In a 10-day Z-138 xenograft study, oral UNC2250 at 50 and 75 mg/kg once daily produced reported tumor inhibition rates of 35% and 48%, respectively, relative to vehicle. The authors characterized monotherapy activity as limited. [1]
Animal effects depended on treatment context. In orthotopic pancreatic tumors, adding UNC2250 removed the survival benefit of radiotherapy plus PI3Kγ inhibition; no survival effect was reported in the non-irradiated or radiotherapy-only groups. These findings limit generalization of efferocytosis blockade as an anticancer strategy. [3]
Limited tumor-growth inhibition in a Z-138 xenograft
Animal study · Female NOD/SCID mice bearing Z-138 subcutaneous tumors; n = 6 per arm [1]
UNC2250 reduced tumor growth at 50 and 75 mg/kg over 10 days. The authors describe monotherapy effects as limited. Tumor p-MerTK decreased at these doses; body weight monitoring showed no obvious loss.
Conditions shared by the study groups
- Route
- Oral gavage
- Frequency
- Once daily
- Treatment course
- 10 days
- Vehicle
- Saline designated vehicle by authors
- 25 mg/kg UNC2250
- Model: Female NOD/SCID mice, 7–8 weeks, with Z-138 subcutaneous xenografts
- Reported limits: Drug dissolution/suspension preparation not detailed in the adopted methods.
- 50 mg/kg UNC2250
- Model: Female NOD/SCID mice, 7–8 weeks, with Z-138 subcutaneous xenografts
- Reported limits: Drug dissolution/suspension preparation not detailed in the adopted methods.
- 75 mg/kg UNC2250
- Model: Female NOD/SCID mice, 7–8 weeks, with Z-138 subcutaneous xenografts
- Reported limits: Drug dissolution/suspension preparation not detailed in the adopted methods.
Methods and source locations
Compound reported in the paper: UNC2250
Applies to the named experimental UNC2250 material; salt/stereochemical composition and Adooq lot equivalence are not independently established.
Sec9 MCL-cell-derived xenograft model; Sec17; Figure 5a–d and caption
Tumor inhibition rate relative to vehicle at termination: Caliper-based tumor-volume assessment; P = 0.021 and 0.001, respectively; n = 6 per arm; figure reports mean and SE — Sec9 MCL-cell-derived xenograft model; Sec17; Figure 5a–d and caption
Body weight and observed mortality: Body-weight monitoring; limited tolerability observation, not comprehensive toxicity assessment — Sec9 MCL-cell-derived xenograft model; Sec17; Figure 5a–d and caption
25 mg/kg UNC2250 · Sec9 MCL-cell-derived xenograft model; Sec17; Figure 5a–d and caption
50 mg/kg UNC2250 · Sec9 MCL-cell-derived xenograft model; Sec17; Figure 5a–d and caption
75 mg/kg UNC2250 · Sec9 MCL-cell-derived xenograft model; Sec17; Figure 5a–d and caption
MerTK inhibition removed combination-treatment benefit in pancreatic cancer
Animal study · Orthotopic KPC pancreatic tumors in female C57BL/6 mice; humane-endpoint survival [3]
Adding UNC2250 abrogated the survival benefit of radiotherapy plus PI3Kγ inhibition. UNC2250 did not alter survival in the non-irradiated and radiotherapy-only groups, as reported in the same results section.
Conditions shared by the study groups
- Route
- Intraperitoneal
- Frequency
- Daily
- Treatment course
- During treatment follow-up; fixed course length not specified in the read drug paragraph
- Vehicle
- 5% DMSO, 40% PEG 400, 5% Tween-20, 50% H2O
- UNC2250 added to IR + IPI-549
- Model: Orthotopic KPC pancreatic tumors in female C57BL/6 mice
- Reported limits: Group-specific survival n is not stated in the viewed Fig 6H caption; no count borrowed from another figure.
Methods and source locations
Compound reported in the paper: UNC2250
Applies to the named experimental UNC2250 material; salt/stereochemical composition and Adooq lot equivalence are not independently established.
Results: Macrophage efferocytosis is MERTK dependent; Figure 6H and caption; supplemental file 8, Animal models (PDF p. 2)
Survival response to adding UNC2250: Kaplan–Meier comparison; log-rank Mantel–Cox; experiment conducted once; no median extracted — Results: Macrophage efferocytosis is MERTK dependent; Figure 6H and caption; supplemental file 8, Animal models (PDF p. 2)
UNC2250 added to IR + IPI-549 · Results: Macrophage efferocytosis is MERTK dependent; Figure 6H and caption; supplemental file 8, Animal models (PDF p. 2)
