WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H406564
CAS#: 1620401-82-2 (free base)
Description: UNC0379 is a selective, substrate-competitive inhibitor of the lysine methyltransferase SETD8. UNC0379 is active in multiple biochemical assays. Its affinity to SETD8 was confirmed by ITC (isothermal titration calorimetry) and SPR (surface plasmon resonance) studies. Importantly, UNC0379 is selective for SETD8 over 15 other methyltransferases. The lysine methyltransferase SETD8 is the only known methyltransferase that catalyzes monomethylation of histone H4 lysine 20 (H4K20). Monomethylation of H4K20 has been implicated in regulating diverse biological processes including the DNA damage response.
Hodoodo Cat#: H406564
Name: UNC0379
CAS#: 1620401-82-2 (free base)
Chemical Formula: C23H35N5O2
Exact Mass: 413.28
Molecular Weight: 413.556
Elemental Analysis: C, 66.80; H, 8.53; N, 16.93; O, 7.74
Related CAS #: 1620401-83-3 (trifluoroacetate) 1620401-82-2 (free base)
Synonym: UNC0379, UNC-0379, UNC 0379
IUPAC/Chemical Name: 6,7-dimethoxy-2-(pyrrolidin-1-yl)-N-(5-(pyrrolidin-1-yl)pentyl)quinazolin-4-amine
InChi Key: WEXCGGWTIDNVNT-UHFFFAOYSA-N
InChi Code: InChI=1S/C23H35N5O2/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/h16-17H,3-15H2,1-2H3,(H,24,25,26)
SMILES Code: COC1=C(OC)C=C(N=C(N2CCCC2)N=C3NCCCCCN4CCCC4)C3=C1
Appearance: Off-white to light beige solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info:
| Biological target: | UNC0379 is a selective, substrate-competitive inhibitor of lysine methyltransferase SETD8 (KMT5A) with an IC50 of 7.3 μM. |
| In vitro activity: | Application of UNC0379 to the IPF-MyoF resulted in a spindle-shaped morphology accompanied by a decrease in the expression of both α-SMA and ED-A-FN. These findings were supported by the results of the flowcytometric analysis (Supplementary Figure S3). α-SMA+ED-A-FN+ IPF-MyoF had high SSC that could be proportional to intracellular organelle complexity, which was significantly reduced by the treatment of IPF-MyoF with UNC0379. In conjunction with this phenomenon, the SSClowFSClow cell population mostly comprised of α-SMA–ED-A-FN– and α-SMAlowED-A-FN– fractions were negligible in the IPF-MyoF but significantly increased in response to the treatment with UNC0379. Along with the WB analysis, these results suggest that UNC0379 can induce the dedifferentiation of IPF-MyoF based on specific marker expression and morphology. Reference: Front Mol Biosci. 2020; 7: 192. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7419601/ |
| In vivo activity: | This study evaluated effects of SETD8 inhibition on in vivo tumor growth. Bioavailability and animal toxicology precluded treatment of mice with the SETD8 inhibitor UNC0379 (Ma et al., 2014a). The study therefore performed an ex-vivo tumorigenicity assay by exposing NB (neuroblastoma) cells to 2 μM UNC0379 or control solvent for 24 hr in vitro, then subcutaneously implanting treated NB cells into nude mice and monitoring tumor growth. Pharmacological inhibition of SETD8 showed decreased NB tumor growth in vivo and significantly reduced SY5Y (p ≤ 0.01) and NGP (p = 0.026) tumor growth (Figure 7A). Assessment of tumor lysates indicated that UNC0379 treatment reduced levels of p53K382me1 modification in xenografts (Figure 7A, insets). Kaplan-Meier survival curves revealed a statistically significant survival advantage for mice bearing ex-vivo UNC0379-treated NGP or SY5Y NB cells compared with control-treated NB cells (Figure 7B). These results suggest that a small molecule inhibitor of SETD8 may have therapeutic relevance. Reference: Cancer Cell. 2017 Jan 9; 31(1): 50–63. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5233415/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 50.7 | 122.52 | |
| DMSO:PBS (pH 7.2) (1:1) | 0.5 | 1.21 | |
| DMF | 20.0 | 48.36 | |
| Ethanol | 10.0 | 24.18 |
The following data is based on the product molecular weight 413.56 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Ugai K, Matsuda S, Mikami H, Shimada A, Misawa T, Nakamura H, Tatsumi K, Hatano M, Murayama T, Kasuya Y. Inhibition of the SET8 Pathway Ameliorates Lung Fibrosis Even Through Fibroblast Dedifferentiation. Front Mol Biosci. 2020 Aug 5;7:192. doi: 10.3389/fmolb.2020.00192. PMID: 32850975; PMCID: PMC7419601. 2. Ma A, Yu W, Li F, Bleich RM, Herold JM, Butler KV, Norris JL, Korboukh V, Tripathy A, Janzen WP, Arrowsmith CH, Frye SV, Vedadi M, Brown PJ, Jin J. Discovery of a selective, substrate-competitive inhibitor of the lysine methyltransferase SETD8. J Med Chem. 2014 Aug 14;57(15):6822-33. doi: 10.1021/jm500871s. Epub 2014 Jul 25. PMID: 25032507; PMCID: PMC4136711. 3. Wu J, Qiao K, Du Y, Zhang X, Cheng H, Peng L, Guo Z. Downregulation of histone methyltransferase SET8 inhibits progression of hepatocellular carcinoma. Sci Rep. 2020 Mar 11;10(1):4490. doi: 10.1038/s41598-020-61402-7. PMID: 32161353; PMCID: PMC7066161. 4. Veschi V, Liu Z, Voss TC, Ozbun L, Gryder B, Yan C, Hu Y, Ma A, Jin J, Mazur SJ, Lam N, Souza BK, Giannini G, Hager GL, Arrowsmith CH, Khan J, Appella E, Thiele CJ. Epigenetic siRNA and Chemical Screens Identify SETD8 Inhibition as a Therapeutic Strategy for p53 Activation in High-Risk Neuroblastoma. Cancer Cell. 2017 Jan 9;31(1):50-63. doi: 10.1016/j.ccell.2016.12.002. PMID: 28073004; PMCID: PMC5233415. |
| In vitro protocol: | 1. Ugai K, Matsuda S, Mikami H, Shimada A, Misawa T, Nakamura H, Tatsumi K, Hatano M, Murayama T, Kasuya Y. Inhibition of the SET8 Pathway Ameliorates Lung Fibrosis Even Through Fibroblast Dedifferentiation. Front Mol Biosci. 2020 Aug 5;7:192. doi: 10.3389/fmolb.2020.00192. PMID: 32850975; PMCID: PMC7419601. 2. Ma A, Yu W, Li F, Bleich RM, Herold JM, Butler KV, Norris JL, Korboukh V, Tripathy A, Janzen WP, Arrowsmith CH, Frye SV, Vedadi M, Brown PJ, Jin J. Discovery of a selective, substrate-competitive inhibitor of the lysine methyltransferase SETD8. J Med Chem. 2014 Aug 14;57(15):6822-33. doi: 10.1021/jm500871s. Epub 2014 Jul 25. PMID: 25032507; PMCID: PMC4136711. |
| In vivo protocol: | 1. Wu J, Qiao K, Du Y, Zhang X, Cheng H, Peng L, Guo Z. Downregulation of histone methyltransferase SET8 inhibits progression of hepatocellular carcinoma. Sci Rep. 2020 Mar 11;10(1):4490. doi: 10.1038/s41598-020-61402-7. PMID: 32161353; PMCID: PMC7066161. 2. Veschi V, Liu Z, Voss TC, Ozbun L, Gryder B, Yan C, Hu Y, Ma A, Jin J, Mazur SJ, Lam N, Souza BK, Giannini G, Hager GL, Arrowsmith CH, Khan J, Appella E, Thiele CJ. Epigenetic siRNA and Chemical Screens Identify SETD8 Inhibition as a Therapeutic Strategy for p53 Activation in High-Risk Neuroblastoma. Cancer Cell. 2017 Jan 9;31(1):50-63. doi: 10.1016/j.ccell.2016.12.002. PMID: 28073004; PMCID: PMC5233415. |
1: Ma A, Yu W, Li F, Bleich RM, Herold JM, Butler KV, Norris JL, Korboukh V, Tripathy A, Janzen WP, Arrowsmith CH, Frye SV, Vedadi M, Brown PJ, Jin J. Discovery of a Selective, Substrate-Competitive Inhibitor of the Lysine Methyltransferase SETD8. J Med Chem. 2014 Aug 14;57(15):6822-33. doi: 10.1021/jm500871s. Epub 2014 Jul 25. PubMed PMID: 25032507; PubMed Central PMCID: PMC4136711.
