PKHB1 (txCD47) is a CD47 agonist and Thrombospondin-1 peptide mimetic. PKHB1 activates CD47 and triggers Caspase -independent, calcium-dependent cell death via mitochondrial alterations, ROS production, endoplasmic reticulum morphological changes, and dissipation of mitochondrial membrane potential. PKHB1 induces the exposure of Calreticulin, HSP70, and HSP90, thereby driving immunogenic cell death. PKHB1 promotes intratumoral CD8 + T cell infiltration and inhibits breast tumorigenesis. PKHB1 reduces HSV-1 levels and alleviates the severity of herpes simplex keratitis. PKHB1 can be used in research related to breast cancer, herpes simplex keratitis, and T-cell acute lymphoblastic leukemia [1] [2] [3].
In Vivo, PKHB1 (400 μg; i.p.; once daily) exhibits in vivo anti-tumor efficacy against 4T1 breast cancer in BALB/c mice, while promoting intratumoral CD8+ T cell infiltration and reducing immunosuppressive cell populations[1]. PKHB1 (200 µM; subconjunctival injection; 1 day before infection, 1 day after infection, 2 days after infection) prolongs the survival of mice with herpes simplex keratitis (HSK), reduces the replication level of HSV-1 in ocular tissues, alleviates the severity of HSK, and enhances the antiviral immune response by increasing the recruitment of antigen-presenting cells and CD8+ T cells[2]. PKHB1 (200 μg; intraperitoneal injection; once weekly for 6 consecutive weeks) induces complete tumor regression in L5178Y-R tumor-bearing BALB/c mice, restores white blood cell counts to healthy levels, and provides long-term anti-tumor protection, resulting in a 90% survival rate in mice after secondary challenge[3].
In Vitro, PKHB1 (100-400 μM; 2 h) induces concentration-dependent cell death in MCF-7, MDA-MB-231 and 4T1 breast cancer cells, with CC50 values of approximately 200 μM, 200 μM and 300 μM, respectively[1]. PKHB1 (200-300 μM; 2 h) induces loss of mitochondrial membrane potential, ROS production, and intracellular Ca2+ accumulation in MCF-7, MDA-MB-231, and 4T1 breast cancer cells at its CC50 concentration[1]. PKHB1 (200-300 μM; 2 h) induces the surface exposure of CALR, HSP70 and HSP90 on MCF-7, MDA-MB-231 and 4T1 breast cancer cells at its CC50 concentration[1]. The PKHB1 peptide (0-500 μM; 24 h) exhibits low cytotoxicity against HCECs, B4G12 cells, RAW264.7 cells, and THP1 cells[2]. At a concentration of 100 μM, the PKHB1 peptide does not directly inhibit HSV-1 replication in HSV-1-infected HCECs in the absence of immune cells[2]. PKHB1 (200 μM; 2 h) induces caspase-independent, calcium-dependent cell death and mitochondrial transmembrane potential loss in CCRF-CEM, MOLT-4 and L5178Y-R cells[3]. Incubation with PKHB1 (200-300 μM; 2 h) at the CC50 concentration for 2 hours across various cell lines induces significant calreticulin exposure on the surface of CCRF-CEM, MOLT-4 and L5178Y-R cells[3].
References:
[1]. Calvillo-Rodríguez KM, et al. PKHB1, a thrombospondin-1 peptide mimic, induces anti-tumor effect through immunogenic cell death induction in breast cancer cells. Oncoimmunology. 2022;11(1):2054305. Published 2022 Apr 4.
[2]. He Y, et al. PKHB1 peptide induces antiviral effects through induction of immunogenic cell death in herpes simplex keratitis. Front Pharmacol. 2022;13:1048978. Published 2022 Dec 1.
[3]. Uscanga-Palomeque AC, et al. CD47 agonist peptide PKHB1 induces immunogenic cell death in T-cell acute lymphoblastic leukemia cells. Cancer Sci. 2019;110(1):256-268.
In Vivo, PKHB1 (400 μg; i.p.; once daily) exhibits in vivo anti-tumor efficacy against 4T1 breast cancer in BALB/c mice, while promoting intratumoral CD8+ T cell infiltration and reducing immunosuppressive cell populations[1]. PKHB1 (200 µM; subconjunctival injection; 1 day before infection, 1 day after infection, 2 days after infection) prolongs the survival of mice with herpes simplex keratitis (HSK), reduces the replication level of HSV-1 in ocular tissues, alleviates the severity of HSK, and enhances the antiviral immune response by increasing the recruitment of antigen-presenting cells and CD8+ T cells[2]. PKHB1 (200 μg; intraperitoneal injection; once weekly for 6 consecutive weeks) induces complete tumor regression in L5178Y-R tumor-bearing BALB/c mice, restores white blood cell counts to healthy levels, and provides long-term anti-tumor protection, resulting in a 90% survival rate in mice after secondary challenge[3].
In Vitro, PKHB1 (100-400 μM; 2 h) induces concentration-dependent cell death in MCF-7, MDA-MB-231 and 4T1 breast cancer cells, with CC50 values of approximately 200 μM, 200 μM and 300 μM, respectively[1]. PKHB1 (200-300 μM; 2 h) induces loss of mitochondrial membrane potential, ROS production, and intracellular Ca2+ accumulation in MCF-7, MDA-MB-231, and 4T1 breast cancer cells at its CC50 concentration[1]. PKHB1 (200-300 μM; 2 h) induces the surface exposure of CALR, HSP70 and HSP90 on MCF-7, MDA-MB-231 and 4T1 breast cancer cells at its CC50 concentration[1]. The PKHB1 peptide (0-500 μM; 24 h) exhibits low cytotoxicity against HCECs, B4G12 cells, RAW264.7 cells, and THP1 cells[2]. At a concentration of 100 μM, the PKHB1 peptide does not directly inhibit HSV-1 replication in HSV-1-infected HCECs in the absence of immune cells[2]. PKHB1 (200 μM; 2 h) induces caspase-independent, calcium-dependent cell death and mitochondrial transmembrane potential loss in CCRF-CEM, MOLT-4 and L5178Y-R cells[3]. Incubation with PKHB1 (200-300 μM; 2 h) at the CC50 concentration for 2 hours across various cell lines induces significant calreticulin exposure on the surface of CCRF-CEM, MOLT-4 and L5178Y-R cells[3].
References:
[1]. Calvillo-Rodríguez KM, et al. PKHB1, a thrombospondin-1 peptide mimic, induces anti-tumor effect through immunogenic cell death induction in breast cancer cells. Oncoimmunology. 2022;11(1):2054305. Published 2022 Apr 4.
[2]. He Y, et al. PKHB1 peptide induces antiviral effects through induction of immunogenic cell death in herpes simplex keratitis. Front Pharmacol. 2022;13:1048978. Published 2022 Dec 1.
[3]. Uscanga-Palomeque AC, et al. CD47 agonist peptide PKHB1 induces immunogenic cell death in T-cell acute lymphoblastic leukemia cells. Cancer Sci. 2019;110(1):256-268.