KRAS-IN-61
KRAS-IN-61 is an orally effective pan-KRAS inhibitor that potently inhibits SOS1-mediated KRAS nucleotide exchange (IC50 <10 nM for KRAS G12D/G12V/G12C/WT). KRAS-IN-61 inhibits pERK signaling and cell proliferation in KRAS-mutant tumor cells. KRAS-IN-61 can inhibit tumor growth in vivo. KRAS-IN-61 can be used in studies of KRAS mutation-related cancers, such as colorectal cancer.
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- 화학식: C34H33F7N10O3
- 분자량:762.68
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보관:
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
- Protocol
- 순도&문서
- References
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Help & FAQs
Biological Activity
제품 설명
IC50 & Target
[1]|
KRas G12D <10 nM (IC50) |
KRas G12V <10 nM (IC50) |
KRAS(G12C) <10 nM (IC50) |
K-Ras WT <10 nM (IC50) |
In Vitro
In the active KRAS/CRAF RBD binding assay, KRAS-IN-61 shows IC50 values of 10-100 nM for KRAS G12D, 100-1000 nM for G12V, and >1000 nM for G12C[1].
In the SPR assay, KRAS-IN-61 displays an IC50 of <10 nM for binding to KRAS G12D-GDP[1].
KRAS-IN-61 exhibits IC50 values of <10 nM against KRAS-mutant GP2D (G12D), SW620 (G12V), NCI-H358 (G12C), and KE39 (G12D) cells in the pERK HTRF assay (3 h), with an IC90 of 0.90 nM in GP2D cells, while showing an IC50 of >1000 nM against wild-type KRAS A375 cells[1].
KRAS-IN-61 shows IC50 values of <10 nM against multiple KRAS-mutant cell lines in the 3-day assay[1].
KRAS-IN-61 displays IC90 values of 20.46, 14.72, 1.798, and 62.17 nM for GP2D, KE39, NCI-H358, and SW620 cells, respectively, in the 3D cell viability assay[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Female BALB/c nude mice (6-8 weeks old) received a subcutaneous injection into the right flank with 1×107 GP2D tumor cells in 100 μL DMEM:Matrigel (1:1 ratio). Mice were randomized when tumors reached an average volume of ~150 mm3[1]
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Dosage:5 mg/kg, 10 mg/kg, 30 mg/kg
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Administration:Oral gavage (p.o.); twice a day (BID); 2 weeks
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Result:Dose-dependently inhibited tumor growth over the 2-week treatment period.
Plasma concentrations of this compound exceeded its IC50 and IC90 for extended periods of time after oral administration.
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Animal Model:Female BALB/c nude mice (6-8 weeks old) received a subcutaneous injection into the right flank with 1×107 GP2D tumor cells in 100 μL DMEM:Matrigel (1:1 ratio). Mice were randomized when tumors reached an average volume of ~300 mm3[1]
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Dosage:3 mg/kg, 10 mg/kg, 30 mg/kg, 60 mg/kg
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Administration:Oral gavage (p.o.); single dose
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Result:Tumor samples were collected at 4 h, 8 h, and 24 h post-administration for pERK immunohistochemical analysis.
Sustained inhibition of ERK phosphorylation (p-ERK) was observed at 4-24 h after a single oral dose.
Plasma concentrations correlated with pERK inhibition in tumor tissue.
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Animal Model:BALB/c nude mice were inoculated subcutaneously into the right flank with 5×106 or 1×107 GP2d colorectal adenocarcinoma (KRAS G12D mutant) cells. Mice were randomized when mean tumor volume reached 300-400 mm3 (n=9 or 12/group)[1]
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Dosage:3 mg/kg, 10 mg/kg, 30 mg/kg, 60 mg/kg
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Administration:Oral gavage (p.o.); single dose
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Result:Inhibited DUSP6 mRNA expression in tumor tissue in a dose- and time-dependent manner.
- BrdU Incorporation Assay
- Somatic Cell Culture
- CFSE Dye Dilution Proliferation Assay
- Dye-dilution cell tracking and proliferation staining
- Patient-Derived Orthotopic Xenograft (PDOX)
- CCK-8/WST-8 Cell Proliferation Assay
- Protocol for Cell Cycle
- Cell Counting-Based Growth Curve Assay
- Colony Formation (Clonogenic) Assay
- Cell Viability Determination by MTT Colorimetric Assay
- EdU Incorporation Assay (Click Chemistry-Based DNA Synthesis Measurement)
- Ki-67 Immunostaining Proliferation Assay
- PCNA Immunodetection Proliferation Assay
- Protocol for Cell Counting and Cell Density Analysis
- Patient-Derived Xenograft (PDX)
- MTT Cell Proliferation Assay
- Subcutaneous Cell-Line-Derived Xenograft
- Orthotopic Cell-Line Xenograft
- Genotoxicity/Mutagenicity Study
Chemical Information
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분자량 762.68
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화학식 C34H33F7N10O3
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SMILES
FC(F)(F)C(C(C)=NC1=C2C=NN1)=C2C3=C(F)C4=C(C(OC[C@H](C)N5[C@H](C)C6=C(N)N=CC(OC(F)F)=C6)=N3)C5=NC(OC[C@@]78N(CCC8)C[C@H](F)C7)=N4
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Please store the product under the recommended conditions in the Certificate of Analysis.
순도&문서
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
KRAS-IN-61 Related Classifications
HY-187519 Related Classifications
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Keywords
- KRAS-IN-61
- Ras
- pan-KRAS inhibitor
- SOS1 inhibitor
- KRAS G12D inhibitor
- KRAS G12V inhibitor
- KRAS G12C inhibitor
- pERK inhibition
- RAS/MAPK pathway
- antiproliferative
- orally bioavailable
- GP2D
- SW620
- NCI-H358
- KE39
- A375
- KRAS-mutant cancer
- colorectal cancer (CRC)
- pancreatic cancer
- non-small cell lung cancer (NSCLC)
- multiple myeloma
- GP2D KRAS G12D CRC xenograft model
- BALB/c nude mice
- TR-FRET
- HTRF
- SPR
- CellTiter-Glo
- 3D cell culture
- in vivo antitumor efficacy
- Inhibitor
- inhibitor
- inhibit