MSC-4106 is a potent, orally bioavailable small molecule inhibitor of the YAP/TAZ-TEAD interaction. It functions by blocking the auto-palmitoylation of TEAD1 and TEAD3 transcription factors, and it has shown significant anti-tumor efficacy in the NCI-H226 mesothelioma xenograft model, supporting its use in cancer research.
Research Area
Stem Cell & Developmental Biology
Images & Validation
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Key Properties
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CAS Number
2738542-58-8
MW
359.3
Purity
>99.99% (May vary between batches)
Formula
C18H12F3N3O2
SMILES
Cn1cc2c3cc(ccc3n(-c3ccc(cc3)C(F)(F)F)c2n1)C(O)=O
Target
YAP
Solubility
DMSO:225 mg/mL (626.22 mM)
Bioactivity
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In Vivo
MSC-4106 (P.O.; 100 mg/kg once daily; 7 days) demonstrates anti-tumor effects with controlled tumor volume and good tolerability, maintaining stable body weight in mice . MSC-4106 (P.O.; 1, 5, 100 mg/kg once daily; 6, 24, 30, 48, and 72 h) down-regulates Cyr61 (cysteine-rich angiogenic inducer 61) expression, a TEAD-regulated target gene, in tumor lysates at all time points at 100 mg/kg and at 24 h at 5 mg/kg . Pharmacokinetic (PK) profiles in different species : - Mouse: Cl (0.2 l/h/kg), PO t 1/2 (45 h), PO AUC (45 μg h/mL), V ss (2 L/kg), F (>90%). - Rat: Cl (0.7 l/h/kg), PO t 1/2 (40 h), PO AUC (10 μg h/mL), V ss (5 L/kg), F (80%). - Dog: Cl (0.05 l/h/kg), PO t 1/2 (3.6 h), PO AUC (33 μg h/mL), V ss (0.3 L/kg), F (18%). Note: PO studies at 10 mg/kg; MSC-4106 formulated in 20% Kleptose in 50 mM PBS, pH 7.4. Animal model: NCI-H226 xenograft in H2d Rag2 female mice (9-week-old) . Dosage: 5, 100 mg/kg Oral gavage, once daily for 32 days, resulting in controlled tumor growth at 5 mg/kg and tumor regression at 100 mg/kg after 32 days of treatment.
In Vitro
MSC-4106, at a concentration of 10 μM, demonstrated notable effects in various assays related to cancer cell viability and interaction inhibition within a certain time frame. Specifically, after 24 hours of treatment, it significantly reduced the viability of SK-HEP-1 reporter and NCI-266 cells, with IC50 values measuring at 4 nM and 14 nM, respectively. Additionally, within 6 hours, it was observed to crystalize in the P-site of TEAD1, markedly inhibiting TEAD1 and TEAD3 palmitoylation in TEAD-overexpressing HEK293 cells by 97.3% and 75.9%, correspondingly. A four-day exposure to MSC-4106 also suggested its targeting action on TEAD through a diminished viability in NCI-H226 cells, indicative of its potential mechanistic pathways. Further evaluation via a Cell Viability Assay on NCI-H226 (YAP dependent) and SW620 YAP/TAZ KO (YAP-independent) cells exposed to varying concentrations of MSC-4106 for 96 hours revealed an inhibitory effect on NCI-H226 and a general cytotoxicity towards SW620 with an IC50 greater than 30 μM. Immunofluorescence studies in SK-HEP-1 cells after 24 hours of treatment confirmed the inhibition of YAP-TEAD interaction, showcasing MSC-4106’s multifaceted biochemical activities.
Storage & Handling
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Storage
-20°C
Expiration Date
12 months from date of receipt.
Disclaimer
For research use only
Alternative Names
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YAP–TEAD, MSC 4106, MSC4106, MSC-4106
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