MRTX1133 |
Catalog No.GC62699
One-Click Copy Product Info
|
MRTX1133 es un inhibidor de KRASG12D excepcionalmente potente y selectivo con alta afinidad (<2nM).
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 2621928-55-8
Sample solution is provided at 25 µL, 10mM.
_1-3.$$$39978408@51.jpg');)
_1-9.$$$38538795@65.jpg');)
_1-9.$$$39112701@51.jpg');)
_1-7.$$$37316672@70.jpg');)
_366-372.$$$36198801@70.jpg');)
.$$$38565142@65.jpg');)
_1867-1883.$$$33248023@67.jpg');)
_eads6055.$$$39977546@45.jpg');)
_eadm9805.$$$40080571@45.jpg');)
_eadj3020.$$$39666821@45.jpg');)
_1-20.$$$39757301@28.jpg');)
_1-24.$$$38898113@28.jpg');)
_273-287.$$$36806353@46.jpg');)
_1-16.$$$37156877@44.jpg');)
_1-19.$$$37460805@44.jpg');)
_1291-1307.$$$34518654@46.jpg');)
MRTX1133 es un inhibidor de KRASG12D excepcionalmente potente y selectivo con alta afinidad (<2nM).[1]
In vitro, en la línea celular AGS, MRTX1133 inhibió la fosforilación de ERK con un IC50 de 2 nM. Mientras tanto, MRTX1133 actuó contra la misma línea celular con un IC50 de 6 nM en un ensayo de viabilidad 2D.[1] En la prueba de eficacia in vitro, en células HPAC mutantes KRASG12D, se indicó que el tratamiento con 0,05 nM - 300 nM de MRTX1133 modula pERK, pS6 y DUSP6 de manera dependiente de la dosis.[2]
In vivo, el experimento mostró que el tratamiento con 30 mg/kg de MRTX1133 por vía intraperitoneal en ratones CD-1 causó una exposición plasmática sostenida que superó el valor de IC50 ajustado por la fracción libre de pERK en la línea celular mutante KRASG12D Panc 04.03 durante aproximadamente 8 horas. Y en el modelo de tumor xenoinjertado Panc 04.03, se sugirió que MRTX1133 (3-30 mg/kg, i.p.) tiene una actividad antitumoral dependiente de la dosis con una inhibición del crecimiento del 94% observada a 3 mg/kg BID (IP) y regresiones tumorales de -62% y -73% observadas a 10 y 30 mg/kg BID (IP), respectivamente.[1]
References:
[1].Wang X, Allen S, et al. Identification of MRTX1133, a Noncovalent, Potent, and Selective KRASG12D Inhibitor. J Med Chem. 2022 Feb 24;65(4):3123-3133.
[2].Swiatnicki M, Engel L, Shrestha R, Alves J, Goueli SA, Zegzouti H. Profiling oncogenic KRAS mutant drugs with a cell-based Lumit p-ERK immunoassay. SLAS Discov. 2022 Jun;27(4):249-257.
| Cell experiment [1]: | |
|
Cell lines |
KRAS G12D mutant LS513 cells |
|
Preparation Method |
KRAS G12D mutant LS513 cells were cultured in RPMI-1640 medium, supplemented with 10% fetal bovine serum (FBS), 1% penicillin-streptomycin at 37°C in an incubator with 5% CO2. Cells were seeded in a 96-well plate at a density of 2×104 cells/well for 24h. Cells were treated with different concentrations of MRTX1133 (0, 0.1, 1, 5, 10, and 100nM) for 5 days, and the cell viability was determined. |
|
Reaction Conditions |
0, 0.1, 1, 5, 10, and 100nM; 5 days |
|
Applications |
MRTX1133 treatment inhibited the cell viability of LS513 cells in a dose-dependent manner. |
| Animal experiment [2]: | |
|
Animal models |
Female wild-type C57BL/6 mice |
|
Preparation Method |
Female wild-type C57BL/6 mice (6 weeks old; 18-22g) were maintained in a controlled environment at 21±1°C and 60% relative humidity under a 12h light/dark cycle, and were given free access to food and water. A single-cell suspension of murine 6419c5 cells was prepared in DMEM and kept on ice until injection. 6419c5 cells (1×105) were injected subcutaneously into 6-week-old C57BL/6 mice. MRTX1133 was formulated in 50mM citrate buffer pH 5.0. Once formulated, MRTX1133 was protected from light and stored at 4°C for 1 week. MRTX1133 was administered at 30mg/kg (twice a day) via i.p. injection for 7 days. Subcutaneous tumor measurements began when tumors became palpable. Subcutaneous tumors were measured daily with digital calipers for short-term experiments (every 2-3 days for longer experiments). |
|
Dosage form |
30mg/kg; twice a day; 7 days; i.p. |
|
Applications |
MRTX1133 treatment significantly inhibited tumor growth in the mice with 6419c5 xenografts. |
References: [1] Feng J, Hu Z, Xia X, et al. Feedback activation of EGFR/wild-type RAS signaling axis limits KRASG12D inhibitor efficacy in KRAS G12D-mutated colorectal cancer[J]. Oncogene, 2023, 42(20): 1620-1633. [2] Kemp S B, Cheng N, Markosyan N, et al. Efficacy of a small-molecule inhibitor of KrasG12D in immunocompetent models of pancreatic cancer[J]. Cancer discovery, 2023, 13(2): 298-311. | |
| Cas No. | 2621928-55-8 | SDF | |
| Formula | C33H31F3N6O2 | M.Wt | 600.63 |
| Solubility | DMSO : 50 mg/mL | Storage | Store at -20°C |
| 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. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 1.6649 mL | 8.3246 mL | 16.6492 mL |
| 5 mM | 333 μL | 1.6649 mL | 3.3298 mL |
| 10 mM | 166.5 μL | 832.5 μL | 1.6649 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
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
- View current batch:
- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 16 reference(s) in Google Scholar.)