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  3. INCA033989

INCA033989 is a fully human IgG1 monoclonal antibody targeting mutCALR (KD = 1.75 nM for mutCALRdel52; KD = 6.78 nM for mutCALRins5). INCA033989 antagonizes mutCALR-driven signaling and proliferation. INCA033989 selectively inhibits pSTAT3/pSTAT5. INCA033989 prevents thrombocytosis and reduces the expansion of mutCALR-positive cells. INCA033989 is useful for research on myeloproliferative neoplasms .

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INCA033989

INCA033989 Chemical Structure

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Description

INCA033989 is a fully human IgG1 monoclonal antibody targeting mutCALR (KD = 1.75 nM for mutCALRdel52; KD = 6.78 nM for mutCALRins5). INCA033989 antagonizes mutCALR-driven signaling and proliferation. INCA033989 selectively inhibits pSTAT3/pSTAT5. INCA033989 prevents thrombocytosis and reduces the expansion of mutCALR-positive cells. INCA033989 is useful for research on myeloproliferative neoplasms [1].

Species Reactivity

Human

IC50 & Target

STAT3

 

STAT5

 

In Vitro

INCA033989 binds to recombinant mutCALRdel52 and mutCALRins5 proteins with nanomolar affinities (KD = 1.75 nM for mutCALRdel52; 6.78 nM for mutCALRins5), showing slight preferential binding to mutCALRdel52[1].
INCA033989 (72 h) selectively inhibits cytokine-independent proliferation of Ba/F3-TPOR/CALRdel52 and UT-7-TPOR/CALRdel52 cells (IC50 = 0.1 μg/mL; IC90 = 1 μg/mL)[1].
INCA033989 (4 h) broadly inhibits mutCALR-driven oncogenic signaling (including pSTAT5) in Ba/F3-TPOR/CALRdel52 cells[1].
INCA033989 (4 h) does not induce complement-dependent cytotoxicity in TF-1-TPOR/CALRdel52 cells[1].

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

In Vivo

INCA033989 (10 mg/kg; i.p.; single dose) reduces Ba/F3-TPOR/CALRdel52 cell burden in NOD scid gamma (NSG) mice model of Myeloproliferative neoplasm (with a plasma concentration of 50 μg/mL)[1].
INCA033989 (3-10 mg/kg; i.p.; twice weekly; 10 weeks) prevents thrombocytosis, reduces mutCALR-positive cell expansion, and normalizes bone marrow histology in C57BL/6 (CD45.2+; lethally irradiated recipients), CD45.2+ floxed homozygous CALRdel52 KI, CD45.2+ wt transgenic (UBI-GFP/BL6) mice model of Myeloproliferative neoplasm [1].

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

Animal Model: NOD scid gamma (NSG)[1]
Dosage: 10 mg/kg
Administration: i.p.; single dose
Result: Decreased numbers of Ba/F3 cells in the blood, reduced spleen weight compared to isotype control, and achieved a plasma concentration of 50 μg/mL on day 13
Animal Model: C57BL/6 (CD45.2+; lethally irradiated recipients); CD45.2+ floxed homozygous CALRdel52 KI; CD45.2+ wt transgenic (UBI-GFP/BL6)[1]
Dosage: 3-10 mg/kg
Administration: i.p.; twice weekly; 10 weeks
Result: Prevented thrombocytosis with platelet counts remaining within normal range, inhibited expansion of mutCALR-positive platelets (36% vs 96% in isotype control), reduced mutCALR-positive long-term hematopoietic stem cells (32% vs 85% in isotype control), and normalized bone marrow histology with normal megakaryocyte numbers
Clinical Trial
Gene ID

811  [NCBI]

Accession

P27797

Application

ELISA, FACS, Functional assay

Conjugated

Unconjugated

Reconsititution

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

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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INCA033989
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HY-P991888
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