-treatment with 30 nM, reaching maximal degradation by 2 h.
RET degradation persisted for 2-4 h after compound washout.
Pretreatment with Selpercatinib, MLN4924, MG132, or lenalidomide significantly attenuated RET degradation.

Western Blot Analysis^[1]

Cell Line:

Ba/F3-KIF5B-RET-V804M cells
Concentration:

3.7, 11.1, 33.3, 100, 300 nM
Incubation Time:

6 h
Result:

Induced dose-dependent RET degradation with a DC₅₀ of 17.2 nM.

Western Blot Analysis^[1]

Cell Line:

Ba/F3-KIF5B-RET-G810C cells
Concentration:

3.7, 11.1, 33.3, 100, 300 nM
Incubation Time:

6 h
Result:

Induced dose-dependent RET degradation with a DC₅₀ of 73.8 nM.

Western Blot Analysis^[1]

Cell Line:

Ba/F3-KIF5B-RET-G810R cells
Concentration:

3.7, 11.1, 33.3, 100, 300 nM
Incubation Time:

6 h
Result:

Achieved approximately 43% RET degradation at 300 nM, with a DC₅₀ > 300 nM.

Western Blot Analysis^[1]

Cell Line:

human lung adenocarcinoma LC-2/ad cells (expressing RET fusion protein)
Concentration:

11.1 nM
Incubation Time:

6 h
Result:

Achieved 61.6% RET degradation.

Western Blot Analysis^[1]

Cell Line:

Ba/F3-KIF5B-RET, Ba/F3-KIF5B-RET-V804M, Ba/F3-KIF5B-RET-G810C, and Ba/F3-KIF5B-RET-G810R cells
Concentration:

11.1, 33.3, 100, 300 nM (Ba/F3-KIF5B-RET, Ba/F3-KIF5B-RET-V804M, Ba/F3-KIF5B-RET-G810C); 333.3, 1000, 3000 nM (Ba/F3-KIF5B-RET-G810R)
Incubation Time:

6 h
Result:

Effectively inhibited phosphorylation of RET and Shc in Ba/F3-KIF5B-RET and Ba/F3-KIF5B-RET-V804M cells.
Nearly abolished phosphorylation of RET-G810C and Shc at 300 nM, while selpercatinib showed no suppression at 100 and 300 nM.
Reduced phosphorylation of RET-G810R and Shc at concentrations from 333.3-3000 nM.

Apoptosis Analysis^[1]

Cell Line:

Ba/F3-KIF5B-RET and Ba/F3-KIF5B-RET-G810C cells
Concentration:

11.1, 33.3, 100, 300 nM (Ba/F3-KIF5B-RET); 33.3, 100, 300, 900 nM (Ba/F3-KIF5B-RET-G810C)
Incubation Time:

48 h
Result:

Induced dose-dependent apoptosis, achieving apoptosis rates of 48.3% at 300 nM in Ba/F3-KIF5B-RET cells and 31.8% at 300 nM in Ba/F3-KIF5B-RET-G810C cells.

Parmacokinetics

Species	Dose	Route	T_1/2	AUC_0-∞	CL_{_obs}	V_{ss_obs}	T_max	C_max	F
Mice^[1]	1 mg/kg	i.v.	11.1 h	437 ng/mL·h	44.4 mL/min/kg	31141 mL/kg	/	/	/
Mice^[1]	10 mg/kg	i.p.	6.17 h	680 ng/mL·h	/	/	0.500 h	68.1 ng/mL	17.3 %

In Vivo

QZ2135 (compound 20) (10-30 mg/kg; i.p.; once daily for 3-14 consecutive days of observation) exhibits dose-dependent in vivo antitumor efficacy in Ba/F3-KIF5B-RET^G810C xenograft mice, achieving a TGI of up to 49.2% and RET protein degradation of 55.3% at the dose of 30 mg/kg without obvious toxicity^[1].

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

Animal Model:

BALB/c nude (male, 6 per group, Ba/F3-KIF5B-RET-G810C cell subcutaneous xenograft, tumors grown to ~150 mm³ before treatment)^[1]
Dosage:

10 mg/kg (14-day TGI, 3-day RET degradation); 30 mg/kg (14-day TGI, 14-day tumor weight reduction, 3-day RET degradation)
Administration:

i.p.; once daily for 14 days; i.p.; once daily for 3 days
Result:

Achieved 31.6% tumor growth inhibition (TGI) at 10 mg/kg.
Degraded RET protein in tumors by 47.0% at 10 mg/kg.
Achieved 49.2% TGI at 30 mg/kg.
Reduced tumor weight by 34.4% at 30 mg/kg.
Degraded RET protein in tumors by 55.3% at 30 mg/kg.
Caused no significant body weight changes compared to vehicle controls.

Chemical Information

Masse moléculaire 923.07
Formule C₅₃H₅₄N₁₂O₄
SMILES

N#CC1=C2C(C3=CC=C(N4CC(C5)N(CC6=CC=C(OC)N=C6)C5C4)N=C3)=CC(C7=CN(C8CCN(CCCCCC#CC9=CC=CC%10=C9CN(C(CC%11)C(NC%11=O)=O)C%10=O)CC8)N=C7)=CN2N=C1
Livraison

Room temperature in continental US; may vary elsewhere.
Stockage

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

Pureté et documentation

Select Batch:

Pureté: 99.98%

Assay: 99.98%

ee.: 99.98%

Fiche technique (290 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)
Instruction de manipulation (2659 KB)

Références

[1]. Zhang Q, et al. Discovery of an Efficacious RET PROTAC Degrader with Enhanced Antiproliferative Activity against Resistant Cancer Cells Harboring RET Solvent-Front Mutations. Journal of medicinal chemistry. 2025 Jan 09;68(1):753-775. [Content Brief]

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Help & FAQs

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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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QZ2135

Voir tous les produits spécifiques à Isoform PROTACs