| Size | Price | Stock | Qty |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg | |||
| Other Sizes |
| Targets |
TEAD2 (IC50 = 710 nM); TEAD4 (IC50 = 672 nM)
MGH-CP1 targets TEAD2 and TEAD4, transcription factors that are key effectors of the Hippo signaling pathway. TEAD proteins undergo autopalmitoylation at a conserved cysteine residue, which is required for their transcriptional activity and interaction with coactivators such as YAP and TAZ. By inhibiting TEAD autopalmitoylation with IC₅₀ values of 710 nM (TEAD2) and 672 nM (TEAD4), MGH-CP1 reduces TEAD transcriptional activity. This places the compound within the Hippo signaling pathway, which is involved in organ size control, tissue homeostasis, and cancer. |
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| ln Vitro |
In vitro, MGH-CP1 shows a dose-dependent and strong inhibition of TEAD2/4 auto-palmitoylation. Treatment with MGH-CP1 significantly lowers the levels of palmitoylation of native or ectopically expressed TEAD proteins in cells. MGH-CP1 is selective for TEADs because it has no effect on the auto-palmitoylation of a number of palmitoyl acyltransferases from the ZDHHC family. By directly focusing on TEAD auto-palmitoylation, MGH-CP1 is a selective small-molecule pan-TEAD inhibitor. [1]
In vitro, MGH-CP1 demonstrates potent and selective inhibition of TEAD palmitoylation. The compound exhibits dose-dependent inhibition of TEAD2/4 auto-palmitoylation with IC₅₀ values of 710 nM and 672 nM, respectively. MGH-CP1 reduces the palmitoylation levels of endogenous or ectopically expressed TEAD proteins in cells. It can decrease TEAD transcriptional activity and downstream target gene expression. The compound is used as a research tool to study the Hippo signaling pathway and its role in cancer and other diseases. |
| ln Vivo |
In vivo, MGH-CP1 reduces TEAD activity in the intestine of Lats1/2 KO mice. The palmitoylation of TEAD proteins in the intestinal epithelium can be effectively inhibited by MGH-CP1. After two weeks of treatment, MGH-CP1 is well tolerated and appears to have no negative effects on the general health or body weight of the animal. The TEAD target genes CTGF and ANKRD1 are effectively inhibited by MGH-CP1 treatment in Lats1/2 KO intestine, in contrast to its apparent lack of effect in wild-type intestine.[1]
In vivo, MGH-CP1 is orally bioactive. The compound has been shown to inhibit TEAD activity and downstream signaling in animal models. By blocking TEAD palmitoylation, MGH-CP1 reduces YAP/TAZ-mediated transcription, which is implicated in tumor growth and progression. The compound may have potential for cancer therapy, particularly in tumors with activated Hippo signaling. Further in vivo studies are needed to fully characterize its efficacy and safety profile. |
| Enzyme Assay |
In vitro enzyme assays for MGH-CP1 involve measuring TEAD autopalmitoylation activity. The standard protocol includes incubating recombinant TEAD2 or TEAD4 proteins with palmitoyl-CoA and varying concentrations of MGH-CP1 (0.01-100 µM). Palmitoylation is detected by autoradiography using [³H]-palmitoyl-CoA or by acyl-biotin exchange chemistry followed by western blot. IC₅₀ values are calculated from dose-response curves. The selectivity of MGH-CP1 for TEAD2 and TEAD4 over other TEAD family members is assessed.
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| Cell Assay |
In DMEM supplemented with 10% FBS and 1% penicillin/streptomycin, HEK293T cells, Lats1/2 conditional MEFs, and MDA-MB-231 cells are cultured. Prior to the next experiment, Lats1/2 is deleted in Lats1/2 conditional MEFs carrying CMV-CreER by incubating the cells with 4-OH Tamoxifen (2.5 mM) in DMEM for 4 days. Lipofectamine 2000 is used for transfection in HEK293T cells. For luciferase reporter assays, HEK293T cells are transfected with the expression vectors of the following proteins: pCIG-Wnt3a, pCMV-LRP5C, pCIG-BMP4, pCIG-Gli1, pGIPZ-IKBKE, and pCMV-Renilla lucifease. Using the dual-lucif-erase reporter kit, luciferase activities are detected 24 hours after transfection in cells treated with or without Wnt3A, LiCl, or MGH-CP1.
Cell-based assays for MGH-CP1 are conducted in cancer cell lines or cells expressing TEAD proteins. Cells are treated with MGH-CP1 at concentrations ranging from 0.1-100 µM for 24-72 hours. TEAD palmitoylation levels are assessed by acyl-biotin exchange chemistry followed by western blot or by immunoprecipitation. TEAD transcriptional activity is measured using luciferase reporter assays with TEAD-responsive promoters. Expression of TEAD target genes (e.g., CTGF, CYR61) is analyzed by qPCR. Cell proliferation and viability are assessed by MTT or CellTiter-Glo assays. |
| Animal Protocol |
In vivo animal experiments for MGH-CP1 typically use mouse xenograft or syngeneic tumor models. Animals are administered MGH-CP1 via oral gavage at doses of 1-100 mg/kg. Tumor volume is measured periodically, and body weight is monitored. At study termination, tumors and tissues are collected for analysis of TEAD palmitoylation, transcriptional activity, and downstream signaling. Pharmacokinetic studies are performed to determine oral bioavailability and exposure. The compound's effects on tumor growth and progression are evaluated.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for MGH-CP1 show that it is orally bioactive. As a small molecule with a molecular weight of 368.50 g/mol, the compound is expected to have moderate oral bioavailability and tissue distribution. Solubility is in DMSO. Storage: typically at -20°C. Purity is typically ≥98%. The compound is a potent and selective TEAD palmitoylation inhibitor used for research on the Hippo signaling pathway.
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| Toxicity/Toxicokinetics |
MGH-CP1 is supplied for research use only and is not intended for human administration. Toxicity data are limited, but the compound is reported to be orally bioactive with acceptable tolerability in preclinical studies. Standard laboratory safety precautions should be followed. No specific toxicological studies have been published. The compound should be handled with care and stored appropriately.
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| References | |
| Additional Infomation |
MGH-CP1 (CAS 896657-58-2) is a research compound supplied for laboratory use only. It is not an approved drug and has no clinical trial or marketing authorization status. The compound is a potent and selective inhibitor of TEAD palmitoylation with IC₅₀ values of 710 nM for TEAD2 and 672 nM for TEAD4. It is orally bioactive and used for research on the Hippo signaling pathway. Purity is typically ≥98% and the compound is soluble in DMSO.
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| Molecular Formula |
C20H24N4OS
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|---|---|
| Molecular Weight |
368.495762825012
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| Exact Mass |
368.167
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| Elemental Analysis |
C, 65.19; H, 6.57; N, 15.20; O, 4.34; S, 8.70
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| CAS # |
896657-58-2
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| Related CAS # |
896657-58-2
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| PubChem CID |
2993112
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Index of Refraction |
1.664
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| LogP |
4.65
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
26
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| Complexity |
493
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(CSC1NC=NN=1)NC1C=CC(C23CC4CC(C2)CC(C4)C3)=CC=1
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| InChi Key |
UUKXOVBCMOZQNC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H24N4OS/c25-18(11-26-19-21-12-22-24-19)23-17-3-1-16(2-4-17)20-8-13-5-14(9-20)7-15(6-13)10-20/h1-4,12-15H,5-11H2,(H,23,25)(H,21,22,24)
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| Chemical Name |
N-[4-(1-adamantyl)phenyl]-2-(1H-1,2,4-triazol-5-ylsulfanyl)acetamide
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| Synonyms |
MGH CP1; MGH-CP1; MGHCP1
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 74~100 mg/mL (200.8~271.4 mM)
Ethanol: ~74 mg/mL (~200.8 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.78 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.78 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.78 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7137 mL | 13.5685 mL | 27.1370 mL | |
| 5 mM | 0.5427 mL | 2.7137 mL | 5.4274 mL | |
| 10 mM | 0.2714 mL | 1.3569 mL | 2.7137 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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