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.

APD-94 is a dual inhibitor targeting tubulin and Bmi-1. It disrupts the normal polymerization of tubulin and suppresses the expression of Bmi-1. This compound induces cell cycle arrest at the G2/M phase and triggers apoptosis, thereby inhibiting cancer cell proliferation. Additionally, APD-94 inhibits the growth of HT29 cell xenograft tumors in NOD/SCID mice and is applicable to colorectal cancer research.

FLT3-IN-32 is a potent FLT3 inhibitor with high selectivity, effectively suppressing FLT3 activating mutations and inducing apoptosis. It demonstrates good tolerance in non-tumor-bearing mice. In NOD/SCID mice loaded with MV4-11 cells, FLT3-IN-32 exhibits outstanding antitumor efficacy, significantly extending mouse survival. FLT3-IN-32 is applicable for acute myeloid leukemia research.

TQ-3959 is an orally active BTKPROTAC degrader, with a DC50 of 14.6 nM. It exhibits antiproliferative activity against both wild-type BTK and BTK C481S mutant cell lines. TQ-3959 demonstrates tumor growth inhibition in female NOD-SCID mice with TMD-8 xenografts. This compound is applicable in the study of B-cell malignancies, such as lymphoma.

PROTACFLT3/JAK2/BRD4 Degrader-1 is a PROTAC degrader targeting FLT3, JAK2, and BRD4, with DC50 values of 5.23 nM, 0.678 nM, and 1.17 nM, respectively. It exhibits potent antiproliferative activity against MV4;11 cells (IC50= 0.79 nM) and FLT3-mutated Ba/F3 cells. Additionally, PROTACFLT3/JAK2/BRD4 Degrader-1 induces apoptosis in MV4;11 cells and demonstrates significant antitumor efficacy in an MV4;11 xenograft model established in NOD SCID mice. This compound is applicable for research in acute myeloid leukemia (AML).

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 is an artemisinin-derived proteolysis targeting chimera that selectively degrades PCLAF protein with subnanomolar potency in RS4;11 leukemia cells,AD4 leads to activation of the p21/Rb signaling axis, robust anti-tumor activity, and significantly prolonged survival in RS4;11 xenograft NOD/SCID mouse models, demonstrating both in vitro and in vivo therapeutic efficacy.