Bentamapimod (AS 602801) induces cell death in a dose-dependent manner across various cancer cell lines including human pancreatic, non-small cell lung, ovarian cancer, and glioblastoma cells, without affecting the viability of normal human fibroblasts. It also hinders the self-renewal and tumor-initiating capabilities of cancer stem cells that survive treatment with Bentamapimod (AS 602801)[2].
体内研究
Treatment of nude mice bearing xenografts from women with endometriosis (BWE) with 30 mg/kg Bentamapimod (AS 602801) results in a 29% reduction in lesion size. Neither Medroxyprogesterone acetate (MPA) nor progesterone (PR) alone reduced BWE lesions; however, combining 10 mg/kg Bentamapimod with MPA achieved a 38% lesion regression. In human endometrial organ cultures from healthy women, both Bentamapimod and MPA decrease matrix metalloproteinase-3 (MMP-3) release. In BWE organ cultures, PR and MPA do not inhibit MMP-3 secretion, while AS 602801 alone or combined with MPA reduces MMP-3 production. In an autologous rat endometriosis model, AS 602801 reduces lesions by 48% compared to 84% with the GnRH antagonist Antide. Bentamapimod also lowers inflammatory cytokines in endometriotic lesions and enhances natural killer cell activity without negatively affecting the uterus[3].
体外研究
Bentamapimod (AS 602801) induces cell death in a dose-dependent manner across various cancer cell lines including human pancreatic, non-small cell lung, ovarian cancer, and glioblastoma cells, without affecting the viability of normal human fibroblasts. It also hinders the self-renewal and tumor-initiating capabilities of cancer stem cells that survive treatment with Bentamapimod (AS 602801)[2].
AS602801 showed cytotoxicity against patient-derived glioblastoma stem cells
Oncotarget. 2016 May 10;7(19):27021-32.
A2780 CSLCs ovarian cancer stem cells
7.5 μM
3 days
AS602801 showed cytotoxicity against ovarian cancer stem cells, with sensitivity comparable to the original cell lines
Oncotarget. 2016 May 10;7(19):27021-32.
A549 CSLCs lung cancer stem cells
7.5 μM
3 days
AS602801 showed cytotoxicity against lung cancer stem cells, with sensitivity comparable to the original cell lines
Oncotarget. 2016 May 10;7(19):27021-32.
PANC-1 CSLCs pancreatic cancer stem cells
7.5 μM
3 days
AS602801 showed cytotoxicity against pancreatic cancer stem cells, with sensitivity comparable to the original cell lines
Oncotarget. 2016 May 10;7(19):27021-32.
A2780 ovarian cancer cells
7.5 μM
3 days
AS602801 induced cell death and reduced viable cell numbers, showing selective cytotoxicity against ovarian cancer cells
Oncotarget. 2016 May 10;7(19):27021-32.
A549 lung cancer cells
7.5 μM
3 days
AS602801 induced cell death and reduced viable cell numbers, showing selective cytotoxicity against lung cancer cells
Oncotarget. 2016 May 10;7(19):27021-32.
PANC-1 pancreatic cancer cells
7.5 μM
3 days
AS602801 induced cell death and reduced viable cell numbers, showing selective cytotoxicity against pancreatic cancer cells
Oncotarget. 2016 May 10;7(19):27021-32.
IMR90 normal human fibroblasts
10 μM
3 days
Evaluate the toxicity of AS602801 on non-neoplastic cells, showing no significant toxicity at 10 μM
Oncotarget. 2016 May 10;7(19):27021-32.
Human endometrial organ cultures (from women with endometriosis)
5 or 15 μM
72 h
To evaluate the effect of AS602801 on MMP-3 release. Results showed that AS602801 alone or in combination with MPA suppressed MMP-3 production, while PR or MPA alone failed.
Reprod Sci. 2016 Jan;23(1):11-23.
Human endometrial organ cultures (from healthy women)
5 or 15 μM
72 h
To evaluate the effect of AS602801 on MMP-3 release. Results showed that AS602801 alone or in combination with MPA reduced MMP-3 release.
Reprod Sci. 2016 Jan;23(1):11-23.
human vestibular schwannoma cells
2, 20, 50 µM
24 h
AS602801 significantly reduced proliferation and increased apoptosis in human vestibular schwannoma cells.
J Neurosurg. 2022 Sep 9;138(4):962-971.
Bentamapimod 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
BALB/cAJcl-nu/nu mice
Subcutaneous xenograft model
Intraperitoneal injection
40 mg/kg
Once daily for 10 consecutive days
Systemic administration of AS602801 reduced tumor-initiating cancer stem cells in xenograft tumors without affecting mouse health
Oncotarget. 2016 May 10;7(19):27021-32.
Nude mice
Xenograft model of endometriosis
Oral
10 or 30 mg/kg
Once daily for 30 days
To evaluate the effect of AS602801 on regression of endometriotic lesions. Results showed that 30 mg/kg AS602801 caused 29% regression of lesions.
Reprod Sci. 2016 Jan;23(1):11-23.
Nude mice
Human vestibular schwannoma xenograft model
Oral gavage
60 mg/kg
Twice daily for 65 days
AS602801 reduced tumor volume and cell proliferation but did not significantly increase apoptosis.
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