UNC0642 is the first G9a and GLP in vivo chemical probe with Ki value of 3.7nM, and displayed high in vitro potency for GLP with IC50<2.5nM. UNC0642 potently inhibited cellular inhibition of H3K9me2 with IC50 values of 110, 130, 130 and 40nM in MDA-MB-231, U2OS, PC3 and PANC-1 cell lines. UNC0642 reduced clonogenicity in PANC-1 cells in a concentration-dependent manner, at concentration of 0.5μM and 1μM, post 2 weeks, while it had no effect on clonogenicity in MDA-MB-231 cells[4]. UNC0642 caused a selective reduction of the dimethylation of histone H3 lysine 9 (H3K9me2) at PWS-IC (Prader–Willi syndrome), without changing DNA methylation, and activated candidate PWS-associated genes. UNC0642 improved survival and growth in a mouse model with a paternal deletion from Snrpn to Ube3a (m+/p∆S−U)[5].
作用机制
UNC0642 is competitive with the substrate and non-competitive with the cofactor SAM.[4]
UNC0642 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Hep3B cells
1.0 µM
24 hours
UNC0642 significantly inhibited the proliferation of Hep3B cells, with a significant reduction in the percentage of Ki67-positive cells.
Cell Biosci. 2021 Aug 3;11(1):152.
Huh1 cells
1.0 µM
24 hours
UNC0642 significantly inhibited the proliferation of Huh1 cells, with a significant reduction in the percentage of Ki67-positive cells.
Cell Biosci. 2021 Aug 3;11(1):152.
T24 cells
9.85 ± 0.41 µM
72 hours
UNC0642 significantly reduced T24 cell viability and induced apoptosis
Acta Pharmacol Sin. 2019 Aug;40(8):1076-1084.
J82 cells
13.15 ± 1.72 µM
72 hours
UNC0642 significantly reduced J82 cell viability and induced apoptosis
Acta Pharmacol Sin. 2019 Aug;40(8):1076-1084.
5637 cells
9.57 ± 0.37 µM
72 hours
UNC0642 significantly reduced 5637 cell viability and induced apoptosis
Acta Pharmacol Sin. 2019 Aug;40(8):1076-1084.
FSC
1.0 µM
96 hours
The experiment aimed to assess the effect of the G9a inhibitor UNC0642 on restoring the loss of cholinergic neuron markers caused by ethanol exposure.
Mol Psychiatry. 2023 Dec;28(12):5159-5172.
UNC0642 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
M+/pαS−U
Intraperitoneal injection
2.5 mg/kg
Daily for 5 days starting at P7
Therapeutic effects enhancing survival and growth
Nat Med. 2017 Feb;23(2):213-222.
Mice
NICD/Akt-injected mice
Intraperitoneal injection
2.5 mg/kg
Every other day for 3 weeks
UNC0642 treatment inhibited tumor growth in this model of cholangiocarcinogenesis.
Hepatology. 2020 Oct;72(4):1283-1297
Nude mice
Hep3B and Huh1 xenograft model
Intraperitoneal injection
5 mg/kg
Every 3 days for 1 month
UNC0642 significantly inhibited tumor growth in Hep3B and Huh1 cells, with a significant reduction in final tumor weight.
Cell Biosci. 2021 Aug 3;11(1):152.
Nude mice
J82 xenograft model
Intraperitoneal injection
5 mg/kg
Every other day for 11 days
UNC0642 significantly suppressed tumor growth and induced apoptosis
Acta Pharmacol Sin. 2019 Aug;40(8):1076-1084.
Rats
AIE model
Intragastric
5.0 g/kg
2 days on/2 days off for approximately 4 weeks
To examine the long-term effects of alcohol exposure on cholinergic neurons and assess potential neuroimmune signaling mechanisms.
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