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Chemical Structure| 1255580-76-7 Chemical Structure| 1255580-76-7

Structure of UNC0638
CAS No.: 1255580-76-7

Chemical Structure| 1255580-76-7

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UNC0638 is an inhibitor of protein lysine methyltransferases G9a and GLP with IC50 of < 15 nM, 19 nM, respectively.

4.5 *For Research Use Only! Not for Human Use. We Do Not Sell to Patients.

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Product Citations

Product Citations

Wang, Jianfeng ; Yin, Xiaomao ; He, Wei ; Xue, Wei ; Zhang, Jin ; Huang, Yiran

Abstract: Clear cell renal cell carcinoma (ccRCC) is a common kidney malignancy characterized by a poor prognosis. Suppressor of variegation 3–9 homolog 1 (SUV39H1), which encodes a histone H3 lysine 9 methyltransferase, has been reported to act as an oncogene in many cancers. However, it is unclear whether SUV39H1 is involved in ccRCC. Here, we report that SUV39H1 expression is frequently upregulated in ccRCC tumors and is significantly correlated with ccRCC progression. SUV39H1 expression level is an independent risk factor for cancer prognosis, and integration with several known prognostic factors predicted ccRCC patient prognosis with improved accuracy than the conventional SSIGN (stage, size, grade and necrosis) prognostic model. Mechanistically, we discovered that siRNA knockdown or pharmacological inhibition of SUV39H1 induced iron accumulation and lipid peroxidation, leading to ferroptosis that disrupted ccRCC cell growth in vitro and in vivo. We also show that SUV39H1 deficiency modulated the H3K9me3 status of the DPP4 (dipeptidyl-peptidase-4) gene promoter, resulting in upregulation of its expression that contributes to ferroptosis. Taken together, our findings provide the mechanistic insight into SUV39H1-dependent epigenetic control of ccRCC tumor growth and indicate that SUV39H1 may serve as a potential therapeutic target for ccRCC treatment.

Keywords: Clear cell renal cell carcinoma ; SUV39H1 ; Progression ; Prognostic model ; Ferroptosis ; DPP4 ; Epigenetics ; Therapeutic target

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Product Details of UNC0638

CAS No. :1255580-76-7
Formula : C30H47N5O2
M.W : 509.73
SMILES Code : COC1=CC2=C(NC3CCN(C(C)C)CC3)N=C(C4CCCCC4)N=C2C=C1OCCCN5CCCC5
English Name :2-Cyclohexyl-N-(1-isopropylpiperidin-4-yl)-6-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)quinazolin-4-amine
MDL No. :MFCD22208587
InChI Key :QOECJCJVIMVJGX-UHFFFAOYSA-N
Pubchem ID :46224516

Safety of UNC0638

Related Pathways of UNC0638

epigenetics

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
MCF7 cells 320 nM 14 days To study the regulatory effect of UNC0638 on H3K9me2 levels, results showed that UNC0638 significantly reduced genomic regions containing H3K9me2. Nat Chem Biol. 2011 Jul 10;7(8):566-74.
HL-60 cells 50 µM 24 hours High concentration of UNC0638 induced cell death in AML cells Blood Cancer J. 2015 May 15;5(5):e313.
KG-1a cells 50 µM 24 hours High concentration of UNC0638 induced cell death in AML cells Blood Cancer J. 2015 May 15;5(5):e313.
U937 cells 50 µM 24 hours High concentration of UNC0638 induced cell death in AML cells Blood Cancer J. 2015 May 15;5(5):e313.
U2OS cells 3 µM 24 hours UNC0638 dramatically inhibited the retention of BRCA1 and BARD1 at DNA damage sites, but did not affect the retention of 53BP1, RNF168, or RAP80. Cancer Res. 2015 Apr 1;75(7):1311-21.
Mouse Embryonic Fibroblasts (MEFs) 1.6 µM 3 days UNC0638 activated the expression of maternal Snrpn-EGFP, indicating its inhibitory effect on G9a Nat Med. 2017 Feb;23(2):213-222.
MDA-MB-231 cells 81 ± 9 nM (IC50) 48 hours To evaluate the inhibitory effect of UNC0638 on H3K9me2 levels, results showed that UNC0638 significantly reduced H3K9me2 levels. Nat Chem Biol. 2011 Jul 10;7(8):566-74.
J1 mES cells 138 nM 48 hours To evaluate the inhibitory effect of UNC0638 on H3K9me2 levels, results showed that UNC0638 was more effective than BIX01294. Nat Chem Biol. 2011 Jul 10;7(8):566-74.
Human PWS Fibroblasts 4 µM 72 hours UNC0638 activated the transcription of SNRPN and SNORD116, indicating its inhibitory effect on G9a Nat Med. 2017 Feb;23(2):213-222.
A549 5 µM 72 hours UNC0638 significantly decreased H3K9Me2 protein level and inhibited the proliferation of A549 cells Mol Cancer. 2018 Oct 22;17(1):153.
H1299 2.5 µM 72 hours UNC0638 significantly decreased H3K9Me2 protein level and inhibited the proliferation of H1299 cells Mol Cancer. 2018 Oct 22;17(1):153.
H1975 3.5 µM 72 hours UNC0638 significantly decreased H3K9Me2 protein level and inhibited the proliferation of H1975 cells Mol Cancer. 2018 Oct 22;17(1):153.
YB5 cells 1 µM 96 hours UNC0638 affects 1.4% of the transcriptome, and preferentially targets genes marked with H3K9me2 Cancer Res. 2017 Jan 15;77(2):470-481.
MCF7 cells 1 µM 96 hours UNC0638 affects 1.4% of the transcriptome, and preferentially targets genes marked with H3K9me2 Cancer Res. 2017 Jan 15;77(2):470-481.
HL60 cells 1 µM 96 hours UNC0638 affects 1.4% of the transcriptome, and preferentially targets genes marked with H3K9me2 Cancer Res. 2017 Jan 15;77(2):470-481.

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
NOD/SCID/IL2Rgamma null mice (NSG) H1299 xenograft model Intraperitoneal injection 10 mg/kg Once daily for 14 days UNC0638 significantly inhibited the growth of H1299 xenograft tumors and suppressed Wnt signaling pathway activity Mol Cancer. 2018 Oct 22;17(1):153.
Mice M+/pΔS−U mouse model Intraperitoneal injection 2.5 mg/kg Once daily for 5 days UNC0642 significantly improved the survival and growth of m+/pΔS?U mice Nat Med. 2017 Feb;23(2):213-222.

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.96mL

0.39mL

0.20mL

9.81mL

1.96mL

0.98mL

19.62mL

3.92mL

1.96mL

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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