2. GPCR/G Protein MAPK/ERK Pathway Metabolic Enzyme/Protease Stem Cell/Wnt Apoptosis
  3. Ras Phosphatase ERK Apoptosis
  4. BBO-11818

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.

For research use only. We do not sell to patients.

BBO-11818

BBO-11818 Chemical Structure

CAS No. : 3029443-36-2

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Customer Review

Based on 1 publication(s) in Google Scholar

Other Forms of BBO-11818:

BBO-11818 Related Antibodies

Top Publications Citing Use of Products

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K-Ras H-Ras N-Ras Ras

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ERK ERK1 ERK2 ERK5 ERK8

  • Biological Activity

  • Purity & Documentation

  • References

  • Customer Review

Description

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[1][2].

IC50 & Target

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)

In Vitro

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.

BBO-11818 Related Antibodies

Cell Viability Assay[2]

Cell Line: KRAS-dependent Ba/F3 cell lines (KRASG12A, G12D, G12R, G12S, G12V, G13D, A59G, Q61H, Q61K, Q61L, WT)
Concentration: 11-point 1:3 dose titration
Incubation Time: 96 h
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.

Cell Viability Assay[2]

Cell Line: Human cancer cell lines (KRASG12D, G12V, G12C, G12A, G12R, G12S, G13D, Q61X, KRASAMP, HRASmut, NRASmut, BRAFmut)
Concentration: Nine-point 1:3 dose titration
Incubation Time: 72-hour spheroid formation, 96-hour incubation
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.
In Vivo

BBO-11818 (10-100 mg/kg; p.o.; BID; 28 d) induces potent and statistically significant tumor growth inhibition and tumor regression in KRASG12D-mutant HPAC pancreatic cancer CDX models[1].
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.

Animal Model: Immunocompromised mice[1]
Dosage: 10 mg/kg; 30 mg/kg; 100 mg/kg
Administration: p.o.; BID; 28 days
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.
Animal Model: BALB/c nude[2]
Dosage: 10 mg/kg; 30 mg/kg; 100 mg/kg
Administration: p.o.; single dose
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.
Molecular Weight

733.73

Formula

C34H33F6N7O3S
CAS No.
Appearance

Solid

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
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

Please store the product under the recommended conditions in the Certificate of Analysis.
Solvent & Solubility
In Vitro: 

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)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 1.3629 mL 6.8145 mL 13.6290 mL
5 mM 0.2726 mL 1.3629 mL 2.7258 mL
View the Complete Stock Solution Preparation Table

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  • Dilution Calculator

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In Vivo:

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.

  • Protocol 1

    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.
  • Protocol 2

    Add each solvent one by one:  10% DMSO    90% Corn Oil

    Solubility: ≥ 2.5 mg/mL (3.41 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator
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Calculation results:
Working solution concentration: mg/mL
Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
 If the continuous dosing period exceeds half a month, please choose this protocol carefully.
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.
Purity & Documentation
References

Complete Stock Solution Preparation Table

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
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
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BBO-11818 Related Classifications

Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

BBO-118183029443-36-2BBO11818BBO 11818RasPhosphataseERKApoptosisExtracellular signal regulated kinasesMAPK signalingnon-small cell lung cancerRAF1ERK phosphorylationHRASxenograft modelsKRASpancreatic cancerNRAScolorectal cancerInhibitorinhibitorinhibit

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