BBO-11818 (2.5 nM; 21 d) inhibited long-term clonogenic growth of Capan-2 PDAC (KRASG12V) cells[1].
BBO-11818 (3 nM; 15 d) inhibited long-term clonogenic growth of LS513 colorectal cancer (KRASG12D) cells[1].
BBO-11818 (30 nM; 4 h) potently and selectively inhibited SOS-mediated KRAS (wild-type and oncogenic mutant) nucleotide exchange, including the constitutively GTP-binding KRASA59G mutant, but had no activity against NRAS[2]. BBO-11818 (0.1–200 nM; 96 h) potently inhibited the viability of Ba/F3 cells driven by wild-type or oncogenic KRAS mutants (including constitutively GTP-bound KRASA59G), with reduced activity in KRASG12R and KRASQ61X mutants [2].
BBO-11818 (0–0.1 μM; 72 h & 96 h) potently and selectively inhibited 3D spheroid growth in human cancer cell lines driven by oncogenic KRAS mutations or KRAS amplification, with very low activity in non-KRAS-driven cell lines [2].

BBO-11818 (10-100 mg/kg; p.o.; BID; 28 d) induced potent and statistically significant tumor growth inhibition and tumor regression in a CDX model of HPAC pancreatic cancer carrying the KRASG12D mutation [1].
BBO-11818 (10-100 mg/kg; p.o.; BID; 28 d) induced potent, dose-dependent, and statistically significant tumor growth inhibition in a CDX model of H441 non-small cell lung cancer carrying the KRASG12V mutation [1].
BBO-11818 (100 mg/kg; p.o.; BID) induced a significant reduction in tumor cell proliferation and promoted increased apoptosis levels in a CDX model of Capan-2 pancreatic cancer with the KRASG12V mutation [1]. BBO-11818 (10-100 mg/kg; p.o.; single dose) produced dose- and time-dependent pERK and DUSP6 inhibition in KRASG12D pancreatic cancer (PDAC) xenografts, with an in vivo EC50 of 138 nmol/L for pERK inhibition and a maximum reduction of 85% in pERK levels at a single oral dose of 100 mg/kg[2].

Cell viability assay [2]
Cell lines: KRAS-dependent Ba/F3 cell lines (KRASG12A, G12D, G12R, G12S, G12V, G13D, A59G, Q61H, Q61K, Q61L, WT)
Concentration: 11 points 1:3 dose titration
Incubation time: 96 hours
Results: Effectively inhibited the viability of KRAS-dependent Ba/F3 cell lines, EC50 values ​​were as follows: 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).
Activity was reduced 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 viability assay[2]
Cell lines: Human cancer cell lines (KRASG12D, G12V, G12C, G12A, G12R, G12S, G13D, Q61X, KRASAMP, HRASmut, NRASmut, BRAFmut)
Concentration: 1:3 dose titration
Incubation time: 72 hours for spheroid formation, 96 hours for incubation
Results: Effectively inhibited the viability of 3D spheroids in KRAS mutant and KRASAMP cell lines. The following are the average 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) and KRASAMP (7.62 nmol/L) were also mentioned.
The activity was limited in KRASG12R (400 nmol/L) and KRASQ61X (3170 nmol/L) cell lines, and extremely low in HRASmut (4030 nmol/L), NRASmut (3720 nmol/L), and BRAFmut (7430 nmol/L) cell lines.

Animal model: Immunodeficient mice [1]
Dosage: 10 mg/kg; 30 mg/kg; 100 mg/kg
Routine of administration: Oral; twice daily; for 28 days
Results: At a dose of 10 mg/kg twice daily, the tumor growth inhibition rate (TGI) reached 56%, which was statistically significant.
At a dose of 30 mg/kg BID, the tumor growth inhibition rate (TGI) reached 87%, and the mean tumor regression rate (REG) reached 57%, which was statistically significant.
At a dose of 100 mg/kg BID, the tumor growth inhibition rate (TGI) reached 87%, and the mean tumor regression rate (REG) reached 57%, which was statistically significant.
At a dose of 10 mg/kg BID, the tumor growth inhibition rate (TGI) reached 14%, which was statistically significant compared with the solvent control group.
At a dose of 30 mg/kg BID, the tumor growth inhibition rate (TGI) reached 42%, which was statistically significant compared with the solvent control group.
At a dose of 100 mg/kg BID, the tumor growth inhibition rate (TGI) reached 81%, which was statistically significant compared with the solvent control group.

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Animal model: BALB/c nude mice [2]
Dose: 10 mg/kg; 30 mg/kg; 100 mg/kg
Route of administration: Oral; Single dose
Results: Compared with the control group, tumor pERK levels decreased by 27% 6 hours after administration of 10 mg/kg.
Compared with the control group, tumor pERK levels decreased by 45% 6 hours after administration of 30 mg/kg.
Compared with the control group, tumor pERK levels decreased by 85% 6 hours after administration of 100 mg/kg.
Compared to the control group, tumor DUSP6 mRNA levels decreased by 27% 6 hours after administration of 10 mg/kg.
Compared to the control group, tumor DUSP6 mRNA levels decreased by 54% 6 hours after administration of 30 mg/kg.
Compared to the control group, tumor DUSP6 mRNA levels decreased by 84% 6 hours after administration of 100 mg/kg.
At 2 hours after administration, pERK levels decreased by 67%, 85%, 81%, and 77%, respectively. Compared to the vector group, at 6, 12, and 24 hours after administration, DUSP6 levels in the 100 mg/kg group decreased by 60%, 84%, 81%, and 66%, respectively.
Compared to the carrier group, the DUSP6 levels in the 100 mg/kg dose group decreased by 60%, 84%, 81%, and 66% at 2, 6, 12, and 24 hours post-administration, respectively.
The in vivo EC50 of the pERK inhibitor was 138 nmol/L, and the EC90 was 411 nmol/L.

[1]. Discovery of BBO-11818, a Potent and Selective Noncovalent Inhibitor of (ON) and (OFF) KRAS with Activity against Multiple Oncogenic Mutants[J]. Cancer Discovery, 2026: OF1-OF20.

[2]. Discovery of BBO-11818, a Potent and Selective Noncovalent Inhibitor of (ON) and (OFF) KRAS with Activity against Multiple Oncogenic Mutants. Cancer Discov. Published online March 6, 2026.

C34H33F6N7O3S

733.73

733.227

3029443-36-2

177700565

Off-white to light yellow powder

7.4

1

16

8

51

1330

0

CCN([C@H]1CCN(C1)C(=O)OC)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

VJMZMAQRBQSNHW-AXZPFCHASA-N

InChI=1S/C34H33F6N7O3S/c1-3-47(18-7-10-45(15-18)32(48)49-2)30-20-11-22(34(38,39)40)25(19-5-6-23(36)28-24(19)21(13-41)29(42)51-28)26(37)27(20)43-31(44-30)50-16-33-8-4-9-46(33)14-17(35)12-33/h5-6,11,17-18H,3-4,7-10,12,14-16,42H2,1-2H3/t17-,18+,33+/m1/s1

methyl (3S)-3-[[7-(2-amino-3-cyano-7-fluoro-1-benzothiophen-4-yl)-8-fluoro-2-[[(2R,8S)-2-fluoro-1,2,3,5,6,7-hexahydropyrrolizin-8-yl]methoxy]-6-(trifluoromethyl)quinazolin-4-yl]-ethylamino]pyrrolidine-1-carboxylate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~136.29 mM; With ultrasound)

Solubility in Formulation 1: 2.5 mg/mL (3.41 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD powder in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (3.41 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)