JSKN003
JSKN003 is a bispecific antibody-drug conjugate (BsADC) targeting HER2. JSKN003, constructed based on the bispecific antibody KN026 (HY-P99437), uses a proprietary Fc glycosylation site-specific conjugation technology to precisely link with DXd (HY-13631D), a topoisomerase I inhibitor. JSKN003 binds to FcγRIIIa on immune effector cells (Kd = 150 nM), thereby inducing antibody-dependent cell-mediated cytotoxicity. JSKN003 induces tumor cell apoptosis via DNA damage triggered by topoisomerase I inhibition. JSKN003 exhibits a bystander killing effect and can be used for the research of HER2-positive tumors.
Nur für Forschungszwecke. Wir verkaufen nicht an Patienten.
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Speicherung:
Please store the product under the recommended conditions in the Certificate of Analysis.
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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Biologische Aktivität
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Chemical Information
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Biologische Aktivität
JSKN003 (200 nM; 24 h) is efficiently internalized by NCI-N87 cells, and its activity is comparable to that of the parental antibody KN026[1].
JSKN003 (96 h) potently inhibits the growth of BT474 and NCI-N87 cells with high HER2 expression, with IC50 values of 0.1720 μg/mL and 0.1387 μg/mL, respectively, while shows extremely low activity against BxPC-3 cells with low HER2 expression[1].
JSKN003 (4 h) retains potent antibody-dependent cell-mediated cytotoxicity (ADCC) activity against NCI-N87 cells, with a maximum cytotoxicity of 45% at a concentration of 1 μg/mL and an EC50 of 70 ng/mL[1].
JSKN003 (0.1-10 μg/mL; 72 h) induces concentration-dependent DNA damage and apoptosis in NCI-N87 cells, which is verified by increased phosphorylation level of histone H2A.X and expanded apoptotic cell population[1].
JSKN003 (2 μg/mL; 96 h) exerts potent bystander killing activity and eliminates HER2-negative MDA-MB-231 and MDA-MB-468 cells co-cultured with HER2-positive NCI-N87 cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:NCI-N87 cells
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Concentration:0.1, 1 and 10 μg/mL
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Incubation Time:72 hours
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Result:Induced a concentration-dependent increase in histone H2A.X phosphorylation and apoptotic cell population with escalating doses, indicating induction of DNA damage and apoptosis via topoisomerase I inhibition.
JSKN003 (10 mg/kg; i.p.) demonstrates notable antitumor activity in HER2-low BxPC-3 CDX models, achieving 60% TGI at 10 mg/kg[1].
JSKN003 (2-10 mg/kg; i.v.; once per week; 2 doses) exhibits dose-dependent, potent antitumor efficacy in HER2-high gastric cancer PDX models[1].
JSKN003 (10 mg/kg; i.v.; once per week; 2 doses) demonstrates robust antitumor activity in HER2-low gastric cancer PDX models at 10 mg/kg[1].
JSKN003 (20 mg/kg; i.v.; single dose) exhibits favorable hematological safety in healthy mice at a 20 mg/kg single intravenous dose, with minimal blood cell population disturbances[1].
JSKN003 (10-80 mg/kg; i.v.; once every 3 weeks; 3 doses) has a favorable safety profile in cynomolgus monkeys up to 30 mg/kg (the HNSTD), with mild, reversible toxicities, while 80 mg/kg causes more severe, though reversible, organ toxicities[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NPI (female, specific pathogen-free)[1]
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Dosage:2 mg/kg; 10 mg/kg
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Administration:i.v.; once per week; 2 doses
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Result:Showed dose-dependent tumor regression.
Led to significant tumor shrinkage at 2 mg/kg.
Induced complete tumor regression with no tumor regrowth observed through day 40 at 10 mg/kg.
Caused no adverse effects on body weight.
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Animal Model:NOD/SCID (female)[1]
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Dosage:10 mg/kg
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Administration:i.v.; once per week; 2 doses
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Result:Inhibited tumor growth, with final tumor volume reduced to near baseline through day 30, while control tumors grew to ~750 mm3.
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Animal Model:6 to 8-week-old female[1]
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Dosage:20 mg/kg
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Administration:i.v.; single dose
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Result:Caused fewer disturbances in blood cell populations (granulocyte, lymphocyte, and monocyte percentages) compared to DS-8201a, with no significant differences relative to PBS controls.
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Animal Model:Cynomolgus monkey (5 males and 5 females per main group; 2 males and 2 females per recovery group)[1]
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Dosage:10 mg/kg; 30 mg/kg; 80 mg/kg
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Administration:i.v.; once every 3 weeks; 3 doses
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Result:Caused no mortality or life-threatening toxicities at any dose.
Caused minimal thymus cellularity decrease at 10 mg/kg, with 0/5 animals developing ADA pre-third dose and 1/2 developing ADA post-recovery.
Caused minimal to mild thymus and thyroid toxicity at 30 mg/kg, with 1/5 animals developing ADA pre-third dose and 0/2 developing ADA post-recovery; this dose was determined to be the highest non-severely toxic dose (HNSTD).
Caused reduced body weight (5-15% decrease days 1-14, later recovered), decreased food consumption, mild erythema, lung/bronchial inflammation and edema, and thymus/thyroid toxicity at 80 mg/kg, with 0/5 animals developing ADA pre-third dose and 0/2 developing ADA post-recovery.
Chemical Information
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SMILES
[JSKN003]
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Versand
Room temperature in continental US; may vary elsewhere.
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Speicherung
Please store the product under the recommended conditions in the Certificate of Analysis.
Reinheit & Dokumentation
Verweise
Calculators
Konzentration (Stammlösung) × Volumen (Stammlösung) = Konzentration (Ziellösung) × Volumen (Ziellösung)
JSKN003 Related Classifications
HY-185815 Related Classifications
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- JSKN003
- JSKN 003
- JSKN-003
- Antibody-Drug Conjugates (ADCs)
- EGFR
- Topoisomerase
- Apoptosis
- DNA/RNA Synthesis
- NCI-N87 cells
- MDA-MB-231 cells
- BxPC-3 cells
- FcγRIIIa
- topoisomerase I
- antibody-dependent cell-mediated cytotoxicity
- MDA-MB-468 cells
- HER2
- BT474 cells
- patient-derived xenograft tumor models
- Inhibitor
- inhibitor
- inhibit