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.
For research use only. We do not sell to patients.
- Formula: C34H40F6N6O5
- Molecular Weight:726.71
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Storage:
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]
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
IC50 & Target
[1]|
KRas G12D 42 μM (IC50) |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| 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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Molecular Weight 726.71
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Formula 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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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Solvent & Solubility
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)
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Purity & Documentation
References
Complete Stock Solution Preparation Table
| 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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