GL-4512
GL-4512 is an orally active LILRB4/ILT3 inhibitor with an IC50 of 37 nM against human targets, and human Kd values of 18.1 nM and 39.2 nM, respectively. GL-4512 directly binds to the extracellular pockets of LILRB4/ILT3 that accommodate their ligands, blocks the LILRB4-SCG2 signaling pathway, and inhibits the downstream SHP1/SHP2 and STAT3 signaling pathways. GL-4512 restores anti-tumor immune activity, promotes the production of IFN-γ and IL-2, enhances the activation of cytotoxic T cells, reduces tumor cell viability, inhibits tumor growth, and strengthens intratumoral immune activation. GL-4512 can be used in research related to colorectal cancer and acute myeloid leukemia.
For research use only. We do not sell to patients.
- CAS No.: 1240895-94-6
- Formula: C21H23N5OS2
- Molecular Weight:425.57
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
Biological Activity
Description
IC50 & Target
[1]|
LILRB4 37 nM (IC50) |
LILRB4 18.1-39.2 nM (Kd) |
SHP1 |
SHP2 |
STAT3 |
IFN-γ |
IL-2 |
In Vitro
GL-4512 (10 μM) directly binds recombinant human LILRB4 ECD in a Dianthus/TRIC assay, with a mean ΔF_norm of 27.8% and high assay reproducibility[1].
GL-4512 (100 pM-1 μM; 15 min) binds recombinant human LILRB4 ECD with high affinity, as measured by MST, with a Kd of 18.1 nM[1].
GL-4512 (0 to 400 nM; 120 s per injection) directly binds immobilized recombinant human LILRB4 protein, as measured by SPR, with a Kd of 39.2 nM[1].
GL-4512 (0.0001-10 μM; 60 min) directly engages LILRB4 in CHO cells stably expressing human LILRB4, as measured by CETSA, with an EC50 of 53 nM[1].
GL-4512 (0.0001-10 μM; 2 h) disrupts the LILRB4-SCG2 interaction in a TR-FRET competition assay, with an IC50 of 37 nM[1].
GL-4512 (0.0001-10 μM; 1 h) suppresses SCG2-induced inhibitory signaling in THP-1-derived macrophage-like cells expressing LILRB4, with IC50 values of 101 nM for p-SHP1, 141 nM for p-SHP2, and 76.3 nM for p-STAT3[1].
GL-4512 (0.1-10 μM; 72 h) restores antitumor immune activity in cocultures of colorectal cancer patient-derived PBMCs and HCT116 cells, restoring IFN-γ and IL-2 secretion and reducing tumor cell viability[1].
GL-4512 (0.1-10 μM; 72 h) restores antitumor immune activity in cocultures of AML patient-derived PBMCs and primary AML blasts, restoring IFN-γ secretion, increasing cytotoxic T-cell activation, and reducing tumor cell viability[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:THP-1-derived macrophage-like cells expressing LILRB4
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Concentration:0.0001-10 μM
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Incubation Time:1 h
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Result:Dose-dependently suppressed SCG2-induced phosphorylation of SHP1 (IC50 = 101 nM), SHP2 (IC50 = 141 nM), and STAT3 (IC50 = 76.3 nM).
Parmacokinetics
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c (female, 6-8 weeks old, subcutaneous implantation of CT26 colorectal carcinoma cells)[1]
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Dosage:20 mg/kg
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Administration:p.o.; once daily; 21 consecutive days
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Result:Significantly suppressed tumor growth throughout the treatment period.
Substantially reduced final tumor weight compared to vehicle controls.
Significantly increased intratumoral IFN-γ and IL-2 levels relative to vehicle-treated tumors.
Showed no significant changes in body weight or overt signs of systemic toxicity during the study.
Chemical Information
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CAS No. 1240895-94-6
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Molecular Weight 425.57
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Formula C21H23N5OS2
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SMILES
O=C(C1=C(C)N=C(C2=NC=CC=N2)S1)NC3=CC=C(CN4CCSCC4)C=C3C
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)