Cat. No.: HY-175321

PROTAC c-Met degrader-6

PROTAC c-Met degrader-6 is an orally active c-Met PROTAC degrader with DC₅₀ values of 0.52 nM (EBC-1) and 0.45 nM (Hs746T), respectively. PROTAC c-Met degrader-6 induces potent targeted degradation of c-Met via the ubiquitin-proteasome system by bridging the target protein c-Met and the Cullin-CRBN E3 ubiquitin ligase to form a ternary complex, thereby inducing tumor cell cycle arrest and apoptosis. PROTAC c-Met degrader-6 can be used in the research of various MET-driven cancers (such as gastric cancer, liver cancer, non-small cell lung cancer, etc.).
(Pink: c-Met ligand (HY-W425461); Blue: Cereblon ligand (HY-14658); Black: linker (HY-20797)).

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

Formula: C₄₁H₃₅N₉O₆
Molecular Weight:749.77

Storage:

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

Data Sheet (278 KB)

PROTAC c-Met degrader-6 Chemical Structure

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Use of MCE Products

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 c-Met degrader-6 is an orally active c-Met PROTAC degrader with DC₅₀ values of 0.52 nM (EBC-1) and 0.45 nM (Hs746T), respectively. PROTAC c-Met degrader-6 induces potent targeted degradation of c-Met via the ubiquitin-proteasome system by bridging the target protein c-Met and the Cullin-CRBN E3 ubiquitin ligase to form a ternary complex, thereby inducing tumor cell cycle arrest and apoptosis. PROTAC c-Met degrader-6 can be used in the research of various MET-driven cancers (such as gastric cancer, liver cancer, non-small cell lung cancer, etc.)^[1]. (Pink: c-Met ligand (HY-W425461); Blue: Cereblon ligand (HY-14658); Black: linker (HY-20797)).

IC₅₀ & Target

^[1]

c-Met

0.52 nM (DC₅₀, EBC-1)

c-Met

0.45 nM (DC₅₀, Hs746T)

p-STAT3

All PROTACs Isoforms :

All STAT Isoforms :

Cellular Effect

Cell Line	Type	Value	Description	References
EBC-1	IC50	3.55 nM	Antiproliferative activity against human EBC-1 cancer cells assessed as reduction in cell viability incubated for 96 hrs by CCK-8 assay. Antiproliferative activity against human EBC-1 cancer cells assessed as reduction in cell viability incubated for 96 hrs by CCK-8 assay.	40665847
Hs746T	IC50	3.01 nM	Antiproliferative activity against human Hs746T cancer cells assessed as reduction in cell viability incubated for 96 hrs by CCK-8 assay. Antiproliferative activity against human Hs746T cancer cells assessed as reduction in cell viability incubated for 96 hrs by CCK-8 assay.	40665847
MHCC97H	IC50	7.48 nM	Antiproliferative activity against human MHCC97H cancer cells assessed as reduction in cell viability incubated for 96 hrs by CCK-8 assay. Antiproliferative activity against human MHCC97H cancer cells assessed as reduction in cell viability incubated for 96 hrs by CCK-8 assay.	40665847
NCI-N87	IC50	11.4 nM	Antiproliferative activity against human NCI-N87 cancer cells assessed as reduction in cell viability incubated for 96 hrs by CCK-8 assay. Antiproliferative activity against human NCI-N87 cancer cells assessed as reduction in cell viability incubated for 96 hrs by CCK-8 assay.	40665847
L02	IC50	>100 μM	Antiproliferative activity against human L02 normal cells assessed as reduction in cell viability incubated for 96 hrs by CCK-8 assay. Antiproliferative activity against human L02 normal cells assessed as reduction in cell viability incubated for 96 hrs by CCK-8 assay.	40665847
HEK-293T	IC50	>100 μM	Antiproliferative activity against human HEK293T normal cells assessed as reduction in cell viability incubated for 96 hrs by CCK-8 assay. Antiproliferative activity against human HEK293T normal cells assessed as reduction in cell viability incubated for 96 hrs by CCK-8 assay.	40665847
HMEC	IC50	>100 μM	Antiproliferative activity against human HMEC normal cells assessed as reduction in cell viability incubated for 96 hrs by CCK-8 assay. Antiproliferative activity against human HMEC normal cells assessed as reduction in cell viability incubated for 96 hrs by CCK-8 assay.	40665847
BEAS-2B	IC50	>100 μM	Antiproliferative activity against human BEAS-2B normal cells assessed as reduction in cell viability incubated for 96 hrs by CCK-8 assay. Antiproliferative activity against human BEAS-2B normal cells assessed as reduction in cell viability incubated for 96 hrs by CCK-8 assay.	40665847
EBC-1	DC₅₀	0.52 nM	c-Met protein degradation activity in human EBC-1 cancer cells after 48 h of incubation. c-Met protein degradation activity in human EBC-1 cancer cells after 48 h of incubation.	40665847
Hs746T	DC₅₀	0.45 nM	c-Met protein degradation activity in human Hs746T cancer cells after 48 h of incubation. c-Met protein degradation activity in human Hs746T cancer cells after 48 h of incubation.	40665847

In Vitro

PROTAC c-Met degrader-6 (Compound G4) (1-10 nM; 48 h) significantly and dose-dependently degrades c-Met protein in EBC-1 and Hs746T cells, with DC₅₀ values of 0.52 nM and 0.45 nM, respectively, and reduces the phosphorylation levels of c-Met and STAT3. It potently induces apoptosis and G0/G phase cell cycle arrest, and significantly inhibits cell migration and invasion when combined with Mitomycin C (HY-13316) treatment^[1].

PROTAC c-Met degrader-6 (100-1000 nM; 48 h-12 days) potently inhibits cell proliferation, significantly reduces colony formation, partially to completely degrades c-Met protein, and suppresses its phosphorylation in c-Met D1228N and Y1230H mutant drug-resistant EBC-1 and Hs746T cells^[1].

PROTAC c-Met degrader-6 (up to 100 μM; 72 h) exhibits no obvious cytotoxicity in normal cell lines (LO2, HEK293T, HMEC, BEAS-2B), with an IC₅₀ value >100 μM.

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

Western Blot Analysis^[1]

Cell Line:

EBC-1 and Hs746T cells
Concentration:

1 nM, 10 nM
Incubation Time:

48 h
Result:

Potently and dose-dependently degraded c-Met protein (maximum degradation rate >96%) and almost completely abrogated the phosphorylation levels of c-Met and STAT3.

Apoptosis Analysis^[1]

Cell Line:

EBC-1 and Hs746T cells
Concentration:

10 nM
Incubation Time:

48 h
Result:

Significantly induced cancer cell apoptosis (apoptosis rate of 21.8% in EBC-1 cells), outperforming the control inhibitor tepotinib.

Cell Cycle Analysis^[1]

Cell Line:

EBC-1 and Hs746T cells
Concentration:

10 nM
Incubation Time:

48 h
Result:

Significantly arrested the cell cycle at the G0/G1 phase, with stronger arrest activity than tepotinib.

Cell Migration Assay ^[1]

Cell Line:

EBC-1 and Hs746T cells
Concentration:

5 nM (combined with 1 μM Mitomycin C)
Incubation Time:

12 h, 24 h
Result:

Inhibited the migration capacity of cancer cells.

Cell Invasion Assay^[1]

Cell Line:

EBC-1 and Hs746T cells
Concentration:

5 nM (combined with 1 μM Mitomycin C)
Incubation Time:

24 h
Result:

Significantly reduced the number of invasive cells crossing the Matrigel, inhibiting the invasion capacity of the cells.

Cell Proliferation Assay^[1]

Cell Line:

EBC-1 and Hs746T cells expressing c-Met D1228N and Y1230H mutations
Concentration:

100 nM
Incubation Time:

12 days
Result:

Inhibited the colony formation ability of the resistant cells, far superior to crizotinib and tepotinib.

Western Blot Analysis^[1]

Cell Line:

EBC-1 and Hs746T cells expressing c-Met D1228N and Y1230H mutations
Concentration:

100 nM, 1000 nM
Incubation Time:

48 h
Result:

Partially inhibited at 100 nM and completely degraded the mutant c-Met protein and blocked its phosphorylation at 1000 nM, demonstrating its potential to overcome clinical resistance mutations.

Parmacokinetics

Species	Dose	Route	T_1/2	AUC_0-t	AUC_0-∞	V_ss	CL	T_max	C_max	F
Mice^[1]	1 mg/kg	i.v.	4.94 h	1262.8 ng·h/mL	1298.9 ng·h/mL	3.90 L/kg	0.79 L/h/kg	/	/	/
Mice^[1]	20 mg/kg	p.o.	11.42 h	1848.0 ng·h/mL	1929.9 ng·h/mL	/	/	1.80 h	156.0 ng/mL	7.43 %

In Vivo

PROTAC c-Met degrader-6 (Compound G4) (5-10 mg/kg; p.o.; once daily; for 18 consecutive days) potently and dose-dependently inhibits tumor growth without causing significant body weight loss or toxicity in a subcutaneous EBC-1 cell xenograft model using NOD/SCID immunodeficient mice^[1].

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

Animal Model:

NOD/SCID (6-week-old; subcutaneous EBC-1 cell xenograft model)^[1]
Dosage:

5 mg/kg; 10 mg/kg
Administration:

p.o.; once daily; 18 days
Result:

Achieved a tumor growth inhibition (TGI) of 84.12% with a mean tumor volume of 514.4 mm³ after 10 days at 5 mg/kg.
Achieved a tumor growth inhibition (TGI) of 99.28% with a mean tumor volume of 143.4 mm³ after 10 days at 10 mg/kg.
Induced complete tumor inhibition by day 18 at 10 mg/kg.
Resulted in tumor volumes approximately one-third that of the 2.5 mg/kg tepotinib group by day 18 at 5 mg/kg.
Reduced Ki67 and CD31-positive cells, increased cleaved caspase 3-positive cells, and significantly reduced c-Met, phosphorylated c-Met, and phosphorylated STAT3 protein levels compared to vehicle control at both doses.
Showed no obvious body weight loss or toxic signs at both doses.

Chemical Information

Molecular Weight 749.77
Formula C₄₁H₃₅N₉O₆
SMILES

O=C1NC(CCC1N(C(C2=CC(N3CCN(CC3)CCOC4=CN=C(N=C4)C5=CC=CC(CN6C(C=CC(C7=CC(C#N)=CC=C7)=N6)=O)=C5)=CC=C82)=O)C8=O)=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

Select Batch:

Purity: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (278 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]. Jia C, et al. Novel Highly Potent c-Met Degraders against a Broad Range of Cancers. Journal of medicinal chemistry. 2025 Jul 24;68(14):15176-15197. [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.

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PROTAC c-Met degrader-6

All PROTACs Isoforms

All STAT Isoforms