PF-06747143
PF-06747143 is recombinant anti-human antibody targeting CXCR4. PF-06747143 blocks CXCL12-induced calcium flux, F-actin polymerization, chemotaxis, cell migration, and leukemic cell bone marrow homing. PF-06747143 reduces tumor burden and improves survival in mouse models of hematologic malignancies. PF-06747143 can be used for the research of chronic lymphocytic leukemia, acute myeloid leukemia, and hematologic malignancies.
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Activité biologique
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Chemical Information
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- Références
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Help & FAQs
Activité biologique
Human IgG1 kappa
Human
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CXCR4 |
PF-06747143 (20 μg/mL) binds specifically to human CXCR4-expressing CHO-hCXCR4 cells, with no binding to CXCR4-negative CHO-parental cells[1].
PF-06747143 (110 min) potently inhibits CXCL12-induced calcium flux in Jurkat cells with an IC50 of 1.41 nM, and this inhibitory activity does not require antibody bivalency or the Fc region[1].
PF-06747143 (10-1000 nM; 48 h) induces bivalency-dependent cell death in patient-derived primary CLL-B cells, with activity independent of stromal cell support, CLL prognostic risk factors, or TP53 status, and minimal effect on normal B and T lymphocytes[1].
PF-06747143 (100 nM; 48 h) induces caspase-independent cell death in patient-derived primary CLL-B cells[1].
PF-06747143 (100 nM) induces bivalency-dependent ROS production and subsequent cell death in patient-derived primary CLL-B cells, with ROS levels comparable to the programmed cell death-inducing antibody obinutuzumab[1].
PF-06747143 (10-1000 nM) potently inhibits CXCL12-induced F-actin polymerization in primary CLL-B cells, with 100 and 1000 nM reducing polymerization below baseline levels[1].
PF-06747143 (10 nM-1 μM; 1 h pre-incubation) dose-dependently inhibits CXCL12-induced migration of primary CLL-B cells[1].
PF-06747143 (0.2-2000 nM; 4 h) induces dose-dependent complement-dependent cytotoxicity in primary CLL-B cells, with significantly greater activity in the presence of active complement[1].
PF-06747143 induces potent antibody-dependent cell-mediated cytotoxicity in primary CLL-B cells and JVM-13 CLL tumor cells, with activity dependent on the IgG1 Fc region[1].
PF-06747143 significantly inhibits CXCL12-induced chemotaxis in primary AML cells[2].
PF-06747143 (65 nM; 4-5 h) potently inhibits CXCL12-driven migration of HL-60, U937, and primary AML cells[3].
PF-06747143 (0-100 nM; 4 h) induces dose-dependent ADCC-mediated cytotoxicity in primary AML BM cells and MV4-11 cells via Fc-effector function, with activity dependent on CXCR4 expression[3].
PF-06747143 functionally antagonizes CXCL12-induced CXCR4 signaling in CHO-K1-CXCR4 cells with an EC50 of 7.75 nM[4].
PF-06747143 (24 h) potently inhibits CXCL12-induced migration of Ramos human NHL cells with an IC50 of 0.24 nM, and also inhibits migration of MV4-11 AML cells[4].
PF-06747143 (4 h) induces potent ADCC against Ramos human NHL cells with an IC50 of 115 pM[4].
PF-06747143 (100 nM; 4 h) induces ADCC-mediated cell death in MV4-11 human AML cells and OPM-2 human MM cells[4].
PF-06747143 (33 nM; 4 h) induces CDC-mediated cell lysis in Daudi human NHL cells[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:primary CLL-B cells
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Concentration:10; 100; 1000 nM
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Incubation Time:1 h pre-incubation
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Result:Significantly inhibited cell migration in a range from 40 to 80%, relative to CXCL12 induction only.
Inhibited cell migration in a dose dependent manner.
PF-06747143 (10 mg/kg; s.c.; weekly for 7 weeks; or single dose) inhibits tumor growth and extends median survival in the P17CXCR4-low AML mouse PDX model[3].
PF-06747143 (10 mg/kg; s.c.; weekly; 5 weeks) inhibits leukemia growth and extends median survival in the P15CXCR4-high AML mouse PDX model[3].
PF-06747143 (0.1-30 mg/kg; s.c.; weekly; 2-4 doses) induces dose-dependent tumor growth inhibition in a subcutaneous NHL xenograft model[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:SCID beige (female, disseminated chronic lymphocytic leukemia model via tail vein injection of luciferase-expressing JVM-13 CLL cells)[1]
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Dosage:10 mg/kg
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Administration:s.c.; once weekly; 6 doses
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Result:Reduced tumor burden compared to IgG1 control.
Extended median survival to 68.5 days.
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Animal Model:NSG mice (immunodeficient)[3]
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Dosage:10 mg/kg mobilization study)
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Administration:s.c.; weekly for 7 weeks; or single dose
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Result:Significantly reduced the percentage and absolute number of hCD45+ leukemic cells in peripheral blood after 2 weeks of treatment, with sustained reductions in bone marrow, spleen, and peripheral blood at study end (7 weeks).
Extended median survival to 167 days, compared to 113 days for control mice.
Reduced density of AML cells in bone marrow, spleen, and liver relative to controls.
Resulted in significantly lower peripheral blood leukemic cell percentages at 14 weeks post-secondary transplantation, and extended secondary mice median survival to 165.5 days, compared to 138 days for mice receiving control-treated cells.
Induced rapid mobilization: absolute leukemic cell numbers increased in peripheral blood and decreased in bone marrow 4 hours post-injection.
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Animal Model:NSG mice (immunodeficient)[3]
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Dosage:10 mg/kg
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Administration:s.c.; weekly; 5 weeks
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Result:Prevented increases in peripheral blood leukemic cell percentages and absolute numbers, with sustained reductions in bone marrow, spleen, and peripheral blood at study end.
Showed leukemic burden significantly lower than both control in all tissues.
Extended median survival to 156 days.
Reduced density of AML cells in bone marrow, spleen, and liver relative to control.
Resulted in significantly lower peripheral blood leukemic cell percentages at 8 weeks post-secondary transplantation compared to control.
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Animal Model:SCID beige (female)[4]
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Dosage:0.1; 1; 10; 30 mg/kg
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Administration:s.c.; weekly; 2-4 doses
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Result:Induced tumor regressions in 70% of animals at 10 mg/kg, with tumor volumes below initial sizes at the end of the study.
Showed similar sustained tumor growth inhibition relative to initial tumor volume at 10 mg/kg and 30 mg/kg through day 38, even after treatment suspension on day 21.
CXCR4/CD184
Unconjugated
The product can be reconstituted/diluted with sterile PBS or saline.
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Product Image
ELISA, FACS, Functional assay
Chemical Information
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Formulation
Please refer to the lot-specific COA for specific buffer information.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
[1]. Kashyap MK, et al. Targeting the CXCR4 pathway using a novel anti-CXCR4 IgG1 antibody (PF-06747143) in chronic lymphocytic leukemia. J Hematol Oncol. 2017;10(1):112. Published 2017 May 19. [Content Brief]
[2]. Zhang Y, et al. Targeting primary acute myeloid leukemia with a new CXCR4 antagonist IgG1 antibody (PF-06747143). Sci Rep. 2017 Aug 4;7(1):7305. [Content Brief]
[3]. Zhang Y, et al. Targeting primary acute myeloid leukemia with a new CXCR4 antagonist IgG1 antibody (PF-06747143). Sci Rep. 2017;7(1):7305. Published 2017 Aug 4. [Content Brief]
[4]. Liu SH, et al. A novel CXCR4 antagonist IgG1 antibody (PF-06747143) for the treatment of hematologic malignancies. Blood Adv. 2017;1(15):1088-1100. Published 2017 Jun 21. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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