YK012
YK012 is an anti-CD19 and CD3 T cell engager with a Kd of 1.96 μM for hCD3 ε/δ and a Kd of approximately 0.5 nM for hCD19. YK012 binds CD3/TCR and activates cells only upon crosslinking by CD19-positive target cells. YK012 induces cytokine release (IL-2, TNF-α, IFN-γ, IL-6) as well as granzyme B/perforin release. YK012 alleviates pathological symptoms in a collagen-induced arthritis model. YK012 exhibits extremely low antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) activity, and does not mediate killing of CD19-negative cells. YK012 can be used for research on rheumatoid arthritis.
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
Beschreibung
Species Reactivity
Human
IC50 & Target
[1]|
IL-2 |
IL-6 |
In Vitro
YK012 binds recombinant hCD3 ε/δ with low intrinsic affinity (KD = 1.96 μM) in cell-free BIAcore assays and binds hCD19 with high affinity (approximately 0.5 nM)[1].
YK012 (30 min) binds membrane CD19 on Raji-lp cells with an apparent KD = 1.3 nM and binds B cells with an EC50 = 20.28 ng/mL, whereas membrane CD3 on Jurkat T cells has an apparent KD = 124 nM[1].
YK012 (1 µg/mL; 72 h) increased CD25+CD8+ T cells from 0.3% to 10.9% only when PBMC-derived T cells were co-cultured with CD19+ Raji cells[1].
YK012 (starting at 8 nM, 4-fold dilution; 2-24 hours) mediated time-dependent T cell cytotoxicity against CD19+ Raji-luc and NALM6-luc, with nearly complete killing at >10 pM after 24 hours[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
YK012 (0.1-0.5 mg/kg; i.v. via tail vein injection; twice a week for a total of 7 doses; D0, D3, D7, D10, D14, D17, D21) depletes peripheral blood CD79b+ B cells in huHSC-NCG-M mice, with 0.1 mg/kg showing greater depletion than 0.5 mg/kg[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:hCD3EDG/hCD19 transgenic on C57BL/6 background (male; 8 weeks old)[1]
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Dosage:0.125 mg/kg (Group C); 0.25 mg/kg (Group D); 0.5 mg/kg (Group E)
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Administration:Day 27 to Day 73; total 15 administrations; frequency adjusted
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Result:Joint scoring showed a downward trend in joint scores of YK012 dose groups compared with the model group.
Protein level detection did not reveal differences in CRP, RF, ACPA, and SAA levels among groups.
Joint pathological staining scores showed a downward trend.
Flow cytometry demonstrated changes (fluctuations) in absolute counts of peripheral blood B cells (CD20+/B220+) and T cells (TCRβ+) and their proportions, beginning on Day 33 (6 days after first administration) and partially or fully recovering in later stages of the experiment.
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Animal Model:HuHSC-NCG-M[1]
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Dosage:G1 0.1 mg/kg; G2 0.5 mg/kg
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Administration:i.v. via tail vein injection; twice a week for a total of 7 doses on D0, D3, D7, D10, D14, D17, D21
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Result:Before grouping, the average level of hCD45×hCD3 in mice was 3.31%.
After YK012 administration via tail vein injection twice a week for a total of 7 doses, there was a reduction in the number of B cells (CD79b+) in peripheral blood.
The B cell depletion effect of G1 (0.1 mg/kg) was superior to that of G2 (0.5 mg/kg).
All YK012 groups showed depletion of B cell (CD79b+) proportion and number on D1, D7, D11, D14, and D21 compared to D-5, with the degree of decrease deepening with time and number of doses.
Group G1: B cell proportion on D7 decreased; B cell proportion on D11, D14, and D21 decreased more pronouncedly.
Group G2: B cell proportion and number on D1 and B cell number on D7 decreased; B cell proportion on D7 and proportion and number on D11, D14, and D21 decreased more pronouncedly.
Compared to Group G2, Group G1 had lower B cell proportions and numbers on D11, D14, and D21, with a difference on D11.
T cell (TCRα/β+) proportion on D7, D14, and D21 increased.
No mice were euthanized due to welfare issues or unexpected death during the experiment.
Target
CD3 & CD19
Conjugated
Unconjugated
Anwendung
ELISA, FACS, Functional assay
Chemical Information
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SMILES
[YK 012]
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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)
YK012 Related Classifications
HY-P992528 Related Classifications
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