KRAS-IN-62
KRAS-IN-62 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-62 inhibits pERK signaling and cell proliferation in KRAS-mutant tumor cells (pERK IC90 = 0.51 nM in GP2D cells). KRAS-IN-62 inhibits tumor growth in vivo, with plasma concentrations exceeding IC50 for ~20 h after oral administration in beagle dogs. KRAS-IN-62 can be used in studies of KRAS mutation-related cancers, such as colorectal cancer.
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- CAS No.: 3137385-11-3
- 화학식: C35H34F7N9O3
- 분자량:761.69
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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
- 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
KRAS-IN-62 (Compound 106) exhibits IC50 values of < 10 nM against KRAS G12D, G12V, G12C, and wild-type KRAS in the KRAS G12D SOS1-mediated nucleotide exchange TR-FRET assay[1].
In the active KRAS/CRAF RBD binding assay, Compound 106 shows an IC50 of 10-100 nM for KRAS G12D, and 100-1000 nM for G12V and G12C[1].
KRAS-IN-62 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 0.51 nM in GP2D cells, while showing an IC50 of > 1000 nM against wild-type KRAS A375 cells[1].
KRAS-IN-62 shows IC50 values of < 10 nM against multiple KRAS-mutant cell lines in the 3-day proliferation assay[1].
KRAS-IN-62 displays IC90 values of 1.6, 4.2, 1.7, and 10.8 nM for SW620, GP2D, KE39, and NCI-H358 cells, respectively, in the 2D cell viability assay[1].
KRAS-IN-62 displays IC90 values of 6.52, 5.22, 1.18, and 17.88 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 ~300 mm3[1]
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Dosage:3 mg/kg, 10 mg/kg, 30 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: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:3 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: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.
Chemical Information
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CAS No. 3137385-11-3
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분자량 761.69
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화학식 C35H34F7N9O3
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SMILES
FC(F)(F)C(C(C)=CC1=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-62 Related Classifications
HY-187520 Related Classifications
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Keywords
- KRAS-IN-62
- 3137385-11-3
- Ras
- SOS1
- 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