TH-Z827 diTFA
Based on 1 Customer Validation
TH-Z827 diTFA is a selective KRASG12D inhibitor that exhibits activity against GDP-bound and GMPPNP-bound KRASG12D, but shows no activity against KRAS (WT) and KRASG12C. TH-Z827 diTFA blocks the KRASG12D-CRAF interaction with a IC50 value of 42 μM. TH-Z827 diTFA can be used for the research of pancreatic cancer.
Nur für Forschungszwecke. Wir verkaufen nicht an Patienten.
- Formel: C34H40F6N6O5
- Molecular Weight:726.71
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Speicherung:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biologische Aktivität
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Chemical Information
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Lösungsmittel & Löslichkeit
- Reinheit & Dokumentation
- Verweise
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Help & FAQs
Biologische Aktivität
Beschreibung
IC50 & Target
[1]|
KRas G12D 42 μM (IC50) |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
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| PANC-1 | IC50 |
4.4 μM
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Antiproliferative activity against KRAS(G12D)-mutant pancreatic cancer PANC-1 cells assessed as cell viability after 24 h incubation.
Antiproliferative activity against KRAS(G12D)-mutant pancreatic cancer PANC-1 cells assessed as cell viability after 24 h incubation.
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35075146 |
| HEK-293T | IC50 |
42 μM
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Inhibition of KRAS G12D-CRAF interaction in HEK 293T cells measured via split-luciferase reporter assay.
Inhibition of KRAS G12D-CRAF interaction in HEK 293T cells measured via split-luciferase reporter assay.
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35075146 |
In Vitro
TH-Z827 (10 min) diTFA potently inhibits SOS-catalyzed nucleotide exchange of GDP-bound KRASG12D with an IC50 of 3.1 μM, and displays nearly 10-fold selectivity for KRASG12D over KRASG12C[1].
TH-Z827 (800 μM) diTFA binds to both GDP-bound and GMPPNP-bound KRASG12D with similar affinities (Kd of 6.52 μM and 7.01 μM, respectively), and does not bind to KRASWT or KRASG12C[1].
TH-Z827 diTFA blocks the KRASG12D-CRAF interaction with an IC50 of 42 μM, without affecting interactions involving KRAS(WT) or KRASG12C[1].
TH-Z827 diTFA potently inhibits SOS-catalyzed GDP/GDP exchange of purified GDP-bound KRASG12D protein with an IC50 of 3.1 μM[2].
TH-Z827 diTFA exhibits selective binding and inhibition for purified KRASG12D protein over KRAS WT and KRASG12C proteins, with no measurable binding to the latter two variants[2].
TH-Z827 (24 h) diTFA inhibits proliferation of KRASG12D-mutant PANC-1 and Panc 04.03 pancreatic cancer cells with IC50 values of 4.4 μM and 4.7 μM, respectively[1].
TH-Z827 (1-20 μM; 3 h) diTFA inhibits MAPK and PI3K/mTOR signaling in KRASG12D-mutant PANC-1 and Panc 04.03 pancreatic cancer cells by reducing pERK and pAKT levels following 3 h of treatment[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. .
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Cell Line:KRAS(G12D)-mutant pancreatic cancer cell lines PANC-1 and Panc 04.03
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Concentration:1-20 μM
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Incubation Time:3 h
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Result:Reduced levels of phosphorylated ERK (pERK) in both PANC-1 and Panc 04.03 cells.
Reduced levels of phosphorylated AKT (pAKT) at Thr308 and Ser473 in both PANC-1 and Panc 04.03 cells.
Confirmed inhibition of MAPK and PI3K/mTOR signaling pathways.
In Vivo
TH-Z827 (10 mg/kg; i.p.) diTFA reduces pancreatic tumor volumes in C57BL/6 mice, and exhibits synergistic antitumor activity when combined with anti-PD-1 antibody[1].
TH-Z827 diTFA synergizes with an anti-PD-1 antibody to reduce tumor volume in C57BL/6 mice bearing KPC pancreatic cancer xenografts[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c nude mice[1]
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Dosage:10 mg/kg; 30 mg/kg
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Administration:i.p.; Days 38, 41, 44, 47, 50, 53, 56, 59, 62
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Result:Reduced final mean tumor volume to ~120 mm3 at 10 mg/kg dose compared to vehicle control.
Reduced final mean tumor volume to ~30 mm3 at 30 mg/kg dose compared to vehicle control.
Caused weight loss in mice at 30 mg/kg dose.
Chemical Information
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Appearance Solid
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Molecular Weight 726.71
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Formel C34H40F6N6O5
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SMILES
CC1=CC=CC2=C1C(N3CCC4=C(N=C(OC[C@H]5N(C)CCC5)N=C4N6[C@@H]7CNC[C@H]6CC7)C3)=CC=C2.FC(C(O)=O)(F)F.FC(C(O)=O)(F)F
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Versand
Room temperature in continental US; may vary elsewhere.
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Speicherung
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Lösungsmittel & Löslichkeit
In Vitro:
DMSO : 100 mg/mL (137.61 mM; Need ultrasonic; 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.
Konzentration (Stammlösung) × Volumen (Stammlösung) = Konzentration (Ziellösung) × Volumen (Ziellösung)
Reinheit & Dokumentation
Verweise
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 |
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| DMSO | 1 mM | 1.3761 mL | 6.8803 mL | 13.7606 mL | 34.4016 mL |
| 5 mM | 0.2752 mL | 1.3761 mL | 2.7521 mL | 6.8803 mL | |
| 10 mM | 0.1376 mL | 0.6880 mL | 1.3761 mL | 3.4402 mL | |
| 15 mM | 0.0917 mL | 0.4587 mL | 0.9174 mL | 2.2934 mL | |
| 20 mM | 0.0688 mL | 0.3440 mL | 0.6880 mL | 1.7201 mL | |
| 25 mM | 0.0550 mL | 0.2752 mL | 0.5504 mL | 1.3761 mL | |
| 30 mM | 0.0459 mL | 0.2293 mL | 0.4587 mL | 1.1467 mL | |
| 40 mM | 0.0344 mL | 0.1720 mL | 0.3440 mL | 0.8600 mL | |
| 50 mM | 0.0275 mL | 0.1376 mL | 0.2752 mL | 0.6880 mL | |
| 60 mM | 0.0229 mL | 0.1147 mL | 0.2293 mL | 0.5734 mL | |
| 80 mM | 0.0172 mL | 0.0860 mL | 0.1720 mL | 0.4300 mL | |
| 100 mM | 0.0138 mL | 0.0688 mL | 0.1376 mL | 0.3440 mL |
TH-Z827 diTFA Related Classifications
HY-153663B Related Classifications
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