Cat. No.: HY-174315

WZH-17-002

WZH-17-002 is a CRBN‑recruiting ALK PROTAC degrader. WZH‑17‑002 degrades ALK proteins, including EML4‑ALK and the compound mutants. WZH‑17‑002 inhibits the development of drug resistance in ALK‑fusion non‑small‑cell lung cancer. WZH‑17‑002 can be used for research related to non‑small‑cell lung cancer.
(Pink: Anaplastic lymphoma kinase (ALK) ligand (HY-174314); Blue: Cereblon ligand (HY-14658); Black: linker (HY-174316)).

연구목적의 판매만을 진행합니다. 환자를 대상으로 한 판매는 하지 않습니다.

화학식: C₄₇H₅₄BrN₁₁O₁₀S
분자량:1044.97

보관:

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

Data Sheet (288 KB)

WZH-17-002 Chemical Structure

Amount: USD 0.00

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Use of MCE Products

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

Biological Activity
- 제품 설명
- Cellular Effect
- In Vitro
- Parmacokinetics
- In Vivo
Chemical Information
순도&문서
References
Calculators
Help & FAQs
Classifications
Bioz

Biological Activity

제품 설명

WZH-17-002 is a CRBN‑recruiting ALK PROTAC degrader. WZH‑17‑002 degrades ALK proteins, including EML4‑ALK and the compound mutants. WZH‑17‑002 inhibits the development of drug resistance in ALK‑fusion non‑small‑cell lung cancer. WZH‑17‑002 can be used for research related to non‑small‑cell lung cancer^[1]. (Pink: Anaplastic lymphoma kinase (ALK) ligand (HY-174314); Blue: Cereblon ligand (HY-14658); Black: linker (HY-174316)).

All PROTACs Isoforms :

Cellular Effect

Cell Line	Type	Value	Description	References
BaF3	IC50	< 4.6 nM	Antiproliferative activity against Ba/F3 cells expressing EML4-ALK wild-type assessed as reduction in cell viability incubated for 48 hrs by CellTiter-Glo Luminescent cell viability assay. Antiproliferative activity against Ba/F3 cells expressing EML4-ALK wild-type assessed as reduction in cell viability incubated for 48 hrs by CellTiter-Glo Luminescent cell viability assay.	40479896
BaF3	IC50	6.5 nM	Antiproliferative activity against Ba/F3 cells expressing EML4-ALK C1156Y assessed as reduction in cell viability incubated for 48 hrs by CellTiter-Glo Luminescent cell viability assay. Antiproliferative activity against Ba/F3 cells expressing EML4-ALK C1156Y assessed as reduction in cell viability incubated for 48 hrs by CellTiter-Glo Luminescent cell viability assay.	40479896
BaF3	IC50	8.0 nM	Antiproliferative activity against Ba/F3 cells expressing EML4-ALK I1171T assessed as reduction in cell viability incubated for 48 hrs by CellTiter-Glo Luminescent cell viability assay. Antiproliferative activity against Ba/F3 cells expressing EML4-ALK I1171T assessed as reduction in cell viability incubated for 48 hrs by CellTiter-Glo Luminescent cell viability assay.	40479896
BaF3	IC50	11.3 nM	Antiproliferative activity against Ba/F3 cells expressing EML4-ALK G1269A assessed as reduction in cell viability incubated for 48 hrs by CellTiter-Glo Luminescent cell viability assay. Antiproliferative activity against Ba/F3 cells expressing EML4-ALK G1269A assessed as reduction in cell viability incubated for 48 hrs by CellTiter-Glo Luminescent cell viability assay.	40479896
BaF3	IC50	6.4 nM	Antiproliferative activity against Ba/F3 cells expressing EML4-ALK G1202R assessed as reduction in cell viability incubated for 48 hrs by CellTiter-Glo Luminescent cell viability assay. Antiproliferative activity against Ba/F3 cells expressing EML4-ALK G1202R assessed as reduction in cell viability incubated for 48 hrs by CellTiter-Glo Luminescent cell viability assay.	40479896
BaF3	IC50	13.0 nM	Antiproliferative activity against Ba/F3 cells expressing EML4-ALK C1156Y/L1198F assessed as reduction in cell viability incubated for 48 hrs by CellTiter-Glo Luminescent cell viability assay. Antiproliferative activity against Ba/F3 cells expressing EML4-ALK C1156Y/L1198F assessed as reduction in cell viability incubated for 48 hrs by CellTiter-Glo Luminescent cell viability assay.	40479896
BaF3	IC50	17.2 nM	Antiproliferative activity against Ba/F3 cells expressing EML4-ALK G1202R/L1196M assessed as reduction in cell viability incubated for 48 hrs by CellTiter-Glo Luminescent cell viability assay. Antiproliferative activity against Ba/F3 cells expressing EML4-ALK G1202R/L1196M assessed as reduction in cell viability incubated for 48 hrs by CellTiter-Glo Luminescent cell viability assay.	40479896
BaF3	IC50	147.7 nM	Antiproliferative activity against Ba/F3 cells expressing EML4-ALK I1171N/L1256F assessed as reduction in cell viability incubated for 48 hrs by CellTiter-Glo Luminescent cell viability assay. Antiproliferative activity against Ba/F3 cells expressing EML4-ALK I1171N/L1256F assessed as reduction in cell viability incubated for 48 hrs by CellTiter-Glo Luminescent cell viability assay.	40479896
BaF3	IC50	15.0 nM	Antiproliferative activity against Ba/F3 cells expressing EML4-ALK L1196M/D1203N assessed as reduction in cell viability incubated for 48 hrs by CellTiter-Glo Luminescent cell viability assay. Antiproliferative activity against Ba/F3 cells expressing EML4-ALK L1196M/D1203N assessed as reduction in cell viability incubated for 48 hrs by CellTiter-Glo Luminescent cell viability assay.	40479896
NCI-H3122	IC50	4.5 nM	Antiproliferative activity against human ALK-rearranged NSCLC H3122 cells assessed as reduction in cell viability incubated for 48 hrs by CellTiter-Glo Luminescent cell viability assay. Antiproliferative activity against human ALK-rearranged NSCLC H3122 cells assessed as reduction in cell viability incubated for 48 hrs by CellTiter-Glo Luminescent cell viability assay.	40479896
NCI-H2228	IC50	58.6 nM	Antiproliferative activity against human ALK-rearranged NSCLC H2228 cells assessed as reduction in cell viability incubated for 48 hrs by CellTiter-Glo Luminescent cell viability assay. Antiproliferative activity against human ALK-rearranged NSCLC H2228 cells assessed as reduction in cell viability incubated for 48 hrs by CellTiter-Glo Luminescent cell viability assay.	40479896
PC-9	IC50	179.4 nM	Antiproliferative activity against human EGFR-mutated PC9 cells assessed as reduction in cell viability incubated for 48 hrs by CellTiter-Glo Luminescent cell viability assay. Antiproliferative activity against human EGFR-mutated PC9 cells assessed as reduction in cell viability incubated for 48 hrs by CellTiter-Glo Luminescent cell viability assay.	40479896
A549	IC50	> 10000 nM	Antiproliferative activity against human non-ALK-driven NSCLC A549 cells assessed as reduction in cell viability incubated for 48 hrs by CellTiter-Glo Luminescent cell viability assay. Antiproliferative activity against human non-ALK-driven NSCLC A549 cells assessed as reduction in cell viability incubated for 48 hrs by CellTiter-Glo Luminescent cell viability assay.	40479896
NCI-H460	IC50	> 10000 nM	Antiproliferative activity against human non-ALK-driven NSCLC H460 cells assessed as reduction in cell viability incubated for 48 hrs by CellTiter-Glo Luminescent cell viability assay. Antiproliferative activity against human non-ALK-driven NSCLC H460 cells assessed as reduction in cell viability incubated for 48 hrs by CellTiter-Glo Luminescent cell viability assay.	40479896
NCI-H157	IC50	> 10000 nM	Antiproliferative activity against human non-ALK-driven NSCLC H157 cells assessed as reduction in cell viability incubated for 48 hrs by CellTiter-Glo Luminescent cell viability assay. Antiproliferative activity against human non-ALK-driven NSCLC H157 cells assessed as reduction in cell viability incubated for 48 hrs by CellTiter-Glo Luminescent cell viability assay.	40479896
NCI-H292	IC50	> 10000 nM	Antiproliferative activity against human non-ALK-driven NSCLC H292 cells assessed as reduction in cell viability incubated for 48 hrs by CellTiter-Glo Luminescent cell viability assay. Antiproliferative activity against human non-ALK-driven NSCLC H292 cells assessed as reduction in cell viability incubated for 48 hrs by CellTiter-Glo Luminescent cell viability assay.	40479896
BEAS-2B	IC50	> 10000 nM	Antiproliferative activity against human non-tumorigenic lung BEAS-2B cells assessed as reduction in cell viability incubated for 48 hrs by CellTiter-Glo Luminescent cell viability assay. Antiproliferative activity against human non-tumorigenic lung BEAS-2B cells assessed as reduction in cell viability incubated for 48 hrs by CellTiter-Glo Luminescent cell viability assay.	40479896
MRC5	IC50	> 10000 nM	Antiproliferative activity against human non-tumorigenic lung MRC-5 cells assessed as reduction in cell viability incubated for 48 hrs by CellTiter-Glo Luminescent cell viability assay. Antiproliferative activity against human non-tumorigenic lung MRC-5 cells assessed as reduction in cell viability incubated for 48 hrs by CellTiter-Glo Luminescent cell viability assay.	40479896
NCI-H3122	DC₅₀	25.0 nM	ALK protein degradation activity in human ALK-rearranged NSCLC H3122 cells measured by Western blot after 16 h incubation. ALK protein degradation activity in human ALK-rearranged NSCLC H3122 cells measured by Western blot after 16 h incubation.	40479896

In Vitro

WZH-17-002 (< 4.6 nM-10 μM; 48 h) potently inhibits the proliferation of Ba/F3 cells expressing EML4-ALK (wild-type) or Lorlatinib (HY-12215)-resistant EML4-ALK^{G1202R/L1196M}, with IC₅₀ values ranging from < 4.6 nM to 17.2 nM^[1].
WZH-17-002 (< 4.6 nM-10 μM; 48 h) selectively inhibits the proliferation of ALK-rearranged human non-small cell lung cancer cell lines (DFCI076, H3122, H2228), with IC₅₀ values ranging from 4.5 nM to 58.6 nM; it exhibits moderate activity against EGFR-mutated PC9 cells^[1].
WZH-17-002 (1-500 nM; 16 h) degrades ALK protein in ALK-rearranged human non-small cell lung cancer cells (DFCI076, H3122) with a DC₅₀ value of approximately 25 nM, while inhibiting the ALK signaling pathway, degrading the mutant ALK^G12C in ALK inhibitor-resistant Ba/F3 cells, and mediating degradation via a CRBN- and proteasome-dependent pathway^[1].
WZH-17-002 (5-20 nM; 14 days) inhibits colony formation of ALK-rearranged DFCI076 and H2228 non-small cell lung cancer (NSCLC) cells^[1].
WZH-17-002 (50 nM; 70 days) delays the emergence of drug resistance in ALK-rearranged H3122 non-small cell lung cancer cells^[1].

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

Western Blot Analysis^[1]

Cell Line:

Human NSCLC cell lines (H2228, DFCI076, H3122); engineered Ba/F3 cells (EML4-ALK G1202R/L1196M, I1171S/G1269A)
Concentration:

5, 10, 50, 100 nM (H2228, DFCI076); 10, 50, 100, 250, 500 nM (H3122); 10, 50, 100, 250, 500 nM (engineered Ba/F3 cells); 10 nM (DFCI076 with cereblon modulator/NAE inhibitor pretreatment); 100 nM (H3122 with WZH-15-125 pretreatment); 10 nM (DFCI076 with WZH-15-125 pretreatment)
Incubation Time:

2 h pretreatment + 16 h treatment
Result:

Reduced ALK protein levels and inhibited phosphorylation of ALK (Tyr1604), Akt, and ERK in H2228 cells at 5 nM.
Degraded ALK protein in DFCI076 and H3122 cells with DC₅₀ values of ~24.0 nM and 25.0 nM, respectively.
Reduced total ALK protein and phosphorylation levels in a dose-dependent manner in EML4-ALK G1202R/L1196M and I1171S/G1269A Ba/F3 cells.
Diminished ALK degradation was observed when DFCI076 cells were pretreated with cereblon modulator or NAE inhibitor.
Reduced ALK degradation activity in a dose-dependent manner when H3122 and DFCI076 cells were pretreated with WZH-15-125.

Parmacokinetics

Species	Dose	Route	AUC_last	AUC_inf	Cl_{F_obs}	T_1/2	V_{ss_obs}	C_max	T_max	Bioavailability
Rat^[1]	1 mg/kg	i.v.	4279 ng·h/mL	4317 ng·h/mL	4.19 mL/min/kg	3.48 h	0.99 L/kg	/	/	/
Rat^[1]	10 mg/kg	p.o.	3578 ng·h/mL	3675 ng·h/mL	/	4.07 h	/	269 ng/mL	4.67 h	8.5 %

In Vivo

WZH-17-002 (10-20 mg/kg; i.v.; once daily for 10 days) exhibits dose-dependent in vivo efficacy against ALK tyrosine kinase inhibitor-resistant EML4-ALK^{G1202R/L1196M} xenograft tumors in BALB/c nu/nu mice, achieving a maximum TGI of 49.4% at 20 mg/kg i.v. with a favorable safety profile^[1].

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

Animal Model:

BALB/c nu/nu (female, 6-8 weeks of age)^[1]
Dosage:

10 mg/kg; 20 mg/kg
Administration:

i.v.
Result:

Achieved a tumor growth inhibition (TGI) of approximately 35% based on tumor volume and tumor weight at 10 mg/kg.
Achieved a TGI of 49.4% based on tumor volume at 20 mg/kg.
Significantly reduced tumor weight in both treatment groups compared to the vehicle group.
Markedly lowered ALK protein levels in treated tumors compared to ALK tyrosine kinase inhibitor-treated tumors.
Caused no significant body weight loss or other signs of toxicity in either treatment group.

Chemical Information

분자량 1044.97
화학식 C₄₇H₅₄BrN₁₁O₁₀S
SMILES

O=C(N(CC1)CCN1C(CC2)CCN2C(C(CC)=C3)=CC(OC)=C3NC(N=C4NC5=CC=C6OCCOC6=C5N(S(C)(=O)=O)C)=NC=C4Br)CNC7=C8C(N(C9CCC(NC9=O)=O)C(C8=CC=C7)=O)=O
선적

Room temperature in continental US; may vary elsewhere.
보관

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

순도&문서

Select Batch:

Purity: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (288 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]. Gao F, et al. Discovery of an ALK degrader for lorlatinib-resistant compound mutations. European journal of medicinal chemistry. 2025 Oct 15;296:117835. [Content Brief]

Calculators

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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.

Bioz

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WZH-17-002

All PROTACs Isoforms