TH-Z827
TH-Z827 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 blocks the KRASG12D-CRAF interaction with a IC50 value of 42 μM. TH-Z827 can be used for the research of pancreatic cancer.
For research use only. We do not sell to patients.
- Purity : 95.12%
- CAS No.: 2847881-81-4
- Formula: C30H38N6O
- Molecular Weight:498.66
-
Storage: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]
-
Biological Activity
-
Chemical Information
-
Solvent & Solubility
- Purity & Documentation
- References
-
Help & FAQs
Biological Activity
Description
IC50 & Target
[1]|
KRas G12D 42 μM (IC50) |
In Vitro
TH-Z827 (10 min) 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) 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 blocks the KRASG12D-CRAF interaction with an IC50 of 42 μM, without affecting interactions involving KRAS(WT) or KRASG12C[1].
TH-Z827 potently inhibits SOS-catalyzed GDP/GDP exchange of purified GDP-bound KRASG12D protein with an IC50 of 3.1 μM[2].
TH-Z827 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) 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) 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.
-
Cell Line:KRAS(G12D)-mutant pancreatic cancer cell lines PANC-1 and Panc 04.03
-
Concentration:1-20 μM
-
Incubation Time:3 h
-
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.) reduces pancreatic tumor volumes in C57BL/6 mice, and exhibits synergistic antitumor activity when combined with anti-PD-1 antibody[1].
TH-Z827 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.
-
Animal Model:BALB/c nude mice[1]
-
Dosage:10 mg/kg; 30 mg/kg
-
Administration:i.p.; Days 38, 41, 44, 47, 50, 53, 56, 59, 62
-
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
-
CAS No. 2847881-81-4
-
Appearance Solid
-
Molecular Weight 498.66
-
Formula C30H38N6O
-
Color White to off-white
-
SMILES
CN(CCC1)[C@@H]1COC2=NC(N3[C@@H]4CNC[C@H]3CC4)=C5C(CN(C6=CC=CC7=C6C(C)=CC=C7)CC5)=N2
-
Shipping
Room temperature in continental US; may vary elsewhere.
-
Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvent & Solubility
In Vitro:
DMSO : 100 mg/mL (200.54 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.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Purity & Documentation
-
Data Sheet (289 KB)
-
SDS (251 KB)
- English - EN (251 KB)
- Français - FR (251 KB)
- Deutsch - DE (251 KB)
- Norwegian - NO (251 KB)
- Español - ES (251 KB)
- Swedish - SV (251 KB)
- Italian - IT (251 KB)
- Korean - KR (251 KB)
- Portuguese - PT (251 KB)
-
Handling Instructions (2659 KB)
References
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 |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.0054 mL | 10.0269 mL | 20.0537 mL | 50.1344 mL |
| 5 mM | 0.4011 mL | 2.0054 mL | 4.0107 mL | 10.0269 mL | |
| 10 mM | 0.2005 mL | 1.0027 mL | 2.0054 mL | 5.0134 mL | |
| 15 mM | 0.1337 mL | 0.6685 mL | 1.3369 mL | 3.3423 mL | |
| 20 mM | 0.1003 mL | 0.5013 mL | 1.0027 mL | 2.5067 mL | |
| 25 mM | 0.0802 mL | 0.4011 mL | 0.8021 mL | 2.0054 mL | |
| 30 mM | 0.0668 mL | 0.3342 mL | 0.6685 mL | 1.6711 mL | |
| 40 mM | 0.0501 mL | 0.2507 mL | 0.5013 mL | 1.2534 mL | |
| 50 mM | 0.0401 mL | 0.2005 mL | 0.4011 mL | 1.0027 mL | |
| 60 mM | 0.0334 mL | 0.1671 mL | 0.3342 mL | 0.8356 mL | |
| 80 mM | 0.0251 mL | 0.1253 mL | 0.2507 mL | 0.6267 mL | |
| 100 mM | 0.0201 mL | 0.1003 mL | 0.2005 mL | 0.5013 mL |
TH-Z827 Related Classifications
HY-153663 Related Classifications
Powered by Bioz