Cat. No.: HY-175320

PROTAC c-Met degrader-5

PROTAC c-Met degrader-5 is an orally active c-Met PROTAC degrader. PROTAC c-Met degrader-5 induces c-Met degradation via Cullin-CRBN, with a DC₅₀ value of 0.32 nM, and inhibits the phosphorylation of c-Met and its downstream signaling molecule STAT3. PROTAC c-Met degrader-5 inhibits cancer cell proliferation, migration and invasion, induces apoptosis, alters cell cycle distribution, and suppresses the growth of EBC-1 xenograft tumors. PROTAC c-Met degrader-5 can be used to study MET-driven cancers as well as Tepotinib (HY-14721)-resistant cancers harboring c-Met^D1228N and c-Met^Y1230H mutations.
(Pink: c-Met/HGFR ligand (HY-W425461); Blue: Cereblon ligand (HY-14658); Black: linker).

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

Formula: C₄₇H₄₆N₁₀O₆
Molecular Weight:846.93

Storage:

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

Data Sheet (286 KB)

PROTAC c-Met degrader-5 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-5 is an orally active c-Met PROTAC degrader. PROTAC c-Met degrader-5 induces c-Met degradation via Cullin-CRBN, with a DC₅₀ value of 0.32 nM, and inhibits the phosphorylation of c-Met and its downstream signaling molecule STAT3. PROTAC c-Met degrader-5 inhibits cancer cell proliferation, migration and invasion, induces apoptosis, alters cell cycle distribution, and suppresses the growth of EBC-1 xenograft tumors. PROTAC c-Met degrader-5 can be used to study MET-driven cancers as well as Tepotinib (HY-14721)-resistant cancers harboring c-Met^D1228N and c-Met^Y1230H mutations^[1]. (Pink: c-Met/HGFR ligand (HY-W425461); Blue: Cereblon ligand (HY-14658); Black: linker).

IC₅₀ & Target

^[1]

c-Met

0.32 nM (DC₅₀, Hs746T)

c-Met

0.42 nM (DC₅₀, EBC-1)

p-STAT3

All PROTACs Isoforms :

All STAT Isoforms :

Cellular Effect

Cell Line	Type	Value	Description	References
EBC-1	IC₅₀	1.11 nM	Antiproliferative activity against human EBC-1 cells assessed as reduction in cell viability incubated for 96 hrs by CCK-8 assay. Antiproliferative activity against human EBC-1 cells assessed as reduction in cell viability incubated for 96 hrs by CCK-8 assay.	40665847
Hs746T	IC₅₀	1.82 nM	Antiproliferative activity against human Hs746T cells assessed as reduction in cell viability incubated for 96 hrs by CCK-8 assay. Antiproliferative activity against human Hs746T cells assessed as reduction in cell viability incubated for 96 hrs by CCK-8 assay.	40665847
EBC-1	IC₅₀	0.97 nM	Antiproliferative activity against human EBC-1 cancer cells assessed as inhibition of cell proliferation. Antiproliferative activity against human EBC-1 cancer cells assessed as inhibition of cell proliferation.	40665847
Hs746T	IC₅₀	1.60 nM	Antiproliferative activity against human Hs746T cancer cells assessed as inhibition of cell proliferation. Antiproliferative activity against human Hs746T cancer cells assessed as inhibition of cell proliferation.	40665847
MHCC97H	IC₅₀	5.25 nM	Antiproliferative activity against human MHCC97H cancer cells assessed as inhibition of cell proliferation. Antiproliferative activity against human MHCC97H cancer cells assessed as inhibition of cell proliferation.	40665847
EBC-1	DC₅₀	0.42 nM	c-Met protein degradation potency in human EBC-1 cancer cells measured via assessment of c-Met protein levels. c-Met protein degradation potency in human EBC-1 cancer cells measured via assessment of c-Met protein levels.	40665847
Hs746T	DC₅₀	0.32 nM	c-Met protein degradation potency in human Hs746T cancer cells measured via assessment of c-Met protein levels. c-Met protein degradation potency in human Hs746T cancer cells measured via assessment of c-Met protein levels.	40665847
EBC-1	IC₅₀	0.95 nM	Antiproliferative activity against human tepotinib-sensitive EBC-1 Vector cancer cells assessed as inhibition of cell proliferation. Antiproliferative activity against human tepotinib-sensitive EBC-1 Vector cancer cells assessed as inhibition of cell proliferation.	40665847
EBC-1	IC₅₀	31.07 nM	Antiproliferative activity against human tepotinib-resistant EBC-1D1228N cancer cells (harboring c-MetD1228N mutation) assessed as inhibition of cell proliferation. Antiproliferative activity against human tepotinib-resistant EBC-1D1228N cancer cells (harboring c-MetD1228N mutation) assessed as inhibition of cell proliferation.	40665847
EBC-1	IC₅₀	50.30 nM	Antiproliferative activity against human tepotinib-resistant EBC-1Y1230H cancer cells (harboring c-MetY1230H mutation) assessed as inhibition of cell proliferation. Antiproliferative activity against human tepotinib-resistant EBC-1Y1230H cancer cells (harboring c-MetY1230H mutation) assessed as inhibition of cell proliferation.	40665847
Hs746T	IC₅₀	1.17 nM	Antiproliferative activity against human tepotinib-sensitive Hs746TVector cancer cells assessed as inhibition of cell proliferation. Antiproliferative activity against human tepotinib-sensitive Hs746TVector cancer cells assessed as inhibition of cell proliferation.	40665847
Hs746T	IC₅₀	62.37 nM	Antiproliferative activity against human tepotinib-resistant Hs746TD1228N cancer cells (harboring c-MetD1228N mutation) assessed as inhibition of cell proliferation. Antiproliferative activity against human tepotinib-resistant Hs746TD1228N cancer cells (harboring c-MetD1228N mutation) assessed as inhibition of cell proliferation.	40665847
Hs746T	IC₅₀	40.80 nM	Antiproliferative activity against human tepotinib-resistant Hs746TY1230H cancer cells (harboring c-MetY1230H mutation) assessed as inhibition of cell proliferation. Antiproliferative activity against human tepotinib-resistant Hs746TY1230H cancer cells (harboring c-MetY1230H mutation) assessed as inhibition of cell proliferation.	40665847

In Vitro

PROTAC c-Met degrader-5 (10 nM; 48 h) significantly induces apoptosis in Hs746T cells^[1].
PROTAC c-Met degrader-5 (compound D19) (0.01-100 nM; 72 h) dose-dependently degrades c-Met protein in EBC-1 cells over 72 h, with significant degradation starting at 0.1 nM and near-complete degradation at 100 nM^[1].
PROTAC c-Met degrader-5 (0.1-1000 nM; 72 h) dose-dependently degrades c-Met protein in Hs746T cells over 72 h, with significant degradation starting at 0.33 nM and near-complete degradation at 100 nM and higher concentrations^[1].
PROTAC c-Met degrader-5 (10 nM; 3-72 h) time-dependently degrades c-Met protein in EBC-1 cells, with progressive reduction starting at 6 h and near-complete degradation by 72 h^[1].
PROTAC c-Met degrader-5 (10 nM; 3-72 h) time-dependently degrades c-Met protein in Hs746T cells, with progressive reduction starting at 6 h and near-complete degradation by 72 h^[1].
PROTAC c-Met degrader-5 (10 nM; 36 h) significantly downregulates multiple proteins including c-Met, IKZF1, and CD22 in EBC-1 cells, with c-Met showing the largest log₂ fold change of -2.47^[1].
PROTAC c-Met degrader-5 (10 nM; 36 h) alters the expression of proteins in EBC-1 cells that are most significantly enriched in cell adhesion molecules and ECM-receptor interaction pathways^[1].
PROTAC c-Met degrader-5 (1 μM; 48 h) degrades c-Met but does not affect CRBN substrate proteins in EBC-1 cells^[1].
PROTAC c-Met degrader-5 (100-1000 nM; 48 h) degrades c-Met and reduces p-c-Met levels in c-Met^Y1230H mutant EBC-1 cells^[1].
PROTAC c-Met degrader-5 (1 μM; 0-60 min) exhibits improved metabolic stability in mouse and human liver microsomes relative to comparator compound D15^[1].
PROTAC c-Met degrader-5 (10 nM; 48 h) arrests Hs746T cells in the G0/G1 phase, reducing the proportion of cells in the S and G2/M phases^[1].
PROTAC c-Met degrader-5 (5 nM; 12 h) significantly inhibits Hs746T cell migration^[1].
PROTAC c-Met degrader-5 (100 nM; 12 days) significantly inhibits colony formation in c-Met^Y1230H mutant EBC-1 cells^[1].
PROTAC c-Met degrader-5 (10 nM; 36 h) reduces c-Met protein abundance by over 90% in EBC-1 cells, alongside decreases in CRBN substrate IKZF1 and CD22, while other affected proteins align with c-Met signaling inhibition^[1].
PROTAC c-Met degrader-5 (10 nM; 48 h) induces apoptosis in EBC-1 cells at a rate of 31.3%, which is higher than the rates induced by comparator compounds D15 and tepotinib^[1].
PROTAC c-Met degrader-5 (100 nM; 96 h) exhibits synergistic antiproliferative and pro-apoptotic effects when combined with lapatinib, lenvatinib, or vemurafenib in NCI-N87, HepG2, and A375 cells^[1].
PROTAC c-Met degrader-5 (10 nM; 48 h) induces G0/G1 phase cell cycle arrest in EBC-1 cells, with 74.04% of cells in the G0/G1 phase, which is more potent than the arrest induced by D15 and tepotinib^[1].
PROTAC c-Met degrader-5 (5 nM; 24 h) potently inhibits the migration and invasion of EBC-1 cells, with stronger activity than comparator compounds D15 and tepotinib^[1].

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

Western Blot Analysis^[1]

Cell Line:

EBC-1
Concentration:

0.01, 0.033, 0.1, 0.33, 1, 3.3, 10, 33, 100 nM
Incubation Time:

72 h
Result:

Caused a significant reduction in c-Met levels at 0.1 nM.
Induced increasingly potent c-Met degradation at 0.33 nM, 1 nM, 3.3 nM, 10 nM, 33 nM.
Achieved near-complete c-Met degradation at 100 nM.

Western Blot Analysis^[1]

Cell Line:

Hs746T
Concentration:

0.01, 0.033, 0.1, 0.33, 1, 3.3, 10, 33, 100 nM
Incubation Time:

72 h
Result:

Caused a significant reduction in c-Met levels at 0.33 nM.
Induced increasingly potent c-Met degradation at 1 nM, 3.3 nM, 10 nM, 33 nM.
Achieved near-complete c-Met degradation at 100 nM, 330 nM, and 1000 nM.

Western Blot Analysis^[1]

Cell Line:

EBC-1
Concentration:

10 nM
Incubation Time:

3, 6, 12, 24, 36, 48, 60, 72 h
Result:

Gradually reduced c-Met protein levels over time.
Caused visible c-Met reduction starting at 6 h.
Achieved near-complete c-Met degradation by 72 h.

Western Blot Analysis^[1]

Cell Line:

Hs746T
Concentration:

10 nM
Incubation Time:

3, 6, 12, 24, 36, 48, 60, 72 h
Result:

Gradually reduced c-Met protein levels over time.
Caused visible c-Met reduction starting at 6 h.
Achieved near-complete c-Met degradation by 72 h.

Western Blot Analysis^[1]

Cell Line:

EBC-1
Concentration:

1 μM
Incubation Time:

48 h
Result:

Reduced c-Met protein levels relative to vehicle.
Did not alter levels of CRBN substrates IKZF1, IKZF2, IKZF3, SALL4, GSPT1, or CK1α relative to vehicle.

Apoptosis Analysis^[1]

Cell Line:

Hs746T
Concentration:

10 nM
Incubation Time:

48 h
Result:

Significantly increased the percentage of Annexin V-positive apoptotic cells relative to vehicle.

Cell Cycle Analysis^[1]

Cell Line:

Hs746T
Concentration:

10 nM
Incubation Time:

48 h
Result:

Increased the percentage of cells in the G0/G1 phase to 81.00% relative to vehicle's 54.61%.
Decreased the percentage of cells in the S phase to 11.38% relative to vehicle's 32.74%.
Decreased the percentage of cells in the G2/M phase to 7.62% relative to vehicle's 12.66%.
Caused significant differences in cell cycle phase distribution.

Cell Migration Assay^[1]

Cell Line:

Hs746T
Concentration:

5 nM
Incubation Time:

12 h
Result:

Significantly reduced relative cell migration and invasion compared to vehicle.

Western Blot Analysis^[1]

Cell Line:

EBC-1^Y1230H (c-Met Y1230H mutant)
Concentration:

100, 1000 nM
Incubation Time:

48 h
Result:

Reduced c-Met and p-c-Metprotein levels at both 100 nM and 1000 nM doses relative to vehicle.

Western Blot Analysis^[1]

Cell Line:

Hs746T^Y1230H(c-Met Y1230H mutant)
Concentration:

100, 1000 nM
Incubation Time:

48 h
Result:

Reduced c-Met and p-c-Metprotein levels at both 100 nM and 1000 nM doses relative to vehicle.

Apoptosis Analysis^[1]

Cell Line:

EBC-1 cancer cells
Concentration:

10 nM
Incubation Time:

48 h
Result:

Induced an apoptosis rate of 31.3% in EBC-1 cells.

Cell Cycle Analysis^[1]

Cell Line:

EBC-1 cancer cells
Concentration:

10 nM
Incubation Time:

48 h
Result:

Induced G0/G1 phase cell cycle arrest, with 74.04% of cells in the G0/G1 phase.

Cell Proliferation Assay^[1]

Cell Line:

NCI-N87, HepG2, A375 cancer cells
Concentration:

100 nM
Incubation Time:

96 h
Result:

Exerted synergistic antiproliferative activity when combined with Lapatinib, Lenvatinibin or Vemurafenib NCI-N87, HepG2, and A375 cells.
Increased cleaved-PARP levels when combined with Lapatinib, Lenvatinibin or Vemurafenib, indicating enhanced apoptosis induction.

Parmacokinetics

Species	Dose	Route	T_1/2	AUC_0-t	AUC_0-∞	V_ss	CL	T_max	C_max	Bioavailability
Mice^[1]	1 mg/kg	i.v.	9.93 h	1163.2 ng/mL·h	1201.7 ng/mL·h	9.95 L/kg	0.85 L/h/kg	/	/	/
Mice^[1]	20 mg/kg	p.o.	12.47 h	1759.7 ng/mL·h	1812.7 ng/mL·h	/	/	5.20 h	81.27 ng/mL	7.54 %

In Vivo

PROTAC c-Met degrader-5 (compound D19) (5-10 mg/kg; p.o.; once daily for 18 consecutive days) achieves 91.92% tumor growth inhibition at a daily dose of 5 mg/kg, while at a daily dose of 10 mg/kg, it achieves 98.44% tumor growth inhibition and complete tumor regression in NOD/SCID mice bearing EBC-1 xenografts, with no toxicity observed^[1].

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

Animal Model:

NOD/SCID (6-week-old, unspecified gender, subcutaneously injected with 5×10⁶ EBC-1 cells into dorsal flank)^[1]
Dosage:

5, 10 mg/kg
Administration:

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

Achieved a tumor growth inhibition (TGI) of 91.92% with a mean tumor volume of 325.4 mm³ after 10 days of 5 mg/kg dose treatment.
Achieved a TGI of 98.44% with a mean tumor volume of 156.6 mm³ after 10 days of 10 mg/kg dose treatment.
Maintained complete tumor inhibition by day 18 with 10 mg/kg dose treatment.
Resulted in a tumor volume approximately one-third that of the 2.5 mg/kg tepotinib group by day 18 with 5 mg/kg dose treatment.
Showed no obvious body weight loss or toxic signs during treatment.
Reduced Ki67 and CD31-positive cells in harvested tumors.
Increased cleaved caspase 3-positive cells in harvested tumors.
Demonstrated significant reduction of c-Met, p-c-Met, and p-STAT3 levels compared to vehicle contro.

Chemical Information

Molecular Weight 846.93
Formula C₄₇H₄₆N₁₀O₆
SMILES

O=C1C=CC(C2=CC(C#N)=CC=C2)=NN1CC3=CC(C4=NC=C(C=N4)OCC5CCN(CC5)CCN6CCN(CC6)C7=CC=C(C8=C7)C(N(C8=O)C9C(NC(CC9)=O)=O)=O)=CC=C3
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 (286 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]

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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-5

All PROTACs Isoforms

All STAT Isoforms