LG-NE-29
LG-NE-29 is an orally active, selective GSPT1 and GSPT2 Molecular glue degrader with DC50 values of 7 nM and 3 nM, respectively. LG-NE-29 mediates CRBN-dependent ubiquitination and proteasomal degradation of GSPT1/2. LG-NE-29 activates the integrated stress response and induces intrinsic Apoptosis. LG-NE-29 exerts anticancer activity against glioblastoma.
For research use only. We do not sell to patients.
- Formula: C27H21F2N3O6
- Molecular Weight:521.47
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- Protocols
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All Eukaryotic Release Factor (eRF) Isoforms
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Biological Activity
Description
LG-NE-29 is an orally active, selective GSPT1 and GSPT2 Molecular glue degrader with DC50 values of 7 nM and 3 nM, respectively. LG-NE-29 mediates CRBN-dependent ubiquitination and proteasomal degradation of GSPT1/2. LG-NE-29 activates the integrated stress response and induces intrinsic Apoptosis. LG-NE-29 exerts anticancer activity against glioblastoma[1].
IC50 & Target
[1]|
eRF3a/GSPT1 7 nM (DC50) |
eRF3b/GSPT2 3 nM (DC50) |
CRBN |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| MOLT-4 | DC50 |
1.5 nM
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GSPT1 degradation in MOLT-4 HiBiT-GSPT1 reporter cells assessed by Nano-Glo HiBiT Lytic Assay after 6 hrs incubation.
GSPT1 degradation in MOLT-4 HiBiT-GSPT1 reporter cells assessed by Nano-Glo HiBiT Lytic Assay after 6 hrs incubation.
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42911697 |
| MOLT-4 | DC50 |
10 nM
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GSPT1 degradation in MOLT-4 HiBiT-GSPT1 reporter cells assessed by Nano-Glo HiBiT Lytic Assay after 16 hrs incubation with DC50 less than 10 nM.
GSPT1 degradation in MOLT-4 HiBiT-GSPT1 reporter cells assessed by Nano-Glo HiBiT Lytic Assay after 16 hrs incubation with DC50 less than 10 nM.
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42911697 |
| U-251 | IC50 |
61 nM
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Antiproliferative activity against U251MG glioma cells assessed as viability reduction after 72 hrs incubation.
Antiproliferative activity against U251MG glioma cells assessed as viability reduction after 72 hrs incubation.
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42911697 |
| T98G | IC50 |
10000 nM
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Antiproliferative activity against T98G glioma cells assessed as viability reduction after 72 hrs incubation with IC50 greater than 10,000 nM.
Antiproliferative activity against T98G glioma cells assessed as viability reduction after 72 hrs incubation with IC50 greater than 10,000 nM.
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42911697 |
| A 172 | IC50 |
95 nM
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Antiproliferative activity against A172 glioma cells assessed as viability reduction after 72 hrs incubation.
Antiproliferative activity against A172 glioma cells assessed as viability reduction after 72 hrs incubation.
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42911697 |
| U-87MG ATCC | IC50 |
14 nM
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Antiproliferative activity against U87MG glioma cells assessed as viability reduction after 72 hrs incubation.
Antiproliferative activity against U87MG glioma cells assessed as viability reduction after 72 hrs incubation.
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42911697 |
| U-118-MG | IC50 |
10000 nM
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Antiproliferative activity against U118MG glioma cells assessed as viability reduction after 72 hrs incubation with IC50 greater than 10,000 nM.
Antiproliferative activity against U118MG glioma cells assessed as viability reduction after 72 hrs incubation with IC50 greater than 10,000 nM.
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42911697 |
| BV-2 | IC50 |
10000 nM
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Antiproliferative activity against BV2 microglia assessed as viability reduction after 72 hrs incubation with IC50 greater than 10,000 nM.
Antiproliferative activity against BV2 microglia assessed as viability reduction after 72 hrs incubation with IC50 greater than 10,000 nM.
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42911697 |
| HEK-293T | IC50 |
33 nM
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Antiproliferative activity against wild-type 293T cells assessed as viability reduction after 48 hrs incubation.
Antiproliferative activity against wild-type 293T cells assessed as viability reduction after 48 hrs incubation.
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42911697 |
In Vitro
Anti-cancerProtein/Amino Acid MetabolismOthers
Anti-cancer
Anti-cancer
Protein/Amino Acid Metabolism
LG-NE-29 (0.01-10 µM; 8 h) dose-dependently degrades endogenous GSPT1 in U87MG cells[1].
Protein/Amino Acid Metabolism
LG-NE-29 (10 µM; 6-16 h) is a potent GSPT1 degrader in MOLT4-HiBiT-GSPT1 cells, with DC50 = 1.5 nM at 6 h[1].
LG-NE-29 (1 µM; 6 h) selectively downregulates GSPT1 and GSPT2 in MOLT-4 cells without depleting IKZF1/3 or other CRBN neosubstrates[1].
LG-NE-29 dual-degrades GSPT1 and GSPT2, with DC50 values of 7 nM and 3 nM, respectively[1].
LG-NE-29 (1 µM; 0.5-8 h) rapidly depletes GSPT1 in U87MG cells, with detectable degradation within 4 h[1].
LG-NE-29 (1 µM; 6 h) selectively downregulates GSPT1 and GSPT2 in MOLT-4 cells without depleting IKZF1/3 or other CRBN neosubstrates[1].
LG-NE-29 dual-degrades GSPT1 and GSPT2, with DC50 values of 7 nM and 3 nM, respectively[1].
LG-NE-29 (1 µM; 0.5-8 h) rapidly depletes GSPT1 in U87MG cells, with detectable degradation within 4 h[1].
Others
LG-NE-29 (1 µM; 0-60 min) is metabolically stable in MLM, with T1/2 > 60 min[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Viability Assay[1]
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Cell Line:Glioma cell lines and BV2 microglia
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Concentration:10 µM (Imax)
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Incubation Time:72 h
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Result:TR-U251: IC50 = 42 nM, Imax = 80%.
U251MG: IC50 = 61 nM, Imax = 66%.
T98G: IC50 > 10,000 nM, Imax = 48%.
A172: IC50 = 95 nM, Imax = 66%.
U87MG: IC50 = 14 nM, Imax = 80%.
U118MG: IC50 > 10,000 nM, Imax = 10%.
BV2: IC50 > 10,000 nM, Imax = 0%.
Western Blot Analysis[1]
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Cell Line:U87MG glioblastoma cells
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Concentration:10, 1, 0.1, and 0.01 µM
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Incubation Time:8 h
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Result:Robust, dose-dependent degradation of endogenous GSPT1 occurred.
Western Blot Analysis[1]
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Cell Line:U87MG cells
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Concentration:1 µM
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Incubation Time:0.5, 2, 4, 6, and 8 h
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Result:Rapid target depletion occurred.
GSPT1 degradation was detectable within 4 h.
Parmacokinetics
In Vivo
Anti-cancerProtein/Amino Acid Metabolism
Anti-cancer
LG-NE-29 (5-20 mg/kg; p.o.; once daily for 13 days) produces dose-dependent tumor growth inhibition in U87MG glioblastoma xenografts, with 64.98% TGI at 20 mg/kg[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c nude (female, 6-8 weeks old)[1]
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Dosage:1 mg/kg; 5 mg/kg; 20 mg/kg
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Administration:p.o.; single dose
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Result:At 5 h post-dose, GSPT1 was partially reduced at 5 mg/kg and near-completely depleted at 20 mg/kg.
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Animal Model:BALB/c nude (female, 6-8 weeks old)[1]
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Dosage:5 mg/kg; 20 mg/kg
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Administration:p.o.; once daily for 13 days (Results text states 14 days)
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Result:Produced dose-dependent tumor growth inhibition: 43.18% at 5 mg/kg and 64.98% at 20 mg/kg (also reported as 65% at 20 mg/kg).
Terminal tumor immunoblot showed sustained, dose-dependent GSPT1 degradation and increased ATF4 and CHOP; cleaved caspase-3 was also upregulated.
Ki-67 staining index was reduced in the 20 mg/kg group versus vehicle.
Chemical Information
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Molecular Weight 521.47
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Formula C27H21F2N3O6
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SMILES
O=C(CCC1N(C2=O)CC3=C2C=C(C=C3)COC(NC4=CC=C(C=C4)OC5=CC=C(C(F)=C5)F)=O)NC1=O
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Shipping
Room temperature in continental US; may vary elsewhere.
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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%
References
Calculators
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LG-NE-29 Related Classifications
HY-190990 Related Classifications
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Keywords
- LG-NE-29
- Molecular Glues
- Eukaryotic Release Factor (eRF)
- Apoptosis
- E1/E2/E3 Enzyme
- E1 activating enzyme
- E2 conjugating enzyme
- E3 ligating enzyme
- Ubiquitin activating enzyme
- Ubiquitin conjugating enzyme
- Ubiquitin ligase
- CRBN
- GSPT1
- GSPT2
- glioblastoma
- glioma organoids
- integrated stress response
- intrinsic apoptosis
- proteasomal degradation
- temozolomide resistance
- ubiquitination
- Inhibitor
- inhibitor
- inhibit