1. GPCR/G Protein Immunology/Inflammation
  2. CCR
  3. S-531011

S-531011 is a high-affinity, selective, and reversible CCR8 ligand with antibody-dependent cellular cytotoxicity (ADCC) against CCR8-expressing cells. S-531011 induces the death of tumor-infiltrating CCR8+ regulatory T cells while preserving regulatory T cells in peripheral blood, thereby reinvigorating anti-tumor immunity. The combination of S-531011 with anti-PD-1 antibody effectively inhibits tumor growth, and S-531011 can be used for research on advanced solid tumors and various cancers including non-small cell lung cancer, ovarian cancer, colon cancer, breast cancer, and pancreatic ductal adenocarcinoma.

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S-531011

S-531011 Chemical Structure

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Description

S-531011 is a high-affinity, selective, and reversible CCR8 ligand with antibody-dependent cellular cytotoxicity (ADCC) against CCR8-expressing cells. S-531011 induces the death of tumor-infiltrating CCR8+ regulatory T cells while preserving regulatory T cells in peripheral blood, thereby reinvigorating anti-tumor immunity. The combination of S-531011 with anti-PD-1 antibody effectively inhibits tumor growth, and S-531011 can be used for research on advanced solid tumors and various cancers including non-small cell lung cancer, ovarian cancer, colon cancer, breast cancer, and pancreatic ductal adenocarcinoma[1][2][3].

Isotype

Human IgG1 kappa

Recommend Isotype Controls
Species Reactivity

Human

IC50 & Target[1]

CCR8

18.6 pM (Kd)

In Vitro

S-531011 binds to CCR8 with an in vitro-measured association rate constant of 11.9 L/nmol/hr and a calculated dissociation rate constant of 6.65 1/hr[2].
S-531011 (0.08-0.3 nmol/L; overnight) binds specifically and with high affinity to human CCR8 (Kd = 18.6 pmol/L) and its CCR8A27G variant (Kd = 26.4 pmol/L) expressed on HEK293T cells, with no cross-reactivity to other tested receptors[3].
S-531011 (up to 300 μg/mL; 2 hours) lacks CDC activity against Ramos-hCCR8 cells, with no measurable EC50 at concentrations up to 300 μg/mL[3].
S-531011 (0.001-10 μg/mL; overnight) selectively depletes tumor-infiltrating Tregs, but not Tconv cells, in human NSCLC and ovarian cancer tissues via ADCC, whereas Mogamulizumab (HY-P99253) depletes both populations[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

S-531011 (0.15-15 mg/kg; i.v.; 2 doses (days 4 and 11 post tumor inoculation)) induces potent dose-dependent antitumor activity in CT26.WT tumor-bearing hCCR8 KI mice, with significant tumor volume reduction observed at doses of 0.15, 5, and 15 mg/kg[3].
S-531011 (100 μg/mouse; i.v.; 2 doses (days 5 and 12 post tumor inoculation)) induces potent antitumor activity in EMT6 tumor-bearing hCCR8 KI mice, with significantly greater tumor volume reduction than vehicle or anti-mouse PD-1 antibody treatment[3].
S-531011 (10 mg/kg; i.v.; single dose (day 5 post tumor inoculation)) enhances the antitumor activity of anti-mouse PD-1 antibody in CT26.WT tumor-bearing hCCR8 KI mice without observable adverse effects[3].
S-531011 (0.05-5 mg/kg; i.v.; single dose (day 8 post tumor inoculation)) induces dose-dependent depletion of tumor-infiltrating CCR8+ Tregs in CT26.WT tumor-bearing hCCR8 KI mice, with effects lasting at least 7 days after a single dose[3].
S-531011 (0.05-0.5 mg/kg; i.v.; single dose (day 8 post tumor inoculation)) induces dose-dependent depletion of tumor-infiltrating CCR8+ Tregs in Colon26 tumor-bearing hCCR8 KI mice 4 days after a single dose[3].
S-531011 (0.05-0.5 mg/kg; i.v.; single dose (day 8 post tumor inoculation)) induces dose-dependent depletion of tumor-infiltrating CCR8+ Tregs in EMT6 tumor-bearing hCCR8 KI mice 4 days after a single dose[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: humanized CCR8 knock-in (hCCR8 KI) (female, CT26.WT colorectal cancer cells subcutaneously implanted)[3]
Dosage: 0.15 mg/kg; 0.5 mg/kg; 1.5 mg/kg; 5 mg/kg; 15 mg/kg
Administration: i.v.; 2 doses (days 4 and 11 post tumor inoculation)
Result: Reduced tumor volumes significantly in the 0.15, 5, and 15 mg/kg groups compared with isotype control antibody group (P < 0.05, P < 0.001, P < 0.001, respectively, on day 19 after inoculation).
Animal Model: humanized CCR8 knock-in (hCCR8 KI) (female, EMT6 mammary carcinoma cells subcutaneously implanted)[3]
Dosage: 100 μg/mouse
Administration: i.v.; 2 doses (days 5 and 12 post tumor inoculation)
Result: Reduced tumor volumes significantly compared with vehicle control group (P < 0.0001) and anti-mouse PD-1 antibody-treated group (P < 0.05) on day 28 after implantation.
Animal Model: humanized CCR8 knock-in (hCCR8 KI) (female, CT26.WT colorectal cancer cells subcutaneously implanted)[3]
Dosage: 10 mg/kg
Administration: i.v.; single dose (day 5 post tumor inoculation)
Result: Suppressed tumor volume significantly when combined with anti-mouse PD-1 antibody compared with S-531011 alone (P < 0.05) on day 21 after inoculation.
Caused no reduction in body weight or worsening of general condition.
Animal Model: humanized CCR8 knock-in (hCCR8 KI) (female, CT26.WT colorectal cancer cells subcutaneously implanted)[3]
Dosage: 0.05 mg/kg; 0.5 mg/kg; 5 mg/kg
Administration: i.v.; single dose (day 8 post tumor inoculation)
Result: Reduced the proportion of CCR8+ Tregs relative to total Tregs in a dose-dependent manner at 4 and 7 days post-administration (P < 0.001 and P < 0.0001 for all doses vs. isotype control).
Animal Model: humanized CCR8 knock-in (hCCR8 KI) (female, Colon26 colorectal cancer cells subcutaneously implanted)[3]
Dosage: 0.05 mg/kg; 0.5 mg/kg
Administration: i.v.; single dose (day 8 post tumor inoculation)
Result: Reduced the proportion of CCR8+ Tregs relative to total Tregs in a dose-dependent manner (P < 0.05 for 0.05 mg/kg, P < 0.01 for 0.5 mg/kg vs. saline) 4 days after administration.
Animal Model: humanized CCR8 knock-in (hCCR8 KI) (female, EMT6 mammary carcinoma cells subcutaneously implanted)[3]
Dosage: 0.05 mg/kg; 0.5 mg/kg
Administration: i.v.; single dose (day 8 post tumor inoculation)
Result: Reduced the proportion of CCR8+ Tregs relative to total Tregs in a dose-dependent manner (P < 0.05 for 0.05 mg/kg, P < 0.01 for 0.5 mg/kg vs. saline) 4 days after administration.
Clinical Trial
Gene ID

1237  [NCBI]

Accession
Application

ELISA, FACS, Functional assay

Conjugated

Unconjugated

Reconsititution

The product can be reconstituted/diluted with sterile PBS or saline.

Molecular Weight

148.11 kDa

Appearance

Liquid

Color

Colorless to light yellow

SMILES

[S-531011]

Shipping

Shipping with dry ice.

Formulation

Please refer to the lot-specific COA for specific buffer information.

Storage

Please store the product under the recommended conditions in the Certificate of Analysis.

Purity & Documentation
References
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Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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S-531011
Cat. No.:
HY-P991481
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