BBO-11818
Based on 1 Customer Validation
BBO-11818 is an orally active, highly selective (relative to NRAS and HRAS), non-covalent pan-KRAS inhibitor (IC50=28-120 nM). BBO-11818 specifically binds to the Switch-II/Helix 3 pocket, disrupts the KRAS:RAF1 interaction by inducing conformational changes, and blocks the MAPK signaling pathway. BBO-11818 exhibits significant anti-tumor activity, which not only inhibits cell proliferation and induces apoptosis, but also drives tumor regression in xenograft models. BBO-11818 produces synergistic effects when combined with Cetuximab (HY-P9905), anti-PD-1 antibody or PI3Kα inhibitor. BBO-11818 is used in the research of KRAS mutation-related malignancies such as pancreatic cancer, non-small cell lung cancer and colorectal cancer.
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研究用途以外に使用した場合、当社は一切の責任を負いかねます。
- 純度: 99.77%
- CAS 番号: 3029443-36-2
- 分子式: C34H33F6N7O3S
- 分子量:733.73
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保管条件: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]
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生物活性
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化学情報
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溶剤 & 溶解度
- 純度とドキュメンテーション
- 参考文献
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Help & FAQs
生物活性
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K-Ras WT 28 nM (IC50) |
KRAS(G12D) 61 nM (IC50) |
KRas G12V 47 nM (IC50) |
KRAS(G12C) 51 nM (IC50) |
KRas G12R 120 nM (IC50) |
BBO-11818 (2.5 nM; 21 d) inhibits the long-term clonogenic growth of Capan-2 PDAC (KRASG12V) cells[1].
BBO-11818 (3 nM; 15 d) inhibits the long-term clonogenic growth of LS513 colorectal cancer (KRASG12D) cells[1].
BBO-11818 (30 nM; 4 h) potently and selectively inhibits SOS-mediated nucleotide exchange of KRAS (wild-type and oncogenic mutants), including the constitutively GTP-bound KRASA59G mutant, but shows no activity against NRAS[2].
BBO-11818 (0.1-200 nM; 96 h) potently inhibits the viability of Ba/F3 cells driven by wild-type or oncogenic KRAS mutants, including the constitutively GTP-bound KRASA59G, while its activity is reduced in KRASG12R and KRASQ61X mutants[2].
BBO-11818 (0-0.1 μM; 72 h & 96 h) potently and selectively inhibits 3D spheroid growth of human cancer cell lines driven by oncogenic KRAS mutations or KRAS amplification, while exhibiting extremely low activity in non-KRAS-driven cell lines[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:KRAS-dependent Ba/F3 cell lines (KRASG12A, G12D, G12R, G12S, G12V, G13D, A59G, Q61H, Q61K, Q61L, WT)
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Concentration:11-point 1:3 dose titration
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Incubation Time:96 h
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Result:Potently inhibited viability in KRAS-dependent Ba/F3 cell lines with the following EC50 values: KRASG12A (0.824 nmol/L), KRASG12D (1.33 nmol/L), KRASG12S (0.505 nmol/L), KRASG12V (5.84 nmol/L), KRASG13D (1.13 nmol/L), KRASA59G (3.28 nmol/L), KRAS WT (8.99 nmol/L).
Showed reduced activity in KRASG12R (22.9 nmol/L), KRASQ61H (53.3 nmol/L), KRASQ61K (48.4 nmol/L), and KRASQ61L (136 nmol/L) cell lines.
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Cell Line:Human cancer cell lines (KRASG12D, G12V, G12C, G12A, G12R, G12S, G13D, Q61X, KRASAMP, HRASmut, NRASmut, BRAFmut)
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Concentration:Nine-point 1:3 dose titration
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Incubation Time:72-hour spheroid formation, 96-hour incubation
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Result:Potently inhibited 3D spheroid viability in KRAS-mutant and KRASAMP cell lines with the following mean EC50 values: KRASG12D (2.21 nmol/L), KRASG12V (31.2 nmol/L), KRASG12C (2.26 nmol/L), KRASG12A (5.32 nmol/L), KRASG12S (3.09 nmol/L), KRASG13D (71.7 nmol/L), KRASAMP (7.62 nmol/L).
Showed limited activity in KRASG12R (400 nmol/L) and KRASQ61X (3170 nmol/L) cell lines, and minimal activity in HRASmut (4030 nmol/L), NRASmut (3720 nmol/L), and BRAFmut (7430 nmol/L) cell lines.
BBO-11818 (10-100 mg/kg; p.o.; BID; 28 d) induces potent, dose-dependent, and statistically significant tumor growth inhibition in the KRASG12V-mutant H441 non-small cell lung cancer CDX model[1].
BBO-11818 (100 mg/kg; p.o.; BID) induces a statistically significant reduction in tumor cell proliferation and promotes an increase in apoptosis levels in the KRASG12V-mutant Capan-2 pancreatic cancer CDX model[1].
BBO-11818 (10-100 mg/kg; p.o.; single administration) exerts dose- and time-dependent inhibition of pERK and DUSP6 in KRASG12D pancreatic ductal adenocarcinoma (PDAC) xenografts, with an in vivo EC50 of 138 nmol/L for pERK inhibition; pERK levels are reduced by up to 85% following a single oral dose of 100 mg/kg[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Immunocompromised mice[1]
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Dosage:10 mg/kg; 30 mg/kg; 100 mg/kg
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Administration:p.o.; BID; 28 days
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Result:Achieved 56% tumor growth inhibition (TGI) at 10 mg/kg BID, with statistical significance.
Achieved 87% TGI and 57% mean tumor regression (REG) at 30 mg/kg BID, with statistical significance.
Achieved 87% TGI and 57% REG at 100 mg/kg BID, with statistical significance.\n
Achieved 14% tumor growth inhibition (TGI) at 10 mg/kg BID, with statistical significance relative to vehicle.
Achieved 42% TGI at 30 mg/kg BID, with statistical significance relative to vehicle.
Achieved 81% TGI at 100 mg/kg BID, with statistical significance relative to vehicle.
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Animal Model:BALB/c nude[2]
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Dosage:10 mg/kg; 30 mg/kg; 100 mg/kg
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Administration:p.o.; single dose
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Result:Reduced tumor pERK levels by 27% at 6 hours post 10 mg/kg dose relative to vehicle.
Reduced tumor pERK levels by 45% at 6 hours post 30 mg/kg dose relative to vehicle.
Reduced tumor pERK levels by 85% at 6 hours post 100 mg/kg dose relative to vehicle.
Reduced tumor DUSP6 mRNA levels by 27% at 6 hours post 10 mg/kg dose relative to vehicle.
Reduced tumor DUSP6 mRNA levels by 54% at 6 hours post 30 mg/kg dose relative to vehicle.
Reduced tumor DUSP6 mRNA levels by 84% at 6 hours post 100 mg/kg dose relative to vehicle.
Reduced pERK levels by 67%, 85%, 81%, and 77% at 2, 6, 12, and 24 hours post 100 mg/kg dose relative to vehicle, respectively.
Reduced DUSP6 levels by 60%, 84%, 81%, and 66% at 2, 6, 12, and 24 hours post 100 mg/kg dose relative to vehicle, respectively.
Achieved an in vivo EC50 of 138 nmol/L and EC90 of 411 nmol/L for pERK inhibition.
化学情報
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CAS 番号 3029443-36-2
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性状 Solid
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分子量 733.73
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分子式 C34H33F6N7O3S
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Color Off-white to light yellow
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SMILES
CCN([C@H]1CCN(C1)C(OC)=O)C2=NC(OC[C@@]34CCCN3C[C@@H](C4)F)=NC5=C([C@]([C@]6=CC=C(C7=C6C(C#N)=C(S7)N)F)=C(C=C25)C(F)(F)F)F
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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
溶剤 & 溶解度
DMSO : 100 mg/mL (136.29 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.
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: 2.5 mg/mL (3.41 mM); Suspended solution; Need ultrasonic
This protocol yields a suspended solution of 2.5 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
純度とドキュメンテーション
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データシート (287 KB)
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SDS (252 KB)
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- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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取扱説明書 (2659 KB)
参考文献
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 |
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| DMSO | 1 mM | 1.3629 mL | 6.8145 mL | 13.6290 mL | 34.0725 mL |
| 5 mM | 0.2726 mL | 1.3629 mL | 2.7258 mL | 6.8145 mL | |
| 10 mM | 0.1363 mL | 0.6814 mL | 1.3629 mL | 3.4072 mL | |
| 15 mM | 0.0909 mL | 0.4543 mL | 0.9086 mL | 2.2715 mL | |
| 20 mM | 0.0681 mL | 0.3407 mL | 0.6814 mL | 1.7036 mL | |
| 25 mM | 0.0545 mL | 0.2726 mL | 0.5452 mL | 1.3629 mL | |
| 30 mM | 0.0454 mL | 0.2271 mL | 0.4543 mL | 1.1357 mL | |
| 40 mM | 0.0341 mL | 0.1704 mL | 0.3407 mL | 0.8518 mL | |
| 50 mM | 0.0273 mL | 0.1363 mL | 0.2726 mL | 0.6814 mL | |
| 60 mM | 0.0227 mL | 0.1136 mL | 0.2271 mL | 0.5679 mL | |
| 80 mM | 0.0170 mL | 0.0852 mL | 0.1704 mL | 0.4259 mL | |
| 100 mM | 0.0136 mL | 0.0681 mL | 0.1363 mL | 0.3407 mL |
BBO-11818 関連分類
HY-181420A 関連分類
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