nod/scid

Avatrombopag (YM477) is a new oral thrombopoietin (TPO) receptor agonist, activating TPO receptor and increasing megakaryocytic proliferation differentiation and platelet production.

ART838 is a dimeric pimeloyl urea compound notable for its potent anti-leukemic activity and favorable pharmacological properties. In vitro, ART-838 exhibits submicromolar inhibitory concentrations against all leukemia cell lines, demonstrating anti-leukemic efficacy 88 times greater than artemether. This compound remains in the body for extended periods and works synergistically with other anti-leukemic agents and novel kinase inhibitors to suppress leukemia cell growth. In immunodeficient NOD-SCID-IL2Rgnull (NSG) mice, ART-838 attains a plasma half-life longer than that of artemether, sustaining effective anti-leukemic concentrations for over 8 hours. Intermittent ART-838 treatment notably inhibited the growth of acute leukemia xenografts and primary grafts in NSG mice, surpassing the efficacy of artemether.

SW203668 is an irreversible inhibitor of stearoyl-CoA desaturase (IC50 = 54 nM). It is selectively cytotoxic to H2122, H460, HCC44, and HCC95 cell lines that express cytochrome P450 (CYP) isoform CYP4F11 over eight other cancer cell lines that lack CYP4F11 in vitro (IC50s = 22-116 and >10,000 nM, respectively) and ectopic expression of CYP4F11 in SW203668-insensitive H1155 cells results in sensitization to SW203668. In vivo, SW203668 reduces tumor growth rate without reducing sebocyte production in the H2122 wild-type and nonobese diabetic severe combined immunodeficiency (NOD-SCID) mouse xenograft models when administered at doses of 20 and 6 mg/kg, respectively.

AD4, an artemisinin derivative functioning as a proteolytic targeting chimera (PROTAC) for PCLAF, effectively degrades PCLAF in RS4;11 cells with an IC50 of 0.6 nM. This degradation activates the p21 Rb axis, resulting in antitumor activity. Furthermore, AD4 has been demonstrated to prolong survival in NOD SCID mice transplanted with RS4;11 cells, showcasing its in vivo efficacy [1].