1. Protein Tyrosine Kinase/RTK MAPK/ERK Pathway Stem Cell/Wnt JAK/STAT Signaling PI3K/Akt/mTOR
  2. FLT3 p38 MAPK STAT PI3K Akt
  3. IMC-EB10

IMC-EB10 (LY3012218) is an anti-FLT3 monoclonal antibody. IMC-EB10 binds to FLT3 with high affinity (Kd = 158 pM) and blocks the binding of FLT3 ligand to FLT3 (IC50 ≈ 10 nM), thereby inhibiting MAPK, STAT5, and PI3K/Akt signaling in leukemia cells. IMC-EB10 can enhance the anti-leukemic effect of Methotrexate (HY-14519) and inhibit leukemias expressing wild-type or ITD-mutated FLT3 receptors. IMC-EB10 prolongs the survival of acute lymphoblastic leukemia (ALL) cells and primary leukemia samples and reduces engraftment in non-obese diabetic/severe combined immunodeficiency patients. IMC-EB10 is indicated for leukemia research.

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IMC-EB10

IMC-EB10 Chemical Structure

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Description

IMC-EB10 (LY3012218) is an anti-FLT3 monoclonal antibody. IMC-EB10 binds to FLT3 with high affinity (Kd = 158 pM) and blocks the binding of FLT3 ligand to FLT3 (IC50 ≈ 10 nM), thereby inhibiting MAPK, STAT5, and PI3K/Akt signaling in leukemia cells. IMC-EB10 can enhance the anti-leukemic effect of Methotrexate (HY-14519) and inhibit leukemias expressing wild-type or ITD-mutated FLT3 receptors. IMC-EB10 prolongs the survival of acute lymphoblastic leukemia (ALL) cells and primary leukemia samples and reduces engraftment in non-obese diabetic/severe combined immunodeficiency patients. IMC-EB10 is indicated for leukemia research[1][2][3][4].

Isotype

Human IgG1 kappa

Recommend Isotype Controls
Species Reactivity

Human

IC50 & Target[1][4]

STAT5

 

In Vitro

IMC-EB10 (10 μg/mL, 1 h) reduces FLT3 and phosphorylation of downstream signaling proteins STAT5, Akt, and MAPK in Hb1119 and SEM-K2 cells, but activates them in REH and RS411 cells[1].
IMC-EB10 (10 μg/mL, 1 h) activates FLT3 and downstream Akt in ALLs[1].
IMC-EB10 (0.4-200 nM, 1 h) inhibits FLT3-Fc-induced phosphorylation of wild-type FLT3 and ligand-independent constitutive phosphorylation of ITD-mutant FLT3 in EOL-1, EM3, BaF3-ITD and MV4;11 cells[4].
IMC-EB10 (0.4-200 nM, 1 h) inhibits FLT3-Fc-induced phosphorylation of MAPK, AKT and Stat5 in EOL-1, EM3, BaF3-ITD and MV4;11 cells[4].
IMC-EB10 (1.5-100 nM, 1 h) inhibits proliferation of FLT3-Fc-induced proliferation of EOL-1 and BaF3-ITD cells[4].

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

Western Blot Analysis[1]

Cell Line: Hb1119, SEM-K2 cells
Concentration: 10 μg/mL
Incubation Time: 1 h
Result: Reduced FLT3 and phosphorylation of downstream signaling proteins STAT5, Akt, and MAPK.

Western Blot Analysis[1]

Cell Line: REH, RS411 cells
Concentration: 10 μg/mL
Incubation Time: 1 h
Result: Activated FLT3 and phosphorylation of downstream signaling proteins STAT5, Akt, and MAPK.

Western Blot Analysis[1]

Cell Line: ALLs
Concentration: 10 μg/mL
Incubation Time: 1 h
Result: Activated FLT3 and downstream Akt.

ELISA Assay[4]

Cell Line: EOL-1, EM3, BaF3-ITD, MV4;11 cells
Concentration: 0.1, 0.4, 1, 4, 10, 40, 100, 200 nM
Incubation Time: 1 h
Result: Blocked FL-induced FLT3 receptor phosphorylation in a dose dependent manner with an IC50 of 0.4 to 4 nM.
Blocked the phosphorylation and constitutive phosphorylation of MAPK, inhibited FL-induced phosphorylation of AKT and Stat5 phosphorylation in EOL-1 and BaF3-ITD cells.
In Vivo

IMC-EB10 (400 μg/10 mg/kg, i.p., thrice per week starting 24 hours after cell injection/once starting 24 hours after cell injection/a total of thrice every other day starting 24 hours after cell injection or thrice per week starting 7 days after cell injection, 30 days/2×/week, 3 weeks) reduces the presence of SEM-K2 cells, mediates cytotoxicity through natural killer cells, does not select for resistant cells, prolongs survival compared to Methotrexate (HY-14519) alone in SEM-K2 NOD/SCID mice model[1][3].
IMC-EB10 (400 μg, i.p., three times a week, 14 weeks) reduces cell implantation in ALLs NOD/SCID mice model[1].
IMC-EB10 (100-500 μg, i.p., 3 times weekly, 20 days) decreases the number of tumor cells in bone marrow and prolongs the survival in EOL-1 and BaF3-ITD xenograft leukemia model[4].

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

Animal Model: SEM-K2 (0.5×106) NOD/SCID mice model[1]
Dosage: 400 μg
Administration: i.p., thrice per week starting 24 hours after cell injection/once starting 24 hours after cell injection/a total of thrice every other day starting 24 hours after cell injection or thrice per week starting 7 days after cell injection, 30 days
Result: Reduced human cells in peripheral blood, spleen, and bone marrow, reducing the presence of SEM-K2 cells to <1%, prolonged survival. Did not select for resistant cells, mediated cytotoxicity through natural killer cells.
Animal Model: ALLs (1×106) NOD/SCID mice model[1]
Dosage: 400 μg
Administration: i.p., three times a week, 14 weeks
Result: Reduced cell implantation.
Animal Model: SEM-K2 (5×105) NOD/SCID mice model[3]
Dosage: 10 mg/kg + 100 mg/kg Methotrexate
Administration: i.p., 2×/week, 3 weeks + once per week for 3 weeks
Result: Significantly prolonged survival compared to Methotrexate alone.
Animal Model: EOL-1 (5×106) xenograft leukemia NOD/SCID mice (male, , 6-8 weeks) model[4]
Dosage: 100, 250, 500 μg
Administration: i.p., 3 times weekly, 20 days
Result: Decreased the number of tumor cells in bone marrow.
Animal Model: BaF3-ITD (5×104) xenograft leukemia NOD/SCID mice (male, , 6-8 weeks) model[4]
Dosage: 100, 500 μg
Administration: i.p., 3 times weekly
Result: Prolonged the survival.
Gene ID

2322  [NCBI]

Accession
Target

FLT3

Application

ELISA, FACS, Functional assay

Conjugated

Unconjugated

Reconsititution

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

SMILES

N/A

Storage

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

Purity & Documentation
References
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  • 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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Product Name:
IMC-EB10
Cat. No.:
HY-P991641
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