MC-ND-18
MC-ND-18 is an ATTEC degrader that degrades NLRP3 via the Autophagy pathway, with a DC50 of 125.5 nM in THP-1 cells. MC-ND-18 exhibits anti-inflammatory activity in a DSS-induced mouse model of colitis. MC-ND-18 can be used for research on inflammatory bowel disease. MC-ND-18 consists of an NLRP3 inhibitor (HY-156121), a linker (HY-W018745), and an LC3 ligand.
Para uso exclusivo en investigación. No vendemos a pacientes.
- No. CAS: 3081572-53-1
- Fòrmula: C42H42Br2IN3O9S
- Peso molecular:1051.58
-
Almacenamiento:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
-
Actividad biológica
-
Chemical Information
- Pureza y Documentación
- Referencias
-
Help & FAQs
Actividad biológica
|
NLRP3 125.5 nM (DC50) |
MC-ND-18 (100-200 nM; 24 h) potently inhibits IL-1β secretion in PMA-differentiated THP-1 cells, with an inhibition rate of 73.6% at 200 nM and 45.8% at 100 nM[1].
MC-ND-18 (100-500 nM; 24 h) induces concentration-dependent degradation of NLRP3 in PMA-differentiated THP-1 cells, with degradation rates of 65% at 500 nM, 49% at 200 nM, and 13% at 100 nM[1].
MC-ND-18 (50 nM-1 μM; 24 h) induces NLRP3 degradation in PMA-differentiated THP-1 cells, with a DC50 of 125.5 nM, and the maximum degradation rate reaches up to 70% at 500 nM[1].
MC-ND-18 (50 nM-5 μM; 24 h) exhibits low cytotoxicity in PMA-differentiated THP-1 cells, and no significant reduction in relative cell viability is observed after incubation at concentrations ranging from 50 nM to 5 μM for 24 h[1].
MC-ND-18 (19.5 nM-5 μM) binds to purified NLRP3 protein lacking the LRR domain and LC3B protein, with Kd values of 0.929 μM and 3.548 μM, respectively, indicating that it exhibits concentration-dependent affinity for both targets[1].
MC-ND-18 (24 h) does not degrade NLRP3 in PMA-differentiated THP-1 cells via the proteasomal pathway, as combined treatment with the proteasome inhibitor MG132 does not attenuate its degrading activity[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Cell Line:PMA-differentiated THP-1 cells
-
Concentration:100 nM, 200 nM
-
Incubation Time:24 h (co-incubation with LPS)
-
Result:Inhibited IL-1β secretion by 45.8 % at 100 nM.
Inhibited IL-1β secretion by 73.6 % at 200 nM.
-
Cell Line:PMA-differentiated THP-1 cells
-
Concentration:100 nM, 200 nM, 500 nM
-
Incubation Time:24 h (co-incubation with LPS)
-
Result:Degraded NLRP3 by 13 % at 100 nM.
Degraded NLRP3 by 49 % at 200 nM.
Degraded NLRP3 by 65 % at 500 nM.
-
Cell Line:PMA-differentiated THP-1 cells
-
Concentration:50 nM, 100 nM, 200 nM, 500 nM, 1000 nM
-
Incubation Time:24 h (co-incubation with LPS)
-
Result:Exhibited a concentration-dependent NLRP3 degradation profile from 50 nM to 500 nM.
Achieved a maximum degradation rate of 70 % at 500 nM.
Had a DC50 for NLRP3 degradation of 125.5 nM.
Showed reduced degradation efficiency at 1000 nM, consistent with a "hook effect" for bifunctional molecules.
-
Cell Line:THP-1 cells
-
Concentration:500 nM
-
Incubation Time:4 h
-
Result:Resulted in substantial colocalization of NLRP3 and LC3B, with a Pearson correlation coefficient of 0.53.
MC-ND-18 (20 mg/kg; i.p.; daily) fails to alleviate DSS-induced colitis in NLRP3KO mice, confirming its therapeutic effects are dependent on the NLRP3 pathway[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Animal Model:C57BL/6 (group size n=5 per cohort)[1]
-
Dosage:5 mg/kg; 20 mg/kg
-
Administration:i.p.; daily
-
Result:Reduced weight loss and dose-dependent suppression of DAI increase compared to the model group.
Mitigated colon shortening relative to the model group.
Markedly reduced intestinal mucosal damage, inflammatory cell infiltration, and loss of intestinal crypts compared to the model group.
Significantly reduced colonic NLRP3 and IL-1β protein levels compared to the model group.
-
Animal Model:C57BL/6-NLRP3KO (group size n=3 per cohort)[1]
-
Dosage:20 mg/kg
-
Administration:i.p.; daily
-
Result:Did not reduce body weight loss, suppress DAI increase, or mitigate colon shortening compared to the model group.
Showed no significant improvement in intestinal mucosal damage, inflammatory cell infiltration, or intestinal crypt loss compared to the model group.
Did not reduce colonic IL-1β levels compared to the model group; NLRP3 protein was undetectable in all cohorts.
Chemical Information
-
No. CAS 3081572-53-1
-
Peso molecular 1051.58
-
Fòrmula C42H42Br2IN3O9S
-
SMILES
IC1=CC=C(C(/C(C2=O)=C/C3=CC(Br)=C(O)C(Br)=C3)=C1)N2CCOCCOCCOCCOC4=CC=C(S(NC(NC5=C6C(CCC6)=CC7=C5CCC7)=O)(=O)=O)C=C4
-
Envío
Room temperature in continental US; may vary elsewhere.
-
Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
-
Ficha de datos (275 KB)
-
SDS (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)
-
Instrucciones de manejo (2659 KB)
Referencias
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
MC-ND-18 Related Classifications
HY-162588 Related Classifications
Powered by Bioz