KRAS G12C-IN-74
KRAS G12C-IN-74 is an orally active, selective KRASG12C inhibitor with a target IC50 of 43.18 nM. KRAS G12C-IN-74 induces G0/G1 cell cycle arrest and apoptosis in KRASG12C-mutant cancer cells. KRAS G12C-IN-74 is applicable for the research of KRASG12C-mutant pancreatic cancer, colorectal cancer and lung cancer.
For research use only. We do not sell to patients.
- CAS No.: 3085516-79-3
- Formula: C33H38FN7O2S
- Molecular Weight:615.76
-
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]
-
Biological Activity
-
Chemical Information
- Purity & Documentation
- References
-
Help & FAQs
Biological Activity
|
KRas G12C 43.18 nM (IC50) |
KRAS G12C-IN-74 (Compound 7q) (7 days) potently inhibits the proliferation of NCI-H358 3D cell spheroids, with an IC50 of 0.42 nM[1].
KRAS G12C-IN-74 (72 h) potently inhibits the proliferation of KRASG12C mutant cell lines, with IC50 values ranging from 0.42 nM (NCI-H358, 3D) to 3.331 μM (H1373), while it shows weak activity against non-G12C KRAS mutant cell lines and wild-type cell lines[1].
KRAS G12C-IN-74 (200-800 nM; 48 h) induces cell cycle arrest at the G0/G1 phase and triggers apoptosis in NCI-H358 cells[1].
KRAS G12C-IN-74 (1-8 μM; 48 h) induces dose-dependent apoptosis in NCI-H1373 cells, and when combined with ML385 (HY-100523) or RBN-2397 (HY-136174), the apoptosis rates after 48 h of incubation increase significantly to 81.28% and 82.75%, respectively[1].
Combination treatment with KRAS G12C-IN-74 (72 h) and the pan-USP inhibitor PR-619 (HY-13814) drastically reduces its IC50 against intrinsically resistant NCI-H1373 cells from the micromolar to the nanomolar range[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Cell Line:NCI-H1373 (KRASG12C mutant, intrinsically resistant) cells
-
Concentration:1 μM, 4 μM, 8 μM (alone); 8 μM + 0.2 μM ML385; 8 μM + 0.2 μM RBN-2397
-
Incubation Time:48 h
-
Result:Induced apoptosis in H1373 cells in a dose-dependent manner, with an apoptotic rate of 34% at 8 μM.
Increased the apoptotic rate to 81.28% when combined with 0.2 μM ML385, and to 82.75% when combined with 0.2 μM RBN-2397.
KRAS G12C-IN-74 (100 mg/kg; p.o.; once daily for 21 consecutive days) exhibits potent anti-tumor activity by inhibiting tumor growth in the SW837 colorectal cancer xenograft model[1].
KRAS G12C-IN-74 (30-100 mg/kg; p.o.; once daily for 9-18 consecutive days) exhibits statistically significant but modest single-agent activity in the H1373 lung cancer xenograft model, and shows synergistic anti-tumor activity when combined with ML385, RBN-2397 and PR-619[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Animal Model:NU/NU nude mice (~6 weeks old, 20-25 g)[1]
-
Dosage:3 mg/kg; 10 mg/kg; 30 mg/kg
-
Administration:p.o.; daily; 21 days
-
Result:Demonstrated a tumor growth inhibition (TGI) rate of 94.2% at 10 mg/kg.
Achieved complete tumor responses in 2 out of 5 mice at 30 mg/kg.
Maintained stable body weights across all treatment groups throughout the 21-day study.
-
Animal Model:NU/NU nude mice (~6 weeks old, 20-25 g)[1]
-
Dosage:100 mg/kg
-
Administration:p.o.; daily; 21 days
-
Result:Achieved a tumor growth inhibition (TGI) rate of 87.2%.
-
Animal Model:NU/NU nude mice (~6 weeks old, 20-25 g)[1]
-
Dosage:30 mg/kg; 100 mg/kg
-
Administration:p.o.; daily; 18 days
-
Result:Demonstrated statistically significant tumor growth inhibition at 100 mg/kg, with modest overall therapeutic efficacy compared to activity in other models.
-
Animal Model:NU/NU nude mice (~6 weeks old, 20-25 g)[1]
-
Dosage:100 mg/kg (in combination with 25 mg/kg ML385)
-
Administration:p.o.; daily; 9 days (KRAS G12C-IN-74); i.p.; daily; 9 days (ML385)
-
Result:Produced substantially enhanced antitumor efficacy when combined with 25 mg/kg ML385, with significantly greater tumor growth inhibition than either monotherapy.
-
Animal Model:NU/NU nude mice (~6 weeks old, 20-25 g)[1]
-
Dosage:30 mg/kg (in combination with 10 mg/kg RBN-2397)
-
Administration:p.o.; daily; 15 days
-
Result:Displayed marked synergistic tumor growth inhibition when combined with 10 mg/kg RBN-2397, overcoming H1373 resistance to single-agent KRAS G12C inhibition.
-
Animal Model:NU/NU nude mice (~6 weeks old, 20-25 g)[1]
-
Dosage:30 mg/kg (in combination with 5 mg/kg PR-619); 100 mg/kg (in combination with 5 mg/kg PR-619)
-
Administration:p.o.; daily; 15 days (KRAS G12C-IN-74); i.p.; every other day; 7 days (PR-619)
-
Result:Achieved a tumor growth inhibition (TGI) rate of 50.6% when 30 mg/kg was combined with 5 mg/kg PR-619.
Achieved a TGI rate of 66.3% when 100 mg/kg was combined with 5 mg/kg PR-619, with 1 out of 4 mice showing complete tumor remission.
Did not show statistically significant activity versus control as a single agent at 30 mg/kg.
Chemical Information
-
CAS No. 3085516-79-3
-
Molecular Weight 615.76
-
Formula C33H38FN7O2S
-
SMILES
O=C(N1[C@H](CN(C2=NC(OCC34N(CCC4)CCC3)=NC5=C2CCN(C5)C6=CC=CC7=C6C(C)=CS7)CC1)CC#N)C(F)=C
-
Shipping
Room temperature in continental US; may vary elsewhere.
-
Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
KRAS G12C-IN-74 Related Classifications
HY-181716 Related Classifications
Powered by Bioz