| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| Other Sizes |
| Targets |
UNC0379 targets the lysine methyltransferase SETD8 (KMT5A). It is a substrate-competitive inhibitor that prevents the methylation of histone H4 lysine 20 (H4K20). SETD8 expression is observed in cancers including bladder cancer, chronic myelogenous leukemia, hepatocellular carcinoma, non-small-cell lung carcinoma, prostate cancer, and small-cell lung carcinoma. Inhibition of SETD8 by UNC0379 may prevent cancer progression.
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| ln Vitro |
UNC0379 TFA (1–10 μM, 9 days) prevents the growth of HGSOC cells [2]. In HGSOC cells, UNC0379 TFA (10 μM, 96 hours) can raise the percentage of sub-G1 phase cells [2]. Ten micrograms of UNC0379 TFA administered over a 48-hour period causes myofibroblast dedifferentiation and prevents new fibroblasts from differentiating into myofibroblasts [3].
UNC0379 demonstrates selective inhibition of SETD8 with an IC50 of 7.3 μM. It displays good selectivity over 15 other methyltransferases, with IC50 values over 100 μM for other methyltransferases. H4K20 methylation has been implicated in the regulation of various biological processes including the DNA damage response. Inhibition leads to alterations in chromatin structure and gene expression. |
| ln Vivo |
In rats with bleomycin (BLM)-induced pulmonary fibrosis, UNC0379 TFA (intratracheally given, 1 mg/kg/day, 1 mg/kg/day, days 7, 8, and 9) reduces lung fibrosis [3].
In vivo activity data for UNC0379 are not extensively detailed in the available literature. As an inhibitor of SETD8, which is overexpressed in multiple cancer types, the compound has potential for anticancer activity. The compound is used as a chemical probe to study the biological functions of H4K20 methylation in various cellular contexts. Specific in vivo efficacy data are not reported. |
| Enzyme Assay |
Specific cell-free enzyme/receptor binding assay protocols for UNC0379 involve histone methyltransferase assays. The compound’s IC50 of 7.3 μM for SETD8 is determined using peptide-based methylation assays. Selectivity is confirmed by testing against 15 other methyltransferases, with IC50 values over 100 μM. Substrate-competitive inhibition is confirmed through kinetic analysis.
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| Cell Assay |
Cell Viability Assay [1]
Cell Types: JHOS2, JHOS3, JHOS4, OVCAR3, OVCAHO, OVKATE, KURAMOCHI, TYKnu Tested Concentrations: 1-10 μM Incubation Duration: 9 days Experimental Results: Inhibits HGSOC cell proliferation with IC50 ranging from 0.39 to 3.20 μM. Cell cycle analysis[1] Cell Types: JHOS3, OVCAR3 Tested Concentrations: 10 µM Incubation Duration: 96 hrs (hours) Experimental Results: Cells were captured in sub-G1 phase. In vitro cell-based assays for UNC0379 use cancer cell lines expressing SETD8. Cells are treated with UNC0379, and H4K20 monomethylation levels are assessed by Western blot using specific antibodies. Effects on cell proliferation, DNA damage response, and gene expression are evaluated. The compound’s selectivity is confirmed by assessing its effects on other histone methylation marks. |
| Animal Protocol |
Animal/Disease Models: Bleomycin (BLM)-induced pulmonary fibrosis mouse model [3]
Doses: 1 mg/kg/day Route of Administration: intratubular administration on days 7, 8 and 9. Experimental Results: Improved BLM-induced pulmonary fibrosis (supported by assessment of Ashcroft score and changes in collagen content in lung samples) without affecting lung inflammation. In vivo animal studies for UNC0379 are not detailed in the available literature. As an epigenetic inhibitor targeting SETD8, which is overexpressed in multiple cancers, typical in vivo evaluation would involve xenograft mouse models. Tumor-bearing mice would be treated with UNC0379, and tumor growth inhibition, H4K20 methylation levels, and survival would be monitored. |
| ADME/Pharmacokinetics |
Detailed pharmacokinetic properties of UNC0379 trifluoroacetate salt are not extensively reported. The compound has a molecular formula of C23H35N5O2 · xC2HF3O2 and a molecular weight of 527.58 g/mol. It is soluble in H2O at 5 mg/mL and appears as a white to beige powder. Purity is ≥98% (HPLC). Storage: at 2–8°C, desiccated. The compound has the SMILES string COC1=C(OC)C=C(N=C(N2CCCC2)N=C3NCCCCCN4CCCC4)C3=C1.
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| Toxicity/Toxicokinetics |
Specific toxicological data for UNC0379 are not detailed in the available literature. The compound is classified for research use only and is not intended for human therapeutic use. As an inhibitor of histone methylation, potential toxicities would relate to epigenetic effects on gene expression, though formal toxicological profiles are not reported.
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| References |
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| Additional Infomation |
UNC0379 trifluoroacetate salt (CAS 1620401-83-3) is the first substrate-competitive inhibitor of the lysine methyltransferase SETD8, the only known methyltransferase that catalyzes monomethylation of histone H4 lysine 20 (H4K20). It has an IC50 of 7.3 μM for SETD8 and displays good selectivity over 15 other methyltransferases. SETD8 expression is observed in multiple cancers. No clinical trial or approved indication data are available.
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| Molecular Formula |
C25H36F3N5O4
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|---|---|
| Molecular Weight |
527.5797
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| Exact Mass |
527.271
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| CAS # |
1620401-83-3
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| Related CAS # |
UNC0379;1620401-82-2
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| PubChem CID |
92044361
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| Appearance |
Light yellow to khaki solid powder
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
12
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
37
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| Complexity |
581
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| Defined Atom Stereocenter Count |
0
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| SMILES |
COC1=C(C=C2C(=C1)C(=NC(=N2)N3CCCC3)NCCCCCN4CCCC4)OC.C(=O)(C(F)(F)F)O
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| InChi Key |
NRGGPYZTHNAVFM-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H35N5O2.C2HF3O2/c1-29-20-16-18-19(17-21(20)30-2)25-23(28-14-8-9-15-28)26-22(18)24-10-4-3-5-11-27-12-6-7-13-27;3-2(4,5)1(6)7/h16-17H,3-15H2,1-2H3,(H,24,25,26);(H,6,7)
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| Chemical Name |
6,7-dimethoxy-2-pyrrolidin-1-yl-N-(5-pyrrolidin-1-ylpentyl)quinazolin-4-amine;2,2,2-trifluoroacetic acid
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
H2O : ~100 mg/mL (~189.54 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8954 mL | 9.4772 mL | 18.9545 mL | |
| 5 mM | 0.3791 mL | 1.8954 mL | 3.7909 mL | |
| 10 mM | 0.1895 mL | 0.9477 mL | 1.8954 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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