KMG-1068
Based on 1 Customer Validation
KMG-1068 is a molecular glue degrader that induces proteasomal degradation of GSPT1 and GSPT2 with DC50 values of 126.7 nM and 42.2 nM, respectively. KMG-1068 binds to the C-terminal IMiD-binding site of CRBN, forms ternary complexes with GSPT1 and GSPT2, and mediates proteasomal degradation of target proteins via the CRL4 ubiquitination pathway. KMG-1068 is applicable to research related to acute myeloid leukemia.
For research use only. We do not sell to patients.
- Purity: 99.73%
- CAS No.: 3113750-79-8
- Formula: C21H22N4O4S
- Molecular Weight:426.49
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Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
KMG-1068 (compound 4a) (serial concentrations; 72 h) potently inhibits the proliferation of HEK293T, Jurkat and various solid tumor cell lines in a Cullin-RING ligase-dependent manner, with a GI50 range of 0.2 μM to 0.8 μM in the absence of MLN4924[1].
KMG-1068 (72 h) exerts antiproliferative effects on HEK293T cells in a CUL4-dependent manner, and the GI50 value rises by 4-fold in CUL4-knockdown cells relative to control cells, which verifies this regulatory relationship[1].
KMG-1068 forms a ternary complex with CRBN and GSPT1 in HEK293T cells, with an EC50 of 11.4 μM; it induces proximity-dependent interaction between CRBN and GSPT1/2 in Mia-paca2 cells[1].
KMG-1068 (0-10 μM; 6 h) induces dose-dependent degradation of GSPT1 and GSPT2 in Jurkat cells, with DC50 values of 126.7 nM and 42.2 nM, respectively; this degradation is proteasome-dependent[1].
KMG-1068 (1 μM; 6 h) induces GSPT1 degradation in HEK293T cells, and this degradation effect relies on CUL4-containing Cullin-RING ligase complex[1].
KMG-1068 (0-10 μM; 24 h) triggers GSPT1 degradation in MEF cells, and this degradation relies on binding to CRBN's tryptophan triad pocket; the effect is totally lost in cells with CRBNW386A mutant[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Jurkat cells
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Concentration:0.01, 0.03, 0.1, 0.3, 1, 3, 10 μM
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Incubation Time:6 h
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Result:Induced dose-dependent degradation of GSPT1 and GSPT2, with DC50 values of 126.7 nM for GSPT1 and 42.2 nM for GSPT2.
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Cell Line:Jurkat cells
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Concentration:0, 0.1, 1, 10 μM (KMG-1068); 1 μM (bortezomib, co-treated)
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Incubation Time:6 h
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Result:Induced degradation of GSPT1 and GSPT2 was blocked by co-treatment with the proteasome inhibitor bortezomib.
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Cell Line:HEK293T Cullin knockdown cell lines
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Concentration:1 μM
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Incubation Time:6 h
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Result:Induced GSPT1 degradation was abolished exclusively in CUL4 knockdown cells, while degradation remained intact in cells with knockdown of other Cullin family members.
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Cell Line:wild-type and CRBN knockout Jurkat cells
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Concentration:0, 0.1, 1, 10 μM
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Incubation Time:6 h
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Result:Induced degradation of GSPT1 and GSPT2 was completely abrogated in CRBN knockout Jurkat cells, while degradation was observed in wild-type cells.
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Cell Line:MEF mCRBN knockout cells expressing human wild-type CRBN or CRBN W386A mutant
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Concentration:0, 0.1, 1, 10 μM
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Incubation Time:24 h
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Result:Induced dose-dependent GSPT1 degradation in cells expressing wild-type human CRBN, but degradation activity was markedly reduced in cells expressing the CRBN W386A mutant.
Chemical Information
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CAS No. 3113750-79-8
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Appearance Solid
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Molecular Weight 426.49
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Formula C21H22N4O4S
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Color White to off-white
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SMILES
O=C1C(C)=C(C)N=CN1CC(NC2=NC(C(OC)=O)=C(CCC3=CC=CC=C3)S2)=O
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvent & Solubility
DMSO : 3.33 mg/mL (7.81 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Purity & Documentation
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Data Sheet (278 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Handling Instructions (2659 KB)
References
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.3447 mL | 11.7236 mL | 23.4472 mL | 58.6180 mL |
| 5 mM | 0.4689 mL | 2.3447 mL | 4.6894 mL | 11.7236 mL |
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