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Chemical Structure| 1620401-82-2 Chemical Structure| 1620401-82-2

Structure of UNC0379
CAS No.: 1620401-82-2

Chemical Structure| 1620401-82-2

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UNC0379 is a selective inhibitor of the lysine methyltransferase SETD8 with IC50 of 7.3 ± 1.0 μM.

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Product Details of UNC0379

CAS No. :1620401-82-2
Formula : C23H35N5O2
M.W : 413.56
SMILES Code : COC1=CC2=NC(N3CCCC3)=NC(NCCCCCN4CCCC4)=C2C=C1OC
MDL No. :MFCD28167817
InChI Key :WEXCGGWTIDNVNT-UHFFFAOYSA-N
Pubchem ID :78357767

Safety of UNC0379

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of UNC0379

epigenetics

Isoform Comparison

Biological Activity

Target
  • Histone Methyltransferase

    SETD8, IC50:7.9 μM

In Vitro:

Cell Line
Concentration Treated Time Description References
Mouse 5T33MMvv cells 2.5 µM to 40 µM 24 hours Evaluate the toxic effects of UNC-0379 on murine MM cell models, showing a significant reduction in cell viability. Clin Epigenetics. 2021 Sep 16;13(1):174.
Primary MM cells 1 µM, 2.5 µM, 5 µM 4 days Assess the toxic effects of UNC-0379 on primary MM cells, demonstrating a significant reduction in malignant plasma cell numbers. Clin Epigenetics. 2021 Sep 16;13(1):174.
Human myeloma cell lines (HMCLs) 1 µM, 2.5 µM, 5 µM 4 days Evaluate the toxic effects of UNC-0379 on HMCLs, showing dose-dependent inhibition of cell growth. Clin Epigenetics. 2021 Sep 16;13(1):174.
NHLF 10 µM 48 hours UNC0379 was sensitive to the upregulation of ED-A-FN in NHLF, suggesting that SET8 may be involved in TGF-β1-induced FMD in normal fibroblasts. Front Mol Biosci. 2020 Aug 5;7:192.
IPF-MyoF 10 µM 48 hours UNC0379 significantly suppressed the expression of α-SMA and ED-A-FN, reversing the phenotype of IPF-MyoF. Front Mol Biosci. 2020 Aug 5;7:192.
TYK-nu 10 µM 72 hours Inhibition of cell proliferation and induction of apoptosis Biomolecules. 2020 Dec 16;10(12):1686.
OVCAR3 10 µM 96 hours Inhibition of cell proliferation and induction of apoptosis Biomolecules. 2020 Dec 16;10(12):1686.
JHOS3 10 µM 96 hours Inhibition of cell proliferation and induction of apoptosis Biomolecules. 2020 Dec 16;10(12):1686.
MDA-MB-231 cells 5 or 10 µM 48 hours To verify the inhibitory effect of UNC0379 on the proliferation of breast cancer cells, the results showed that as the concentration of UNC0379 increased, the proliferation of MDA-MB-231 cells was more strongly inhibited. Oncol Rep. 2024 Aug;52(2):110.
CR-CSphCs 0.5, 1, 2, 4, 8 µg/ml 48 hours Evaluating the effect of UNC0379 on CR-CSphCs, results showed that UNC0379 treatment led to a gradual decrease in p53K382me1 and H4K20me1 protein levels while restoring p53 and p21 levels and reducing colony-forming capability. Mol Cancer. 2025 Mar 31;24(1):102.
THP1 cells 0.5, 1, 2, 4, 8 µg/ml 48 hours Evaluating the effect of UNC0379 on THP1 cells, results showed that UNC0379 treatment led to a gradual decrease in p53K382me1 and H4K20me1 protein levels while restoring p53 and p21 levels. Mol Cancer. 2025 Mar 31;24(1):102.
BMSC cells 2 µM 48 hours Evaluate the cytotoxicity of UNC0379 on BMSC cells, results showed BMSC cells were not sensitive to UNC0379. Cell Death Dis. 2024 Jul 10;15(7):494.
SK-NEP-1 cells 2 µM 48 hours Evaluate the cytotoxicity of UNC0379 on SK-NEP-1 cells, results showed SK-NEP-1 cells were sensitive to UNC0379. Cell Death Dis. 2024 Jul 10;15(7):494.
SKNMC cells 2 µM 48 hours Evaluate the cytotoxicity of UNC0379 on SKNMC cells, results showed SKNMC cells were sensitive to UNC0379. Cell Death Dis. 2024 Jul 10;15(7):494.
Glioblastoma primary cells 5 µM 48 hours SETD8 inhibition resulted in p53 protein stabilization and p21 accumulation Cell Death Dis. 2023 Sep 27;14(9):638.
SW1088 cells 5 µM 48 hours SETD8 inhibition resulted in increased DNA damage, Chk1 phosphorylation, and G2/M arrest Cell Death Dis. 2023 Sep 27;14(9):638.
U251 cells 5 µM 48 hours SETD8 inhibition resulted in increased DNA damage, Chk1 phosphorylation, and G2/M arrest Cell Death Dis. 2023 Sep 27;14(9):638.
LN-18 cells 5 µM 48 hours SETD8 inhibition resulted in increased DNA damage, p53 protein stabilization, p21 accumulation, and G1/S arrest Cell Death Dis. 2023 Sep 27;14(9):638.
U87MG cells 5 µM 48 hours SETD8 inhibition resulted in increased DNA damage, p53 protein stabilization, p21 accumulation, and G1/S arrest Cell Death Dis. 2023 Sep 27;14(9):638.
CaSki cells 9.97 ± 0.58 µM (IC50) 48 hours UNC0379 enhanced the sensitivity of CaSki cells to cisplatin, reducing the IC50 value. Cell Biosci. 2023 Jun 12;13(1):107.
SiHa cells 8.73 ± 0.49 µM (IC50) 48 hours UNC0379 enhanced the sensitivity of SiHa cells to cisplatin, reducing the IC50 value. Cell Biosci. 2023 Jun 12;13(1):107.
SK-N-BE2C (MYCN-amp) 0.1-30 µM 7 days UNC0379 exhibited antitumor activity in MYCN-amplified NB cell lines with IC50 values ranging from 0.64 to 7 μM. Cancer Cell. 2017 Jan 9;31(1):50-63.
SY5Y (MYCN-WT) 0.1-30 µM 7 days UNC0379, a selective, substrate-competitive inhibitor of SETD8, was one of the most active compounds, exhibiting a relatively low average IC50 (2 μM) and a highly significant p value for the In Vitro Therapeutic Index (IVTI) across the 8 NB cell lines compared with control cell lines. Cancer Cell. 2017 Jan 9;31(1):50-63.
Huh-7 cells 5 µM and 10 µM 72 hours UNC0379 significantly inhibited the proliferation, migration, and invasion of Huh-7 cells. Sci Rep. 2020 Mar 11;10(1):4490.
SMMC-7721 cells 5 µM and 10 µM 72 hours UNC0379 significantly inhibited the proliferation, migration, and invasion of SMMC-7721 cells. Sci Rep. 2020 Mar 11;10(1):4490.
RDES cells 2 µM 72 hours Evaluate the cytotoxicity of UNC0379 on RDES cells, results showed RDES cells were sensitive to UNC0379. Cell Death Dis. 2024 Jul 10;15(7):494.
A673 cells 2 µM 72 hours Evaluate the cytotoxicity of UNC0379 on A673 cells, results showed A673 cells were sensitive to UNC0379. Cell Death Dis. 2024 Jul 10;15(7):494.

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
C57BL/6J mice BLM-induced lung fibrosis model Intratracheal administration 1 mg/kg/day Administered at 7, 8, and 9 dpi UNC0379 significantly ameliorated BLM-induced lung fibrosis without affecting inflammatory responses. Front Mol Biosci. 2020 Aug 5;7:192.
Nude mice Neuroblastoma xenograft model Ex-vivo treatment followed by subcutaneous implantation 2 μM Single treatment for 24 hours followed by implantation and tumor growth monitoring UNC0379 treatment significantly inhibited tumor growth of SY5Y and NGP neuroblastoma cells in vivo and significantly prolonged murine survival. Cancer Cell. 2017 Jan 9;31(1):50-63.
Nude mice A673 cell xenograft model 30 mg/kg/day Once daily for 14 days Evaluate the anti-tumor effect of UNC0379 in vivo, results showed UNC0379 significantly reduced tumor volume and weight. Cell Death Dis. 2024 Jul 10;15(7):494.
NSG mice Subcutaneous and intrasplenic injection models Intraperitoneal injection 5 mg/kg 3 times per week for 3 weeks Evaluating the effect of UNC0379 on tumor growth and metastasis in vivo, results showed that UNC0379 alone or in combination with Tocilizumab delayed disease progression and prolonged survival. Mol Cancer. 2025 Mar 31;24(1):102.
C57BL/6J mice Cisplatin-induced acute kidney injury (AKI) model Intraperitoneal injection 5 mg/kg Once daily for three consecutive days To investigate the effect of UNC0379 on cisplatin-induced AKI, results showed that UNC0379 improved renal function, attenuated renal tubular damage, and restored PTEN expression. Cell Death Dis. 2025 Mar 31;16(1):226.
BALB/c nude mice Subcutaneous tumor model Intraperitoneal and subcutaneous injection 5 mg/kg Twice weekly cisplatin and thrice weekly UNC0379 for 18 days UNC0379 significantly reduced tumor size and weight, enhancing the therapeutic effect of cisplatin. Cell Biosci. 2023 Jun 12;13(1):107.
CD1 mice Glioblastoma xenograft model 5 μM UNC0379 + 400 nM adavosertib From day 8 to day 21 UNC0379 and adavosertib combination significantly inhibited glioblastoma growth Cell Death Dis. 2023 Sep 27;14(9):638.

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.42mL

0.48mL

0.24mL

12.09mL

2.42mL

1.21mL

24.18mL

4.84mL

2.42mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

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