2. PROTAC Cell Cycle/DNA Damage
  3. PROTACs SWI/SNF Complex
  4. LJM133

LJM133 is a SMARCA2/PBRM1/SMARCA4 PROTAC degrader with DC50 values of 3.5 nM, 7 nM, and 6.4 nM. LJM133 induces ternary complex formation with VHL E3 ligase to drive proteasome-mediated degradation of target proteins. LJM133 suppresses cell proliferation and exhibits significant antitumor efficacy in a SMARCA4 mutant cancer xenograft model. LJM133 can be used for the research of cancer, such as SMARCA4 mutant non-small cell lung cancer. (Pink: SMARCA2/PBRM1/SMARCA4 ligand (HY-182987); E3 ubiquitin ligase ligand-linker conjugate (HY-183619)).

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LJM133

LJM133 Chemical Structure

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LJM133 Related Antibodies

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von Hippel-Lindau (VHL) Cereblon MDM2 cIAP1

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SMARCA2 SMARCA4 Protein Polybromo-1

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Description

LJM133 is a SMARCA2/PBRM1/SMARCA4 PROTAC degrader with DC50 values of 3.5 nM, 7 nM, and 6.4 nM. LJM133 induces ternary complex formation with VHL E3 ligase to drive proteasome-mediated degradation of target proteins. LJM133 suppresses cell proliferation and exhibits significant antitumor efficacy in a SMARCA4 mutant cancer xenograft model. LJM133 can be used for the research of cancer, such as SMARCA4 mutant non-small cell lung cancer[1]. (Pink: SMARCA2/PBRM1/SMARCA4 ligand (HY-182987); E3 ubiquitin ligase ligand-linker conjugate (HY-183619)).

IC50 & Target[1]

VHL

 

SMARCA2

3.5 nM (IC50)

SMARCA4

6.4 nM (IC50)

PBRM1

7 nM (IC50)

In Vitro

LJM133 (Compound 14) potently binds purified SMARCA2BD (IC50 = 79.7 nM), SMARCA4BD (IC50 = 369.5 nM), and PBRM1BD5 (IC50 = 12.1 nM)[1].
LJM133 (5 days) potently inhibits proliferation of NCI-H1944 cells (IC50 = 18 nM) and NCI-H1568 cells (IC50 = 23 nM)[1].
LJM133 (1-100 nM; 2 h) degrades SMARCA2 in NCI-H1944 cells with a DC50 of 8.6 nM[1].
LJM133 (0.1-300 nM; 2 h) degrades SMARCA2 (DC50 = 3.5 nM), SMARCA4 (DC50 = 7.0 nM), and PBRM1 (DC50 = 6.4 nM) in NCI-H1975 cells[1].
LJM133 (30 nM; 2 h) induces proteasome-dependent degradation of SMARCA2 and PBRM1 in NCI-H1568 cells via a canonical PROTAC mechanism requiring target engagement and functional VHL E3 ligase activity[1].
LJM133 (0-24 h) induces rapid degradation of SMARCA2 and PBRM1 in NCI-H1944 cells, with maximal depletion achieved within 2 h[1].
LJM133 (1-100 nM; 18 h) causes dose-dependent downregulation of KRT80 and PLAU mRNA levels in NCI-H1944 cells[1].

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

LJM133 Related Antibodies

Western Blot Analysis[1]

Cell Line: NCI-H1944 SMARCA4-mutant nonsmall cell lung cancer cells
Concentration: 1, 3, 10, 30, 100 nM
Incubation Time: 2 h
Result: Induced robust degradation of SMARCA2, with a DC50 of 8.6 nM.

Western Blot Analysis[1]

Cell Line: NCI-H1975 SMARCA4 wild-type nonsmall cell lung cancer cells
Concentration: 0.1, 0.3, 1, 3, 10, 30, 300 nM
Incubation Time: 2 h
Result: Induced degradation of SMARCA2 with a DC50 of 3.5 nM.
Induced degradation of SMARCA4 with a DC50 of 7.0 nM.
Induced degradation of PBRM1 with a DC50 of 6.4 nM.

Western Blot Analysis[1]

Cell Line: NCI-H1568 SMARCA4-mutant nonsmall cell lung cancer cells
Concentration: 30 nM
Incubation Time: 2 h
Result: Rescued degradation of SMARCA2 and PBRM1 induced by LJM133 via pretreatment with proteasome inhibitor MG132 (HY-13259), cullin-RING E3 ligase inhibitor MLN4924 (HY-70062), SMARCA2/4/PBRM1 ligand 4p (HY-182987), or VHL-binding competitor ARV-056.
Failed to rescue degradation via pretreatment with lysosome inhibitor Chloroquine (HY-17589A).

Real Time qPCR[1]

Cell Line: NCI-H1944 SMARCA4-mutant nonsmall cell lung cancer cells
Concentration: 1, 10, 100 nM
Incubation Time: 18 h
Result: Induced a dose-dependent reduction in mRNA levels of SMARCA2 target genes KRT80 and PLAU, with significant decreases observed at concentrations ≥10 nM.
Parmacokinetics
Species Dose Route T1/2 Cmax AUC0-t Bioavailability C0 Vz CL AUC
Mice[1] 5 mg/kg i.v. 7.06 h / 12400 ng·h/mL / 7318 ng/mL 3.83 L/kg 6.27 mL/min/kg /
Mice[1] 15 mg/kg i.p. 18.85 h 2386 ng/mL 24391 ng·h/mL 65.5 % / / / /
Mice[1] 15 mg/kg p.o. 0.97 h 18 ng/mL 30 ng·h/mL 0.08 % / / / /
Rat[1] 5 mg/kg i.v. / / / / 6770 ng/mL / / 1667 ng·h/mL
Rat[1] 15 mg/kg i.p. / 672 ng/mL / 33 % / / / 2048 ng·h/mL
In Vivo

LJM133 (Compound 14) (50 mg/kg; i.v.; single dose) achieves durable in vivo target engagement, inducing robust degradation of SMARCA2 and PBRM1 in NCI-H1944 xenograft tumors for up to 48 hours[1].
LJM133 (25-50 mg/kg; i.v.; three times weekly; 18 days) exhibits robust, dose-dependent antitumor efficacy in NCI-H1944 xenograft models[1].

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

Animal Model: BALB/c nude mice with NCI-H1944 xenograft harboring a mutation in SMARCA4[1]
Dosage: 50 mg/kg
Administration: i.v.; single dose
Result: Induced robust degradation of SMARCA2 and PBRM1 in tumor tissues at 4 and 24 hours post-dose, with partial recovery detected at 48 hours.
Reached plasma concentrations of 3.9 μM at 4 hours, 0.6 μM at 24 hours, and 0.3 μM at 48 hours.
Achieved corresponding tumor concentrations of 1.6 μM at 4 hours, 0.5 μM at 24 hours, and 0.3 μM at 48 hours.
Animal Model: BALB/c nude mice with NCI-H1944 xenograft harboring a mutation in SMARCA4[1]
Dosage: 25 mg/kg; 50 mg/kg
Administration: i.v.; three times weekly; 18 days
Result: Induced dose-dependent tumor growth inhibition, with T/C values of 42.9% at 25 mg/kg and 24.0% at 50 mg/kg.
Achieved efficacy comparable to the reference PROTAC AU-15330 (HY-145388) at 50 mg/kg (T/C = 41.2%) at the 25 mg/kg dose.
Caused no significant body weight loss across treatment groups.
Induced near-complete degradation of SMARCA2 and PBRM1 in tumors at study termination for both 25 mg/kg and 50 mg/kg doses.
Molecular Weight

994.02

Formula

C51H58BrFN8O5S
SMILES

CC1=C(SC=N1)C2=CC=C(C=C2)[C@@H](NC([C@@H]3C[C@H](CN3C([C@H](C(C)(C)C)NC(C4(CC4)F)=O)=O)O)=O)CCCCCN5CCN(CC5)C6=CC=C7C=[N+]8[N-]C(C9=C(C=CC=C9C8=CC7=C6)Br)=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
References
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LJM133 Related Classifications

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Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

LJM133LJM 133LJM-133PROTACsSWI/SNF ComplexSWI/SNF Family of Chromatin-Remodelling Complexesxenograft modelSMARCA2NCI-H1975 cellsSMARCA4VHL E3 ligasenon-small cell lung cancerNCI-H1568 cellsNCI-H1944 cellsPBRM1proteasomeInhibitorinhibitorinhibit

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