Cat. No.: HY-174368

PROTAC EML4-ALK Degrader-1

Name: PROTAC EML4-ALK Degrader-1
Brand: MedChemExpress
SKU: HY-174368
Availability: PreOrder

(Synonyms: Pro-BA)

PROTAC EML4-ALK Degrader-1 (Pro-BA) is an orally active EML4-ALK PROTAC degrader that recruits GID4, with a K_d value of 144 nM against human EML4-ALK and a DC₅₀ of 74 nM in H3122 cells. PROTAC EML4-ALK Degrader-1 promotes EML4-ALK ubiquitination and proteasomal degradation, reduces cancer cell viability, inhibits cancer cell and tumor growth, induces apoptosis, and alters cell cycle distribution. PROTAC EML4-ALK Degrader-1 can be used in studies related to EML4-ALK-positive cancers and non-small cell lung cancer.
(Pink: EML4-ALK ligand (HY-150908); Blue: GID4 ligand (HY-40114); Black: linker).

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

Formula: C₂₈H₃₅ClN₇O₃P
Molecular Weight:584.05

Storage:

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

Data Sheet (294 KB)

PROTAC EML4-ALK Degrader-1 Chemical Structure

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Top Publications Citing

Use of MCE Products

Fluorescent Dye

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 EML4-ALK Degrader-1 (Pro-BA) is an orally active EML4-ALK PROTAC degrader that recruits GID4, with a K_d value of 144 nM against human EML4-ALK and a DC₅₀ of 74 nM in H3122 cells. PROTAC EML4-ALK Degrader-1 promotes EML4-ALK ubiquitination and proteasomal degradation, reduces cancer cell viability, inhibits cancer cell and tumor growth, induces apoptosis, and alters cell cycle distribution. PROTAC EML4-ALK Degrader-1 can be used in studies related to EML4-ALK-positive cancers and non-small cell lung cancer^[1]. (Pink: EML4-ALK ligand (HY-150908); Blue: GID4 ligand (HY-40114); Black: linker).

IC₅₀ & Target

^[1]

ALK

74 nM (DC₅₀, H3122 cells)

ALK

144 nM (Kd)

All PROTACs Isoforms :

Cellular Effect

Cell Line	Type	Value	Description	References
BaF3	DC₅₀	125 nM	EML4-ALK protein degradation potency in BaF3-EML4-ALK cells assessed via immunoblot analysis after 24 h incubation. EML4-ALK protein degradation potency in BaF3-EML4-ALK cells assessed via immunoblot analysis after 24 h incubation.	40410168
NCI-H3122	DC₅₀	74 nM	Half-maximal EML4-ALK degradation in human H3122 non-small cell lung cancer cells assessed via immunoblot analysis after 24 h treatment. Half-maximal EML4-ALK degradation in human H3122 non-small cell lung cancer cells assessed via immunoblot analysis after 24 h treatment.	40410168
NCI-H3122	IC₅₀	34 nM	Half-maximal inhibition of cell proliferation in human H3122 non-small cell lung cancer cells measured via CCK-8 assay after 48 h treatment. Half-maximal inhibition of cell proliferation in human H3122 non-small cell lung cancer cells measured via CCK-8 assay after 48 h treatment.	40410168
SK-N-BE(2)	DC₅₀	2.1 μM	Half-maximal wild-type ALK degradation in human SK-N-BE(2) neuroblastoma cells assessed via immunoblot analysis. Half-maximal wild-type ALK degradation in human SK-N-BE(2) neuroblastoma cells assessed via immunoblot analysis.	40410168

In Vitro

PROTAC EML4-ALK Degrader-1 (Pro-BA) (1 μM; 0.5-24 h) reduces cell viability in a time-dependent manner in BaF3-EML4-ALK cells^[1].
PROTAC EML4-ALK Degrader-1 (1-1000 nM; 48 h) potently inhibits the proliferation of H3122 cells, with an IC₅₀ value of 34 nM^[1].
PROTAC EML4-ALK Degrader-1 (1 μM; 0.5-24 h) starts inhibiting the growth of BaF3-EML4-ALK cells at 3 h post-treatment^[1].
PROTAC EML4-ALK Degrader-1 (500 nM; 12 h) selectively downregulates EML4-ALK (by more than 40-fold) and its downstream target RRM2 in H3122 cells^[1].
PROTAC EML4-ALK Degrader-1 (5-500 nM; 0.5-24 h) induces concentration- and time-dependent degradation of EML4-ALK in H3122 cells^[1].
PROTAC EML4-ALK Degrader-1 (10-1000 nM; 0.25-24 h) induces concentration-dependent degradation of EML4-ALK in BaF3-EML4-ALK cells with a DC₅₀ of 125 nM; it also induces time-dependent degradation of EML4-ALK with a T_1/2 of 2 h^[1].
PROTAC EML4-ALK Degrader-1 (100 nM; 6 h) induces the degradation of EML4-ALK in H3122 cells via the proteasome pathway^[1].
Combination treatment with PROTAC EML4-ALK Degrader-1 (100 nM; 2-4 h) and Cycloheximide (HY-12320) accelerates the turnover of EML4-ALK in H3122 cells, and this accelerated turnover process is dependent on the proteasome pathway^[1].
PROTAC EML4-ALK Degrader-1 (0.001-20 μM; 24-48 h) potently induces EML4-ALK degradation in H3122 cells, with a DC₅₀ of 74 nM and a maximum degradation rate of 82% at a concentration of 500 nM^[1].
PROTAC EML4-ALK Degrader-1 (250 nM; 0.5-24 h) initiates the degradation of EML4-ALK in H3122 cells at 3 h, with a degradation half-life (T_1/2) of 8 h^[1].
PROTAC EML4-ALK Degrader-1 (5-500 nM; 0.5-24 h) potently induces EML4-ALK degradation in BaF3-EML4-ALK cells, with a DC₅₀ of 125 nM; at a concentration of 250 nM, its T_1/2 is approximately 2 h^[1].
PROTAC EML4-ALK Degrader-1 (1 μM; 0.5-24 h) induces apoptosis in BaF3-EML4-ALK cells starting at 3 h post-treatment^[1].
PROTAC EML4-ALK Degrader-1 (500 nM; 24 h) induces a stronger G1-phase arrest in H3122 cells than linker-containing analogs^[1].
PROTAC EML4-ALK Degrader-1 (500 nM; 24 h) induces a higher level of apoptosis in H3122 cells than its linker-containing counterpart^[1].
PROTAC EML4-ALK Degrader-1 (1 μM; 0.5-24 h) induces time-dependent increases in early and late apoptosis in BaF3-EML4-ALK cells^[1].
PROTAC EML4-ALK Degrader-1 (100-500 nM; 48 h) exhibits superior EML4-ALK degradation activity in H3122 cells compared to its linker-containing analogs, with a DC₅₀ of 74 nM and a maximum degradation rate of 82% at a concentration of 500 nM^[1].

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

Western Blot Analysis^[1]

Cell Line:

H3122 cells
Concentration:

5, 10, 25, 50, 75, 100, 250, 500 nM
Incubation Time:

0.5, 1, 3, 6, 12, 18, 24 h
Result:

Reduced EML4-ALK protein levels in a concentration-dependent manner at 5-500 nM over 24 h.
Reduced EML4-ALK protein levels in a time-dependent manner at 250 nM over 0.5-24 h.

Western Blot Analysis^[1]

Cell Line:

BaF3-EML4-ALK cells
Concentration:

10, 100, 1000 nM
Incubation Time:

0.25, 0.5, 1, 2, 4, 8, 16, 24 h
Result:

Reduced EML4-ALK protein levels in a concentration-dependent manner at 100-1000 nM over 24 h, with a DC₅₀ value of 125 nM.
Reduced EML4-ALK protein levels in a time-dependent manner at 1 μM over 0.5-24 h, with a degradation half-life (T₁/₂) of 2 h.

Cell Viability Assay^[1]

Cell Line:

BaF3-EML4-ALK cells
Concentration:

1 μM
Incubation Time:

0.5, 1, 3, 6, 24 h
Result:

Reduced cell viability in a time-dependent manner, with viability decreasing notably after 3 h of incubation.

Apoptosis Analysis^[1]

Cell Line:

BaF3-EML4-ALK cells
Concentration:

1 μM
Incubation Time:

0.5, 1, 3, 6, 24 h
Result:

Increased the percentages of both early and late apoptotic cells in a time-dependent manner.
Increased early apoptosis from baseline to 7.8% at 24 h.
Increased late apoptosis from baseline to 17.0% at 24 h.

Western Blot Analysis^[1]

Cell Line:

unspecified cells expressing full-length ALK (FL-ALK)
Concentration:

1, 2.5, 5, 7.5, 10 μM
Incubation Time:

24 h
Result:

Reduced FL-ALK protein levels in a concentration-dependent manner, with a DC₅₀ value of 2.1 μM.
Increased levels of cleaved-ALK.

Western Blot Analysis^[1]

Cell Line:

H3122 non-small cell lung cancer cells
Concentration:

100 nM
Incubation Time:

6 h
Result:

Induced a reduction in EML4-ALK protein levels.
Blocked EML4-ALK degradation when co-treated with MG132, with protein levels remaining near control levels.
Showed no effect on EML4-ALK degradation when co-treated with CQ.

Western Blot Analysis^[1]

Cell Line:

H3122 non-small cell lung cancer cells
Concentration:

100 nM
Incubation Time:

2 h, 4 h
Result:

Diminished EML4-ALK protein levels rapidly when combined with CHX.
Hindered EML4-ALK turnover when co-treated with MG132, with protein levels remaining near control levels after 4 h.

Western Blot Analysis^[1]

Cell Line:

H3122 non-small cell lung cancer cells
Concentration:

0.01, 0.1, 1, 10, 20 μM (48 h); 5, 10, 25, 50, 75, 100, 250, 500 nM (24 h)
Incubation Time:

24 h, 48 h
Result:

Induced a significant reduction in EML4-ALK protein levels starting at 100 nM after 48 h.
Achieved an 82% reduction in EML4-ALK levels at 500 nM.
Exhibited a half-maximal degradation concentration (DC₅₀) of 74 nM.

Cell Viability Assay^[1]

Cell Line:

H3122 non-small cell lung cancer cells
Concentration:

1, 10, 100, 1000 nM
Incubation Time:

48 h
Result:

Inhibited H3122 cell proliferation with a half-maximal inhibitory concentration (IC₅₀) of 34 nM.\nWas more potent in blocking H3122 cell growth than linker-bearing counterparts Pro-PEG1-BA and Pro-PEG3-BA.
Exhibited an IC₅₀ of 34 nM.

Western Blot Analysis^[1]

Cell Line:

H3122 non-small cell lung cancer cells
Concentration:

250 nM
Incubation Time:

0.5, 1, 3, 6, 12, 24 h
Result:

Initiated a decrease in EML4-ALK protein levels at 3 h.
Exhibited a degradation half-life (T₁/₂) of 8 h.

Western Blot Analysis^[1]

Cell Line:

BaF3-EML4-ALK cells
Concentration:

100, 250,500, 750, 1000 nM
Incubation Time:

0.5, 1, 3, 6, 12, 24 h
Result:

Efficiently induced EML4-ALK degradation with a DC₅₀ of 125 nM.
Initiated degradation as early as 0.5 h.
Exhibited a degradation half-life (T₁/₂) of ~2 h.

Cell Viability Assay^[1]

Cell Line:

BaF3-EML4-ALK cells
Concentration:

1 μM
Incubation Time:

0.5, 1, 3, 6, 24 h
Result:

Inhibited BaF3-EML4-ALK cell proliferation starting at 3 h post-treatment.

Apoptosis Analysis^[1]

Cell Line:

BaF3-EML4-ALK cells
Concentration:

1 μM
Incubation Time:

0.5, 1, 3, 6, 24 h
Result:

Increased the fraction of both early and late apoptotic cells after 3 h.
Showed no significant change in apoptotic cell fraction within 1 h.

Western Blot Analysis^[1]

Cell Line:

H3122 non-small cell lung cancer cells
Concentration:

100 nM; 500 nM
Incubation Time:

48 h
Result:

Led to a noticeable reduction in EML4-ALK levels at 100 nM.
Exhibited a lower DC₅₀ (74 nM) and higher maximum degradation (Dmax, 82%) compared to linker-bearing counterparts Pro-PEG1-BA and Pro-PEG3-BA.
Showed no overt effect on EML4-ALK levels by linker-bearing counterparts at 100 nM.

Cell Cycle Analysis^[1]

Cell Line:

H3122 non-small cell lung cancer cells
Concentration:

500 nM
Incubation Time:

24 h
Result:

Induced a higher proportion of cells in the G1 phase (86%) and lower proportions in the S (7.8%) and G2 (5.8%) phases compared to linker-bearing counterparts.
Showed milder effects on cell cycle distribution by linker-bearing counterparts.

Apoptosis Analysis^[1]

Cell Line:

H3122 non-small cell lung cancer cells
Concentration:

500 nM
Incubation Time:

24 h
Result:

Led to a marked elevation in the percentage of early and late apoptotic cells.
Induced a comparatively lower apoptotic response by linker-bearing counterparts under the same conditions.

Parmacokinetics

Species	Dose	Route	T_max	T_1/2	C_max	AUC_0-t	V_d	Cl_{F_obs}	MRT_last	F
Mice^[1]	2 mg/kg	i.v.	0.083 h	3.0 h	2.0 μg/mL	2.8 μg/mL·h	3.0 L/kg	681 mL/h/kg	3.1 h	/
Mice^[1]	10 mg/kg	p.o.	0.25 h	3.4 h	2.7 μg/mL	4.9 μg/mL·h	9.4 L/kg	1892 mL/h/kg	3.2 h	35 %

In Vivo

PROTAC EML4-ALK Degrader-1 (Pro-BA) (10 mg/kg; i.p.; once every two days; 8 doses total) potently inhibits the growth of non-small cell lung cancer xenografts and reduces EML4-ALK protein levels in Mus musculus, with no significant toxicity^[1].
PROTAC EML4-ALK Degrader-1 (10 mg/kg; p.o.; single administration) reduces the protein level of EML4-ALK in non-small cell lung cancer xenografts in mice within 48 h^[1].
PROTAC EML4-ALK Degrader-1 (25 mg/kg; p.o.; once every 2 days; 8 administrations total) potently inhibits the growth of non-small cell lung cancer xenografts, reduces EML4-ALK protein levels, and causes no obvious toxicity in mice^[1].

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

Animal Model:

Nude mice (4-week-old female; subcutaneous xenograft of H3122 cells)^[1]
Dosage:

10 mg/kg
Administration:

i.p.; every other day; 8 doses
Result:

Significantly reduced tumor volume relative to vehicle control.
Inhibited tumor growth relative to vehicle control.
Induced a pronounced, consistent decrease in EML4-ALK protein levels in tumor tissue.
Caused no significant changes in mouse body weight.

Animal Model:

Nude mice (tumor-bearing; subcutaneous xenograft of H3122 cells)^[1]
Dosage:

10 mg/kg
Administration:

p.o.; single dose
Result:

Significantly lowered EML4-ALK protein levels in tumor tissue 48 hours after treatment.

Animal Model:

Nude mice (4-week-old female; subcutaneous xenograft of H3122 cells)^[1]
Dosage:

25 mg/kg
Administration:

p.o.; every 2 days; 8 doses
Result:

Significantly shrank tumor volume relative to vehicle control.
Suppressed tumor growth relative to vehicle control.
Reduced EML4-ALK protein levels in tumors confirmed by immunohistochemistry and immunoblot analysis.
Caused no apparent body weight changes.
Showed intact morphology in heart, liver, spleen, lung, and kidney tissues via H&E staining.

Chemical Information

Molecular Weight 584.05
Formula C₂₈H₃₅ClN₇O₃P
SMILES

COC1=C(C=CC(N2CCN(CC2)C([C@H]3CCCN3)=O)=C1)NC4=NC=C(C(NC5=CC=CC=C5P(C)(C)=O)=N4)Cl
Synonyms

Pro-BA
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 (294 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]. Zhang J, et al. Linker-free PROTACs efficiently induce the degradation of oncoproteins. Nature communications. 2025 May 23;16(1):4794. [Content Brief]

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How should lyophilized recombinant proteins be reconstituted and stored?

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PROTAC EML4-ALK Degrader-1

All PROTACs Isoforms