UNC0642

Catalog No.S7230

For research use only.

UNC0642 is a potent, selective inhibitor of histone methyltransferases G9a/GLP with IC50s less than 2.5 nM for G9a and GLP and shows more than 300-fold selective for G9a and GLP over a broad range of kinases, GPCRs, transporters, and ion channels.

UNC0642 Chemical Structure

CAS No. 1481677-78-4

Selleck's UNC0642 has been cited by 7 Publications

Purity & Quality Control

Choose Selective Histone Methyltransferase Inhibitors

Biological Activity

Description UNC0642 is a potent, selective inhibitor of histone methyltransferases G9a/GLP with IC50s less than 2.5 nM for G9a and GLP and shows more than 300-fold selective for G9a and GLP over a broad range of kinases, GPCRs, transporters, and ion channels.
Targets
G9a [1]
(Cell-free assay)
GLP [1]
(Cell-free assay)
<2.5 nM <2.5 nM
In vitro

UNC0642 is competitive with the peptide substrate and non-competitive with the cofactor SAM. The Ki of UNC0642 is determined to be 3.7 ± 1 nM. It is more than 20,000-fold selective for G9a and GLP over 13 other methyltransferases (IC50 > 50,000 nM) and more than 2,000-fold selective over PRC2-EZH2 (IC50 > 5,000 nM). UNC0642 displays high potency (IC50 < 150 nM) in reducing cellular levels of H3K9me2, low cell toxicity (EC50 > 3,000 nM), resulting in a good separation of functional potency and cell toxicity with a tox/function ratio (which is determined by dividing the EC50 value of the observed toxicity by the IC50 value of the functional potency) of > 45 in U2OS, PC3, and PANC-1 cells. UNC0642 reduces clonogenicity in PANC-1 cells in a concentration-dependent manner while it has no effect on clonogenicity in MDA-MB-231 cells[1].

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
PANC1 NXPpTGNNTnWwY4Tpc44h[XO|YYm= M3m2UGlvcGmkaYTpc44hd2ZibInzbY5mKG2ndHj5cJRz[W6|ZnXyZZNmKEd7YTDpckBpfW2jbjDQRW5EOSClZXzsd{Bie3Onc4Pl[EBieyC{ZXT1Z5Rqd25ib3[gTFNMQW2nMjDj[YxtfWyjcjDs[ZZmdCCkeTDpcY12dm:obIXvdoV{[2WwY3WgbY4u[2WubDDX[ZN1\XKwIHHzd4F6NCCLQ{WwJF0hOC5yNDFOwG0v M1voVlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MUCyNVM1Lz5{NEGwNlE{PDxxYU6=
MDA-MB-231 MXjGeY5kfGmxbjDhd5NigQ>? NV7ZVmxCUW6qaXLpeIlwdiCxZjDsfZNqdmVibXX0bJltfHKjboPm[ZJie2ViR{nhJIlvKGi3bXHuJG1FSS2PQj2yN|Eh[2WubIOgZZN{\XO|ZXSgZZMhemWmdXP0bY9vKG:oIFizT|lu\TJiY3XscJVt[XJibHX2[Ywh[nliaX3teY5w\my3b4Lld4NmdmOnIHnuMYNmdGxiV3XzeIVzdiCjc4PhfUwhUUN3MDC9JFAvOTFizszNMi=> MXO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDFyMkGzOEc,OjRzMEKxN|Q9N2F-
PC3 NITnbYJHfW6ldHnvckBie3OjeR?= NYrRPJdtUW6qaXLpeIlwdiCxZjDsfZNqdmVibXX0bJltfHKjboPm[ZJie2ViR{nhJIlvKGi3bXHuJHBEOyClZXzsd{Bie3Onc4Pl[EBieyC{ZXT1Z5Rqd25ib3[gTFNMQW2nMjDj[YxtfWyjcjDs[ZZmdCCkeTDpcY12dm:obIXvdoV{[2WwY3WgbY4u[2WubDDX[ZN1\XKwIHHzd4F6NCCLQ{WwJF0hOC5zMzFOwG0v MnznQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRzMEKxN|QoRjJ2MUCyNVM1RC:jPh?=
U2OS MX;GeY5kfGmxbjDhd5NigQ>? MoDCTY5pcWKrdHnvckBw\iCueYPpcoUhdWW2aInseJJidnOoZYLhd4UhTzmjIHnuJIh2dWGwIGWyU3Mh[2WubIOgZZN{\XO|ZXSgZZMhemWmdXP0bY9vKG:oIFizT|lu\TJiY3XscJVt[XJibHX2[Ywh[nliaX3teY5w\my3b4Lld4NmdmOnIHnuMYNmdGxiV3XzeIVzdiCjc4PhfUwhUUN3MDC9JFAvOTNizszNMi=> MVq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDFyMkGzOEc,OjRzMEKxN|Q9N2F-
PANC1 NH6weplEgXSxdH;4bYNqfHliYYPzZZk> M17CTFQ5KGi{cx?= MUHDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDQRW5EOSClZXzsd{Bi\nSncjC0PEBpenNiYomgRYxidWG{IFLseYUh[XO|YYmsJGVEPTBiPTCzMlUh|ryPLh?= NXPOTJZYRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSxNFIyOzRpPkK0NVAzOTN2PD;hQi=>
U2OS NHXEUIVEgXSxdH;4bYNqfHliYYPzZZk> MUi0PEBpenN? M2XqWGN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJHUzV1NiY3XscJMh[W[2ZYKgOFghcHK|IHL5JGFt[W2jcjDCcJVmKGG|c3H5MEBGSzVyIE2gOkDPxE1w MX:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDFyMkGzOEc,OjRzMEKxN|Q9N2F-
PC3 M3;WO2N6fG:2b4jpZ4l1gSCjc4PhfS=> M4jSXVQ5KGi{cx?= NUHCWZRXS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hWEN|IHPlcIx{KGGodHXyJFQ5KGi{czDifUBCdGGvYYKgRox2\SCjc4PhfUwhTUN3MDC9JFgvQSEQvF2u MkLzQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRzMEKxN|QoRjJ2MUCyNVM1RC:jPh?=
MDA-MB-231 MmKxR5l1d3SxeHnjbZR6KGG|c3H5 NIDRc4o1QCCqcoO= MkDTR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gUWRCNU2ELUKzNUBk\WyuczDh[pRmeiB2ODDodpMh[nliQXzhcYFzKEKudXWgZZN{[XluIFXDOVAhRSBzNj63JO69VS5? NY\CSndiRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSxNFIyOzRpPkK0NVAzOTN2PD;hQi=>
Assay
Methods Test Index PMID
Growth inhibition assay Cell viability 28630300
Western blot G9A / di-mH3K9 / ERBB3 31619200
In vivo For evaluation in vivo PK properties in male Swiss Albino mice, a single intraperitoneal (IP) injection (5 mg/kg) of UNC0642 results in a plasma Cmax (maximum concentration) of 947 ng/mL and an AUC (area under the curve) of 1265 hr*ng/mL. It displays modest brain penetration with a brain/plasma ratio of 0.33[1]. A single intraperitoneal (i.p.) injection dose of 5 mg/kg of UNC0642 is sufficient to inhibit G9a activity in adult mice. UNC0642 improves the life span and weight gain of m+/pΔS−U pups, produces long-lasting activation of PWS-associated genes, is apparently well tolerated and produces no notable acute toxicity, and does not interfere with the expression of the AS-associated Ube3a gene[2].

Protocol (from reference)

Cell Research:

[1]

  • Cell lines: MDA-MB-231, PC3, and U2OS cells
  • Concentrations: --
  • Incubation Time: 48 h
  • Method:

    MDA-MB-231, PC3, and U2OS cells are cultured in RPMI with 10% FBS, PANC-1 cells in DMEM with 10% FBS. Cells are treated with inhibitors for 48 h. Cell viability assays are performed by incubating cells with 0.1 mg/mL of resazurin for 3-4 h. Resazurin reduction is monitored with 544 nm excitation, measuring fluorescence at 590 nm.

Animal Research:

[1]

  • Animal Models: male Swiss Albino mice
  • Dosages: 5 mg/kg
  • Administration: i.p.

Solubility (25°C)

In vitro

DMSO 100 mg/mL
(182.91 mM)
Ethanol 100 mg/mL
(182.91 mM)
Water Insoluble

Chemical Information

Molecular Weight 546.7
Formula

C29H44F2N6O2

CAS No. 1481677-78-4
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CC(C)N1CCC(CC1)NC2=NC(=NC3=CC(=C(C=C32)OC)OCCCN4CCCC4)N5CCC(CC5)(F)F

In vivo Formulation Calculator (Clear solution)

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Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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Molarity Calculator

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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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