K-975 |
Katalog-Nr.GC62132
One-Click Copy Product Info
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K-975 ist ein potenter, selektiver und oral aktiver TEAD-Inhibitor mit starker Hemmwirkung gegen Protein-Protein-Wechselwirkungen zwischen YAP1/TAZ und TEAD. K-975 bindet Über eine Acrylamidstruktur kovalent an Cys359, das sich in der Palmitat-Bindungstasche von TEAD befindet. K-975 zeigt AntitumoraktivitÄt bei malignem Pleuramesotheliom.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 2563855-03-6
Sample solution is provided at 25 µL, 10mM.
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K-975 is a potent and orally active inhibitor of YAP1/TAZ-TEAD protein-protein interaction[1]. Transcription enhancer-associated domain (TEAD) is a transcriptional activator of the Hippo pathway, which forms a complex with the transcriptional coactivator yes-associated protein (YAP) or the transcriptional coactivator PDZ-binding motif (TAZ), and their overactivation is associated with carcinogenesis[2]. K-975 showed effective antitumor effects in malignant pleural mesothelioma[3]. K-975 was able to attenuate the increase in connective tissue growth factor (CTGF) expression in retinal epithelial cells[4].
In vitro, K-975 (100nM) treatment of lentiviral-modified NCI-H2030 cells and NCI-H1792 cells for 24-72h resulted in a mild G1 phase arrest, and the combination with Adagrasib showed more significant effects than single drugs[5]. Treatment of NCI-H226 cells with K-975 (1-10000nM) for 24h reduced the expression of connective tissue growth factor (CTGF), insulin-like growth factor binding protein-3 (IGFBP3) and natriuretic peptide B (NPPB) mRNA, and increased the expression of F-box protein-32 (FBXO32) mRNA[6].
In vivo, oral administration of K-975 (100mg/kg) to treat human mesothelioma xenograft mice significantly inhibited tumor growth and improved survival in mice[6].
References:
[1] Bulakhova A, Cho J S, Rifkin J T, et al. Targeting the YAP/TAZ-TEAD pathway with TEAD inhibitors synergizes with chemotherapy and blocks diffuse gastric cancer progression[J]. Cancer Research, 2024, 84(6_Supplement): 7281-7281.
[2] Otsuki H, Uemori T, Inai Y, et al. Reversible and monitorable nephrotoxicity in rats by the novel potent transcriptional enhanced associate domain (TEAD) inhibitor, K-975[J]. The Journal of Toxicological Sciences, 2024, 49(4): 175-191.
[3] Kaneda A, Seike T, Uemori T, et al. Discovery of a first-in-class TEAD inhibitor which directly inhibits YAP/TAZ-TEAD protein-protein interaction and shows a potent anti-tumor effect in malignant pleural mesothelioma[J]. Cancer Research, 2019, 79(13_Supplement): 3086-3086.
[4] Murakami Y, Imaizumi T, Hashizume K, et al. Inhibition of Connective Tissue Growth Factor Expression in Adult Retinal Pigment Epithelial-19 Cells by Blocking Yes-Associated Protein/Transcriptional Coactivator with PDZ-Binding Motif Activity[J]. Journal of Ocular Pharmacology and Therapeutics, 2024, 40(4): 246-252.
[5] Tammaccaro S L, Prigent P, Le Bail J C, et al. TEAD inhibitors sensitize KRASG12C inhibitors via dual cell cycle arrest in KRASG12C-mutant NSCLC[J]. Pharmaceuticals, 2023, 16(4): 553.
[6] Kaneda A, Seike T, Danjo T, et al. The novel potent TEAD inhibitor, K-975, inhibits YAP1/TAZ-TEAD protein-protein interactions and exerts an anti-tumor effect on malignant pleural mesothelioma[J]. American Journal of Cancer Research, 2020, 10(12): 4399.
| Cell experiment [1]: | |
Cell lines | Lentivirus (Sartorius) modified NCI-H2030 (NCI-H2030-CC) and NCI-H1792 (NCI-H1792-CC) |
Preparation Method | Cell cycle analysis was performed using lentivirus (Sartorius) modified NCI-H2030 (NCI-H2030-CC) and NCI-H1792 (NCI-H1792-CC). The conditions analyzed were DMSO, 100nM of K-975, 30nM of adagrasib, and COMBO (selected doses of adagrasib and K-975). At least two biological replicates were analyzed for each condition at 24, 48, and 72h. Inhibitors of Aurora B kinase (SML0268) and PLK1 (RO-3280) were used as controls. |
Reaction Conditions | 100nM; 24, 48, 72h |
Applications | In a time-course experiment up to 72h, we observed that every single agent led to a slight arrest in the G1 phase post-treatment. The combination of adagrasib and K-975 showed more robust G1 phase arrest than single agents. |
| Animal experiment [2]: | |
Animal models | SCID mice |
Preparation Method | Mice were subcutaneously injected into the right flank with 5×106 NCI-H226 cells in PBS containing 50% (v/v) BD Matrigel basement membrane matrix or 5×106 MSTO-211H cells in PBS containing 50% (v/v) BD high-concentration Matrigel basement membrane matrix. When the tumor volumes reached 100-200mm3, mice were orally administered K-975 (100mg/kg, twice a day, daily) or palbociclib (150mg/kg, once a day, daily) alone or in combination. The tumor volumes and body weights of mice were measured every 3-4 days. |
Dosage form | 100mg/kg; twice a day; p.o. |
Applications | K-975 exerts an anti-tumor effect and significant survival benefit in human mesothelioma xenograft mice. K-975 suppressed the tumor growth in NCI-H226 and MSTO-211H xenograft models. |
References: | |
| Cas No. | 2563855-03-6 | SDF | |
| Formula | C16H14ClNO2 | M.Wt | 287.74 |
| Löslichkeit | DMSO : 220 mg/mL (764.58 mM; Need ultrasonic) | Storage | Store at -20°C, protect from light |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.4754 mL | 17.3768 mL | 34.7536 mL |
| 5 mM | 695.1 μL | 3.4754 mL | 6.9507 mL |
| 10 mM | 347.5 μL | 1.7377 mL | 3.4754 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
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Average Rating: 5 (Based on Reviews and 28 reference(s) in Google Scholar.)