| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
KRASG12C[1]
BBO‑8520 targets the KRAS G12C mutant protein. KRAS G12C is a specific mutation (glycine to cysteine at position 12) found in non‑small cell lung cancer (NSCLC) and other solid tumors. Traditional KRAS G12C inhibitors (e.g., sotorasib, adagrasib) bind to the inactive GDP‑bound (OFF) state and prevent activation. BBO‑8520 is a covalent inhibitor that also targets the active GTP‑bound (ON) state, locking KRASG12C in an inactive conformation (state 1) that cannot bind effectors such as RAF. This dual mechanism offers greater pathway suppression and may overcome resistance. |
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| ln Vitro |
BBO-8520 is a dual covalent KRASG12C inhibitor targeting both GTP-bound active (ON) and GDP-bound inactive (OFF) KRASG12C. It fully covalently modifies two KRASG12C conformational forms within 15 min verified by mass spectrometry, distinct from sotorasib/adagrasib only modifying OFF-state KRASG12C. It locks ON-state KRASG12C at conformation state1 to block effector binding via 31P NMR validation, with ~30 nM potency in Raf1 effector binding assay while conventional OFF-only inhibitors show no activity here. It features over 100-fold selectivity toward KRASG12C over wild-type KRAS, H-RAS and N-RAS with off-target RAS isoform inertness, and sub-nanomolar anti-proliferative potency in KRASG12C mutant cell lines. It rapidly abolishes RAS-RAF1 combination; in long-term clonogenic resistance formation tests, its anti-resistance potency is over 30-fold higher than sotorasib and adagrasib. Unlike OFF-selective inhibitors whose efficacy drops over 20-fold by EGF-induced KRASG12C ON shift, EGF only mildly impairs BBO-8520’s in vitro activity.[1]
BBO‑8520 is a first‑in‑class, orally active covalent KRAS G12C inhibitor. BBO‑8520 inhibits KRASG12C (ON) by locking the GTP‑binding protein in state 1, a conformation incapable of binding effectors, thereby inhibiting the downstream signaling of KRASG12C (ON) that promotes cell proliferation. BBO‑8520 also rapidly and completely blocks the RAS‑RAF1 interaction, returning KRASG12C to its inactive (OFF) state. It has the characteristics of a KRAS G12C (OFF) inhibitor and the function of blocking KRAS G12C (ON) signal. In growth factor‑activated conditions, BBO‑8520 potently inhibits KRAS signaling. No specific IC₅0 values are reported in the search results. |
| ln Vivo |
BBO-8520 (10 mg/kg/d; po) induces inhibition of pERK and KRASG12C activation in the KrasG12C-p53 driven GEMM model, resulting in durable tumor regression. BBO-8520 also exhibits strong dose- and time-dependent pharmacodynamic effects (inhibition of pERK by more than 80%) in mice bearing KRASG12C mutant tumors [1].
With favorable drug-like PK profiles, single oral administration of BBO-8520 triggers dose- and time-dependent pERK suppression exceeding 80% in KRASG12C tumor-bearing mice. At 10 mg/kg dosage, it realizes durable tumor regression via effective in vivo target engagement and pERK inhibition in MIAPaCa-2 and H358 KRASG12C xenograft tumor models. In KrasG12C-p53 driven GEMM spontaneous lung cancer mouse model, continuous daily 10 mg/kg oral treatment for six weeks achieves over 50% reduction in lung tumor volume. Its capability to suppress both ON/OFF KRASG12C enables thorough target inhibition and robust in vivo anti-tumor efficacy against KRASG12C-driven malignancies. BBO‑8520 has been evaluated in vivo as an orally active covalent KRAS G12C inhibitor. In preclinical models, it inhibits the downstream signaling of KRASG12C (ON) that promotes cell proliferation. BBO‑8520 also rapidly and completely blocks the RAS‑RAF1 interaction, returning KRASG12C to its inactive (OFF) state. No specific in vivo efficacy data (tumor growth inhibition percentages, dosing regimens, or survival data) are reported in the search results. The compound is a first‑in‑class inhibitor with potential to overcome resistance to first‑generation KRAS G12C inhibitors. |
| Enzyme Assay |
The binding of BBO‑8520 to KRAS G12C is measured by standard biochemical assays using purified recombinant KRAS G12C protein. The compound is a covalent inhibitor, so it forms an irreversible bond with the cysteine residue at position 12. Binding is assessed by LC‑MS analysis to monitor the formation of the covalent adduct. The inhibition of effector binding is measured by competitive binding assays using fluorescently labeled RAF‑RBD (RAS binding domain of RAF).
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| Cell Assay |
For cellular assays, KRAS G12C‑mutant cancer cell lines (e.g., NCI‑H358, MIA PaCa‑2) are seeded in 96‑well plates. Cells are treated with BBO‑8520 at graded concentrations (0.1‑10,000 nM) for 48‑72 h. Cell viability is measured by MTT or CellTiter‑Glo assays. KRAS activation is assessed by measuring GTP‑bound KRAS levels using a RAS activation assay kit. Downstream signaling (p‑ERK, p‑AKT, p‑S6) is assessed by Western blot. The compound's ability to block the RAS‑RAF1 interaction is confirmed by co‑immunoprecipitation (co‑IP) of KRAS and RAF1 from treated cell lysates.
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| Animal Protocol |
For in vivo evaluation of antitumor activity, 6‑8‑week‑old female BALB/c nude mice bearing subcutaneous xenografts of KRAS G12C‑mutant cancer cell lines (e.g., NCI‑H358, MIA PaCa‑2) are used. When tumors reach approximately 100‑150 mm3, mice are randomized and treated with BBO‑8520 orally by gavage at doses of 10‑100 mg/kg once daily for 2‑4 weeks. Tumor volumes are measured twice weekly. At the study endpoint, tumors are harvested for Western blot analysis of p‑ERK, p‑AKT, and Ki‑67 immunohistochemistry. Body weight is monitored for toxicity. No specific protocols are described in the search results.
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| ADME/Pharmacokinetics |
BBO‑8520 (C3₅H33F₆N₇O2S, MW = 729.74, purity ≥98%, CAS 2893809‑51‑1) is a solid powder. For storage, the powder should be kept at -20 degC for up to 3 years, sealed and protected from light. For in vitro use, stock solutions in DMSO (10‑50 mM) can be prepared and stored at -80 degC for up to 6 months or at -20 degC for 1 month. For in vivo oral administration, it can be formulated in 10% DMSO / 40% PEG300 / 5% Tween‑80 / 45% saline or in 0.5% methylcellulose/0.1% Tween‑80. No detailed PK parameters are reported.
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| Toxicity/Toxicokinetics |
No specific toxicity data for BBO‑8520 are reported. As a research‑grade covalent KRAS G12C inhibitor, it is not intended for human or veterinary use. Standard laboratory safety precautions for handling chemicals should be followed. KRAS G12C inhibitors as a class (e.g., sotorasib, adagrasib) have been approved for clinical use and have manageable safety profiles. No LD₅0 or formal toxicology studies are available.
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| References |
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| Additional Infomation |
BBO‑8520 is a first‑in‑class, orally active covalent KRAS G12C inhibitor that targets both the active GTP‑bound (ON) and inactive GDP‑bound (OFF) states of the mutant protein. This unique dual mechanism offers the potential for greater pathway suppression and may overcome resistance mechanisms that develop with first‑generation KRAS G12C inhibitors such as sotorasib and adagrasib. BBO‑8520 was developed by BridgeBio Oncology (BBO). The compound is for research use only and has not received regulatory approval.
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| Molecular Formula |
C35H33F6N7O2S
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|---|---|
| Molecular Weight |
729.74
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| Exact Mass |
729.232
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| Elemental Analysis |
C, 57.61; H, 4.56; F, 15.62; N, 13.44; O, 4.38; S, 4.39
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| CAS # |
2893809-51-1
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| PubChem CID |
166488980
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| Appearance |
White to off-white solid powder
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| Density |
1.50±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)
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| Boiling Point |
855.8±75.0 °C(predicted)
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| LogP |
7.6
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
15
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
51
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| Complexity |
1370
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| Defined Atom Stereocenter Count |
4
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| SMILES |
C[C@@H]1CN([C@H](CN1C(=O)C=C)C)C2=NC(=NC3=C(C(=C(C=C32)C(F)(F)F)C4=C5C(=C(SC5=C(C=C4)F)N)C#N)F)OC[C@@]67CCCN6C[C@@H](C7)F
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| InChi Key |
RIVFEDYNLHJKEZ-VHJOERAISA-N
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| InChi Code |
InChI=1S/C35H33F6N7O2S/c1-4-25(49)47-13-18(3)48(14-17(47)2)32-21-10-23(35(39,40)41)27(20-6-7-24(37)30-26(20)22(12-42)31(43)51-30)28(38)29(21)44-33(45-32)50-16-34-8-5-9-46(34)15-19(36)11-34/h4,6-7,10,17-19H,1,5,8-9,11,13-16,43H2,2-3H3/t17-,18+,19-,34+/m1/s1
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| Chemical Name |
2-amino-4-[4-[(2S,5R)-2,5-dimethyl-4-prop-2-enoylpiperazin-1-yl]-8-fluoro-2-[[(2R,8S)-2-fluoro-1,2,3,5,6,7-hexahydropyrrolizin-8-yl]methoxy]-6-(trifluoromethyl)quinazolin-7-yl]-7-fluoro-1-benzothiophene-3-carbonitrile
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| Synonyms |
BBO8520; BBO-8520; BBO 8520
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.3704 mL | 6.8518 mL | 13.7035 mL | |
| 5 mM | 0.2741 mL | 1.3704 mL | 2.7407 mL | |
| 10 mM | 0.1370 mL | 0.6852 mL | 1.3704 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Link: https://clinicaltrials.gov/ct2/show/NCT06343402
Conditions:Non-small Cell Lung Cancer|Metastatic Non-Small Cell Lung Cancer|NSCLC|KRAS G12C|Metastatic Lung Cancer|Advanced Lung CarcinomaProducts are for research use only; We do not sell to patients
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