BB-1701
Based on 1 Customer Validation
BB-1701 is an anti-HER2 antibody-drug conjugate (ADC). BB-1701 consists of a humanized anti-HER2 antibody (Trastuzumab) (HY-P9907), a linker (Mal-PEG2-VCP), and a microtubule inhibitor (Eribulin) (HY-13442), with the drug-linker conjugate of the ADC being Mal-PEG2-VCP-Eribulin (HY-128870). BB-1701 exhibits potent cytotoxicity against various cancer cells, shows a remarkable bystander effect, and induces immunogenic cell death (upregulated cell surface expression of calreticulin, release of ATP/HMGB1, macrophage infiltration) and apoptosis. BB-1701 potently inhibits tumor growth in T-DM1/T-DXd-resistant tumor models. BB-1701 can be used in studies related to breast cancer, gastric cancer, non-small cell lung cancer, and heterogeneous mixed tumors.
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Activité biologique
Description
IC50 & Target
[1]|
HER2 |
Cellular Effect
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Cell Line
|
Type | Value | Description | References |
|---|---|---|---|---|
| NCI-N87 | IC50 |
0.11 nM
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Cytotoxicity against human HER2-high NCI-N87 cancer cells assessed as reduction in cell viability incubated for 5 days by CCK-8 assay.
Cytotoxicity against human HER2-high NCI-N87 cancer cells assessed as reduction in cell viability incubated for 5 days by CCK-8 assay.
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39036069 |
| A549 | IC50 |
24.08 nM
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Cytotoxicity against human HER2-low A549 cancer cells assessed as reduction in cell viability incubated for 5 days by CCK-8 assay.
Cytotoxicity against human HER2-low A549 cancer cells assessed as reduction in cell viability incubated for 5 days by CCK-8 assay.
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39036069 |
| NCI-H1975 | IC50 |
8.67 nM
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Cytotoxicity against human HER2-low NCI-H1975 cancer cells assessed as reduction in cell viability incubated for 5 days by CCK-8 assay.
Cytotoxicity against human HER2-low NCI-H1975 cancer cells assessed as reduction in cell viability incubated for 5 days by CCK-8 assay.
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39036069 |
| NUGC-3 | IC50 |
16.77 nM
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Cytotoxicity against human HER2-low NUGC-3 cancer cells assessed as reduction in cell viability incubated for 5 days by CCK-8 assay.
Cytotoxicity against human HER2-low NUGC-3 cancer cells assessed as reduction in cell viability incubated for 5 days by CCK-8 assay.
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39036069 |
| U-87MG ATCC | IC50 |
> 10 nM
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Cytotoxicity against human HER2-null U87MG cancer cells assessed as reduction in cell viability incubated for 5 days by CCK-8 assay.
Cytotoxicity against human HER2-null U87MG cancer cells assessed as reduction in cell viability incubated for 5 days by CCK-8 assay.
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39036069 |
| BT-474 | IC50 |
0.352 nM
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Cytotoxicity against human BT-474 cancer cells assessed as reduction in cell viability incubated for 5 days by CCK-8 assay, measured alongside immunogenic cell death biomarker assay.
Cytotoxicity against human BT-474 cancer cells assessed as reduction in cell viability incubated for 5 days by CCK-8 assay, measured alongside immunogenic cell death biomarker assay.
|
39036069 |
In Vitro
BB-1701 exhibits an average drug-to-antibody ratio (DAR) of 4 as characterized by HIC[1].
BB-1701 (50 μg/mL; 200 s association, 300 s dissociation) binds to recombinant human HER2, with kinetic characteristics comparable to those of the naked anti-HER2 antibody[1].
BB-1701 (100 μg/mL; 0-504 h) exhibits favorable plasma stability in cynomolgus monkey plasma. After 21 days of incubation, more than 70% of intact ADC and over 90% of conjugated eribulin remain[1].
BB-1701 (~1 mg/mL; 5 min treatment at room temperature, followed by 2 h of time-lapse imaging) shows preserved endocytosis and early subcellular trafficking processes in T-DXd-resistant N87 AR gastric cancer cells, consistent with the uptake pattern observed in parental N87 cells[2].
BB-1701 (0.01-10 μg/mL; 1 h) binds to HER2 on BT-474, NCI-N87 and JIMT-1 cells with an efficiency comparable to that of the naked anti-HER2 antibody[1].
BB-1701 (10 μg/mL; 1 h ice incubation, up to 4 h 37°C incubation) is internalized by BT-474 and NCI-H1975 cells, with an internalization efficiency comparable to that of the naked anti-HER2 antibody[1].
BB-1701 (for 5 days) potently inhibits the viability of HER2-high-expressing NCI-N87 cells (IC50 = 0.11 nM), as well as HER2-low-expressing A549 cells (IC50 = 24.08 nM), NCI-H1975 cells (IC50 = 8.67 nM), NUGC-3 cells (IC50 = 16.77 nM) and U87MG cells (IC50 > 10 nM)[1].
BB-1701 (for 5 days) exerts a bystander effect, and potently inhibits the viability of HER2-negative U87MG cells when co-cultured with HER2-overexpressing NCI-N87 cells (IC50 = 0.28 nM)[1].
BB-1701 (for 5 days) induces immunogenic cell death in BT-474 cells, with an EC50 of 0.6054 nM for surface expression of calreticulin and a cytotoxic IC50 of 0.352 nM[1].
BB-1701 (0.167 nM; 24-120 h) induces transient ATP secretion in BT-474 cells, a hallmark feature of immunogenic cell death[1].
BB-1701 (0.001-10 μg/mL; 72 h) potently reduces the viability of T-DXd-resistant N87 AR gastric cancer cells in vitro, with an IC50 of 0.11 μg/mL, while the parental N87 cells also exhibit sensitivity to this agent[2].
BB-1701 (10 μg/mL; 48 h) significantly induces apoptosis in T-DXd-resistant N87 AR gastric cancer cells, as evidenced by increased levels of cleaved PARP and cleaved caspase-3[2].
BB-1701 (10 μg/mL; 24 h) significantly enhances the activity of caspase-3/7, an apoptosis marker, in T-DXd-resistant N87 AR gastric cancer cells[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:HER2-amplified T-DXd-resistant gastric cancer N87 AR cells, parental N87 cells
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Concentration:10 μg/mL
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Incubation Time:48 h
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Result:Strongly upregulated cleaved PARP and cleaved caspase-3 in N87 AR cells.
Induced cleaved PARP in parental N87 cells.
In Vivo
BB-1701 (5 mg/kg; intravenous injection; single administration) significantly inhibits tumor growth and exhibits good tolerability in NCI-N87 and NUGC-3 gastric cancer xenograft models[1].
BB-1701 (5 mg/kg; intravenous injection; single administration) potently and persistently inhibits tumor growth and prolongs survival in the NCI-H1975 non-small cell lung cancer xenograft model[1].
BB-1701 (3 mg/kg; intravenous injection; single administration) exhibits a potent in vivo bystander effect in the N87/U87-RFP mixed tumor model, and inhibits the growth of HER2-high-expressing NCI-N87 cells and HER2-negative U87-mCherry cells in mixed xenografts[1].
In cynomolgus monkeys, the HNSTD of BB-1701 (2-8 mg/kg; intravenous injection; once every 3 weeks; 4 doses total) is 4 mg/kg, and doses at or below 4 mg/kg are well tolerated; reversible hematological, immune organ and bone marrow toxicities occur at high doses, with no ILD, CNS, cardiovascular or respiratory system toxicities[1].
BB-1701 (5 mg/kg; intravenous injection) potently inhibits tumor growth and induces apoptosis of T-DXd-resistant N87 AR gastric cancer xenografts in SHO mice[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:nude mice (female, 6-8 weeks old)[1]
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Dosage:5 mg/kg
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Administration:i.v.; single dose
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Result:Induced deep and lasting tumor suppression.
Was well tolerated with no adverse effects on general condition or body weight.\nInduced complete tumor regression in all 10 treated mice (10/10 CR).
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Animal Model:nude mice (female, 6-8 weeks old)[1]
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Dosage:5 mg/kg
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Administration:i.v.; single dose
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Result:Induced significant tumor growth inhibition.
Was well tolerated with no adverse effects on general condition or body weight.\nInduced significant tumor growth inhibition.
Was well tolerated with no adverse effects on general condition or body weight.
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Animal Model:nude mice (female, 6-8 weeks old)[1]
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Dosage:5 mg/kg
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Administration:i.v.; single dose
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Result:Induced deep and lasting tumor suppression with tumor growth inhibition >95% on Day 31 and tumor regression in 2 of 5 treated mice (2/5 CR).
Significantly extended mouse survival time compared to controls.
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Animal Model:nude mice (female, 6-8 weeks old)[1]
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Dosage:3 mg/kg
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Administration:i.v.; single dose
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Result:Caused significant overall tumor growth suppression.
Mean fluorescence intensity (indicating HER2-null U87-mCherry cell growth) remained unchanged throughout the study period.
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Animal Model:Cynomolgus monkeys (male and female)[1]
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Dosage:2 mg/kg; 4 mg/kg; 8 mg/kg
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Administration:i.v.; once every 3 weeks; 4 doses
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Result:At 8 mg/kg, caused hematological toxicity (reduced WBC, neutrophils, lymphocytes, reticulocytes), immune organ toxicity (lymphoid depletion in thymus, spleen, lymph nodes, Peyer’s patches), and bone marrow toxicity (reduced cell proliferation, myeloid cell counts, altered M:E ratio); one female monkey was euthanized due to systemic bacterial infection, and one male monkey died unexpectedly.
At 4 mg/kg, caused similar but less severe changes not considered toxicologically important.
At 2 mg/kg, caused minimal and non-significant changes.
Showed no test article-related effects on the central nervous, cardiovascular, or respiratory systems at any dose.
Determined the highest nonseverely toxic dose (HNSTD) to be 4 mg/kg.
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Animal Model:SHO mice (male, 5-week-old)[2]
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Dosage:5 mg/kg
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Administration:i.v.
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Result:Significantly inhibited tumor growth compared to T-DXd treatment.
Showed higher expression of cleaved PARP and cleaved caspase-3, indicating enhanced apoptosis.
Caused no significant loss in body weight.
Essai clinique
| NCT Number | Sponsor | Condition | Start Date |
Phase
|
|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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Appearance Liquid
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Color Colorless to light yellow
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SMILES
[BB-1701]
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Livraison
Shipping with dry ice.
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Stockage
-80°C, protect from light
Pureté et documentation
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Fiche technique (286 KB)
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SDS (251 KB)
- English - EN (251 KB)
- Français - FR (251 KB)
- Deutsch - DE (251 KB)
- Norwegian - NO (251 KB)
- Español - ES (251 KB)
- Swedish - SV (251 KB)
- Italian - IT (251 KB)
- Korean - KR (251 KB)
- Portuguese - PT (251 KB)
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Instruction de manipulation (2659 KB)
Références
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
BB-1701 Related Classifications
HY-177414 Related Classifications
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