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| | RXC-004 Basic information |
| Product Name: | RXC-004 | | Synonyms: | RXC-004;1H-Imidazole-1-acetamide, 5-methyl-N-[5-(2-pyrazinyl)-2-pyridinyl]-4-[2-(trifluoromethyl)-4-pyridinyl]-;Zamaporvint, 10 mM in DMSO;Zamaporvint (RXC004);Zamaporvint | | CAS: | 1900754-56-4 | | MF: | C21H16F3N7O | | MW: | 439.39 | | EINECS: | | | Product Categories: | | | Mol File: | 1900754-56-4.mol |  |
| | RXC-004 Chemical Properties |
| Boiling point | 685.2±55.0 °C(Predicted) | | density | 1.43±0.1 g/cm3(Predicted) | | pka | 10.87±0.46(Predicted) | | form | Solid | | color | White to off-white |
| | RXC-004 Usage And Synthesis |
| Uses | Zamaporvint (RXC004) is an orally active and selective inhibitor of Wnt. Zamaporvint targete membrane-bound o-acyltransferase Porcupine and inhibited Wnt ligand palmitoylation, secretion, and pathway activation. Zamaporvint displays a favorable pharmacokinetic profile and shows potent antiproliferative effects in Wnt ligand-dependent colorectal and pancreatic cell lines. Zamaporvint possesses multiple antitumor mechanisms and can be used in cancer research[1]. | | in vivo | Zamaporvint (1.5 mg/kg or 5 mg/kg orally twice daily, or 5 mg/kg Zamaporvint orally once daily, for 28 days) reduces in tumor growth, and inhibition of Wnt-responsive gene expression including cMyc, was observed in the Wnt ligand–dependent SNU-1411, AsPC1, and HPAFII models, and no effected tumor growth in the Wnt ligand–independent HCT116 xenograft mode[1].
Zamaporvint (1.5 mg/kg, 5 mg/kg, once daily) reduces Ki67-positive cells in the total tumor area, and its effect is more pronounced in differentiated tumor areas, and by inhibiting immune evasion in the B16F10 "cold" tumor model Antitumor effect [1].
Zamaporvint (1.5 or 5 mg/kg once daily) stimulates host tumor immunity, reduces resident myeloid-derived suppressor cells within B16F10 tumors and synergizing with anti-programmed cell death protein-1 (PD-1, HY-P73361) to increase CD8+/regulatory T cell ratios within CT26 tumors[1].
Pharmacokinetic Parameters of Zamaporvint in Mice. [1]
| species | Dose (i.v./p.o., mg/kg) | Cmax (p.o., μM) | C24 h (p.o., μM) | AUCinf (p.o., μM.h) | Cl (mL/min/kg) | Vss (L/kg) | F (p.o., %) | T1/2 (hr) | | mouse | 2/5 | 7.6 | 0.002 | 33.9 | 2.9 | 0.40 | 48 | 1.8 | | rat | 2/5 | 3.6 | 0.009 | 10.5 | 5.8 | 0.64 | 31 | 2.5 | | dog | 2/5 | 10.4 | 0.012 | 8.6 | 8.9 | 0.39 | 137 | 0.8 |
| Animal Model: | SCID-Beige mice were dosed at Translational Drug Discovery with vehicle[1] | | Dosage: | 1.5 mg/kg or 5 mg/kg; 5 mg/kg | | Administration: | 1.5 mg/kg or 5 mg/kg orally twice daily, or 5 mg/kg RXC004 orally once daily, for 28 days | | Result: | Reduced in tumor growth, and inhibition of Wnt-responsive gene expression including cMyc, was observed in the Wnt ligand–dependent SNU-1411, AsPC1, and HPAFII models.
No effected tumor growth in the Wnt ligand–independent HCT116 xenograft mode.
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| Animal Model: | HPAF-II (5 × 106 cells; athymic nude mice), AsPC1 (3 × 106 cells; athymic nude mice), and SNU-1411 (1×107 cells; NOD-SCID mice) were implanted bilaterally, subcutaneously, whereas HCT116 (3 × 106 cells; athymic nude mice) were implanted in a single flank[1] | | Dosage: | Dosing was either 1.5 mg/kg twice daily RXC004 for 7–13 days then once daily for the remainder of study (up to 29 days), or 28 days 1.5 mg/kg twice daily RXC004 for HCT116 | | Administration: | p.o. | | Result: | Demonstrated to inhibit tumor growth and Wnt-responsive gene expression
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| Animal Model: | B16F10/C57BL/6 syngeneic model was performed at Axis Bioservices. Mouse B16F10 cells (2 × 105) were subcutaneously implanted in flanks of the immunocompetent male C57BL/6 mice[1] | | Dosage: | 5 mg/kg once daily | | Administration: | p.o. | | Result: | Inhibited tumor growth and improved model survival.
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| Animal Model: | CT26/BALB/c syngeneic model was performed at ProQuinase GmbH. Mouse CT26 cells (5 × 105) were subcutaneously implanted in the flanks of the immunocompetent female BALB/c mice[1] | | Dosage: | 1.5 or 5 mg/kg (once daily). | | Administration: | p.o. | | Result: | Increased CD8+/regulatory T cell ratio.
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| | References | [1] Phillips C, The Wnt Pathway Inhibitor RXC004 Blocks Tumor Growth and Reverses Immune Evasion in Wnt Ligand-dependent Cancer Models. Cancer Res Commun. 2022 Sep 2;2(9):914-928. DOI:10.1158/2767-9764.CRC-21-0095 |
| | RXC-004 Preparation Products And Raw materials |
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