SKI-73

SKI-73 A chemical probe for PRMT4

  • overview
  • properties
  • co-crystal structures
overview
Probe Negative control

 

SKI-73

 

SKI-73N

The SGC in collaboration with the Memorial Sloan Kettering Cancer Center has developed SKI-73, a chemical probe for PRMT4.  SKI-73 is active in cells and is the prodrug of SKI-72, a potent and selective inhibitor of PRMT4.

Data relating to the discovery of this probe is being prepared for publication.  In the meantime, in order to facilitate research by the community we are making this compound available through this website

properties
Probe Negative control

 

SKI-73

 

SKI-73N

Physical and chemical properties for SKI-73
Molecular weight850.4
Molecular formulaC46H58N8O8
IUPAC name2-(3-(5-(5-(5-amino-2,4,7,9-tetraaza-bicyclo[4.3.0]nona-1(6),2,4,7-tetraen-9-yl)-3,4-dihydroxy-tetrahydro-furan-2-yl)-1-((2-(4-methoxy-phenyl)-ethylamino)-formyl)-4-((phenyl-methylamino)-methyl)-pentylamino)-1,1-dimethyl-3-oxo-propyl)-3,5,6-trimethyl-cyclohexa-2,5-diene-1,4-dione
MollogP3.724
PSA186.5
No. of chiral centres6
No. of rotatable bonds21
No. of hydrogen bond acceptors16
No. of hydrogen bond donors7
Physical and chemical properties for SKI-73N (Negative Control)
Molecular weight836.4
Molecular formulaC45H56N8O8
IUPAC name2-(3-(5-(5-(5-amino-2,4,7,9-tetraaza-bicyclo[4.3.0]nona-1(6),2,4,7-tetraen-9-yl)-3,4-dihydroxy-tetrahydro-furan-2-yl)-1-((2-(4-methoxy-phenyl)-ethylamino)-formyl)-4-(phenyl-methylamino)-pentylamino)-1,1-dimethyl-3-oxo-propyl)-3,5,6-trimethyl-cyclohexa-2,5-diene-1,4-dione
MollogP3.239
PSA186.2
No. of chiral centres6
No. of rotatable bonds20
No. of hydrogen bond acceptors16
No. of hydrogen bond donors7
  • SMILES:
  • SKI-73: CC1=C(C(C(C(C)(CC(N[C@H](C(NCCC2=CC=C(OC)C=C2)=O)CC[C@H](CNCC3=CC=CC=C3)C[C@@H]4[C@@H](O)[C@@H](O)[C@@H](O4)N5C=NC6=C5N=CN=C6N)=O)C)=C(C1=O)C)=O)C
  • SKI-73N: CC1=C(C(C(C(C)(CC(N[C@H](C(NCCC2=CC=C(OC)C=C2)=O)CC[C@H](NCC3=CC=CC=C3)C[C@@H]4[C@@H](O)[C@@H](O)[C@@H](O4)N5C=NC6=C5N=CN=C6N)=O)C)=C(C1=O)C)=O)C
  • InChI:
  • SKI-73: InChI=1S/C46H58N8O8/c1-26-27(2)39(57)36(28(3)38(26)56)46(4,5)21-35(55)53-33(44(60)49-19-18-29-12-15-32(61-6)16-13-29)17-14-31(23-48-22-30-10-8-7-9-11-30)20-34-40(58)41(59)45(62-34)54-25-52-37-42(47)50-24-51-43(37)54/h7-13,15-16,24-25,31,33-34,40-41,45,48,58-59H,14,17-23H2,1-6H3,(H,49,60)(H,53,55)(H2,47,50,51)/t31-,33-,34+,40+,41+,45+/m0/s1
  • SKI-73N: InChI=1S/C45H56N8O8/c1-25-26(2)38(56)35(27(3)37(25)55)45(4,5)21-34(54)52-32(43(59)47-19-18-28-12-15-31(60-6)16-13-28)17-14-30(48-22-29-10-8-7-9-11-29)20-33-39(57)40(58)44(61-33)53-24-51-36-41(46)49-23-50-42(36)53/h7-13,15-16,23-24,30,32-33,39-40,44,48,57-58H,14,17-22H2,1-6H3,(H,47,59)(H,52,54)(H2,46,49,50)/t30-,32-,33+,39+,40+,44+/m0/s1
  • InChIKey:
  • SKI-73: HZHUKQLWLNDVDZ-IBDVCRJISA-N
  • SKI-73N: NEMZJATUXVLJBZ-AEPDLXTASA-N
selectivity profile
in vitro potency
cell based assay data
references
pk properties
co-crystal structures

Main features

  • Overall structure of (S)-SKI-72 with PRMT4 showing dimeric crystal structure
  • PRMT4 with sinefungin and H3R17me
  • (S)-SKI-72 occupies both the SAM and peptide pockets
  • (S)-SKI-72 binding interactions
synthetic schemes
materials and methods
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