2. Immunology/Inflammation
  3. CD47
  4. Evorpacept

Evorpacept  (Synonyms: ALX148)

Cat. No.: HY-P99950 Purity: 99.75%
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Evorpacept (ALX148) is a high-affinity CD47-blocking fusion protein with an inactive human immunoglobulin Fc region. Evorpacept binds to CD47, blocks the interaction of the CD47-SIRPα immune checkpoint, and inhibits the binding of wild-type SIRPα to CD47. Evorpacept is applicable to research related to acute myeloid leukemia.

For research use only. We do not sell to patients.

CAS No. : 2484949-51-9

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Description

Evorpacept (ALX148) is a high-affinity CD47-blocking fusion protein with an inactive human immunoglobulin Fc region. Evorpacept binds to CD47, blocks the interaction of the CD47-SIRPα immune checkpoint, and inhibits the binding of wild-type SIRPα to CD47. Evorpacept is applicable to research related to acute myeloid leukemia[1][2][3][4].

IC50 & Target

CD47
In Vitro

Evorpacept (ALX148) binds human, cynomolgus monkey, mouse, and rat CD47-ECD with high affinity, with a picomolar affinity for human CD47 at 25°C (Kd = 140 pM)[1].
Evorpacept (ALX148) (20 nM; 15 min on ice) binds to CD47 expressed on the surface of OE19, DLD-1, MM1.R, Raji, Z138, Daudi, CT26, and MC38 tumor cells[1].
Evorpacept (ALX148) (12.5 nM; 15 min on ice) blocks over 90% of wild-type SIRPα binding to CD47 on Jurkat tumor cells[1].
Evorpacept (ALX148) does not bind human FcγRI, FcγRIIA, FcγRIIB/C, or FcγRIIIA, but binds human FcRn with a Kd of ~580 nM at 25°C[1].
Evorpacept (ALX148) (6 h at 37°C) does not induce antibody-dependent cellular cytotoxicity (ADCC) activity in a cell-based reporter assay with Raji target cells and Jurkat effector cells[1].
Evorpacept (ALX148) (5 μg/mL; overnight) does not bind human complement C1q in an ELISA assay[1].
Evorpacept (ALX148) (0.25-500 nM; 4 h at room temperature) does not induce hemagglutination of human erythrocytes[1].
Evorpacept (ALX148) (0.001-1000 nM; 2 h at 37°C) enhances antibody-dependent phagocytosis of OE19, DLD-1, MM1.R, and Daudi tumor cells by human monocyte-derived macrophages when combined with trastuzumab, cetuximab, daratumumab, or obinutuzumab, respectively[1].

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

Evorpacept Related Antibodies
In Vivo

Evorpacept (ALX148) (30 mg/kg; i.v.; single dose) causes no adverse changes in hematologic parameters compared to baseline in female CD-1 Mus musculus[1].
Evorpacept (ALX148) (i.p.; twice weekly; three weeks) in combination with obinutuzumab significantly enhances tumor growth inhibition in female NOD-SCID mice bearing Z138 B-cell mantle cell lymphoma xenografts, compared to obinutuzumab alone[1].
Evorpacept (ALX148) (i.p.; twice weekly; three weeks) in combination with trastuzumab significantly enhances tumor growth inhibition in female NOD-SCID mice bearing OE19 gastroesophageal cancer xenografts, compared to trastuzumab alone[1].
Evorpacept (ALX148) (i.p.; twice weekly; three weeks) in combination with rituximab significantly enhances tumor growth inhibition and survival in female NOD-SCID mice bearing Raji B-cell lymphoma xenografts, compared to rituximab alone or PBS[1].
Evorpacept (ALX148) (30 mg/kg; i.p.; two doses; 10 days apart) enhances the antitumor efficacy of anti-PD-L1 in female C57BL/6 mice bearing MC38 colon carcinoma, driving significant tumor growth inhibition, prolonged survival, and a robust intratumoral adaptive immune response[1].
Evorpacept (ALX148) (30 mg/kg; i.p.; single dose) modulates innate and adaptive immune responses, and enhances the antitumor efficacy of anti-PD-1 in female BALB/c mice bearing CT26 colon carcinoma, driving significant tumor growth inhibition, prolonged survival, and reduced immune suppression in the tumor microenvironment[1].
Evorpacept (ALX148) (10-30 mg/kg; i.p.; single dose) achieves dose-dependent CD47 occupancy in splenic and tumor tissues of female BALB/c mice bearing CT26-M/H HER2 tumors, with 30 mg/kg achieving near-maximal tumor CD47 occupancy and prolonged systemic exposure[1].
Evorpacept (ALX148) (i.p.; two doses; 5 days apart) in combination with anti-4-1BB significantly enhances survival in female BALB/c mice bearing CT26 colon carcinoma, compared to PBS[1].
Evorpacept (ALX148) (10-30 mg/kg; i.v.; single dose) achieves complete CD47 occupancy on circulating T lymphocytes, with dose-dependent persistence of occupancy in female cynomolgus monkeys[1].
Evorpacept in combination with rituximab significantly enhances tumor growth inhibition and survival in murine xenograft models of human B-cell non-Hodgkin lymphoma, while single-agent evorpacept shows minimal efficacy[3].
Evorpacept in combination with trastuzumab or obinutuzumab significantly enhances tumor growth inhibition and survival in murine xenograft models of human gastric and colon cancer, while single-agent evorpacept shows minimal efficacy[3].
Evorpacept in combination with anti-PD-L1 or anti-4-1BB significantly enhances anti-tumor activity in immunocompetent syngeneic tumor models, while single-agent evorpacept shows limited efficacy; evorpacept also shifts tumor-associated macrophages towards an anti-tumor phenotype in CT26 tumors[3].
Evorpacept does not reduce red blood cell, platelet, or white blood cell levels in normal mice, unlike a control protein with an active Fc domain[3].
Evorpacept does not alter red blood cell, white blood cell, or platelet levels in normal cynomolgus monkeys[3].

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

Animal Model: CD-1 (female, 6-8 weeks old)[1]
Dosage: 30 mg/kg
Administration: i.v.; single dose
Result: Maintained levels of red blood cells, platelets, and white blood cells (lymphocytes, monocytes, granulocytes) similar to predose baseline values at 72, 120, and 240 hours post-dose.
Animal Model: C57BL/6 (female, 6-8 weeks old, subcutaneous implantation of 0.5×106 MC38 tumor cells)[1]
Dosage: 30 mg/kg
Administration: i.p.; two doses; 10 days apart
Result: Showed minimal single-agent tumor growth inhibition.
Resulted in significantly enhanced tumor growth inhibition compared to anti-PD-L1 alone.
Significantly increased survival compared to PBS.
Significantly increased tumor-infiltrating CD8+ T cells, CD4+ T cells, effector memory CD8+ T cells, effector memory CD4+ T cells, IFNγ-expressing CD8+ T cells, and granzyme B-expressing CD8+ T cells compared to vehicle control.
Animal Model: BALB/c (female, 6-8 weeks old, subcutaneous implantation of 0.5×106 CT26 tumor cells)[1]
Dosage: 30 mg/kg
Administration: i.p.; single dose
Result: Showed minimal single-agent tumor growth inhibition.
Resulted in significantly enhanced tumor growth inhibition compared to anti-PD-1 alone.
Significantly increased survival.
Resulted in a nearly 3-fold increase in the ratio of M1 to M2 tumor-associated macrophages and a 4-fold decrease in splenic CD8- dendritic cells (DCs) compared to vehicle control.
Upregulated the activation marker CD86 on splenic CD8+ and CD8- DCs, increased splenic effector memory CD4+ T cells, central memory CD4+ T cells, central memory CD8+ T cells, KLRG1 expression on CD8+ T cells, and AH1-specific tumor-reactive CD8+ T cells compared to vehicle control.
Resulted in a 2.5-fold increase in the M1 to M2 macrophage ratio, a 1.7-fold decrease in monocytic myeloid-derived suppressor cells, a 2.2-fold increase in splenic CD8+ DCs, and increased IFNγ expression in tumor-infiltrating CD8+ T cells.
Application

ELISA, FACS, Functional assay
Conjugated

Unconjugated
Reconsititution

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

76.61 kDa

CAS No.
Appearance

Liquid

Color

Colorless to light yellow

SMILES

[Evorpacept]
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.
Format
  • Homo sapiens SIRPA (signal regulatory protein alpha, SHPS1, SIRP, SIRPalpha)-IGHG1 (Fc (Fragment constant)
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.

Keywords:

Evorpacept2484949-51-9ALX148ALX 148ALX-148CD47Cluster of Differentiation 47MER6OA3gastric cancerSIRPαtumor-associated macrophagesdendritic cellacute myeloid leukemiab-cell mantle cell lymphomaT cellcolon carcinomab-cell lymphomaInhibitorinhibitorinhibit

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