Chlorine in PDB 6uvh: Crystal Structure of Bcl-Xl Bound to Compound 15: (R)-2-(3-(2-((4'- Chloro-[1,1'-Biphenyl]-2-Yl)Methyl)-1,2,3,4-Tetrahydroisoquinoline-6- Carbonyl)-3-(4-Methylbenzyl)Ureido)-3-((Cyclohexylmethyl)Sulfonyl) Propanoic Acid

The structure of Crystal Structure of Bcl-Xl Bound to Compound 15: (R)-2-(3-(2-((4'- Chloro-[1,1'-Biphenyl]-2-Yl)Methyl)-1,2,3,4-Tetrahydroisoquinoline-6- Carbonyl)-3-(4-Methylbenzyl)Ureido)-3-((Cyclohexylmethyl)Sulfonyl) Propanoic Acid, PDB code: 6uvh was solved by M.J.Roy, G.Lessene, P.E.Czabotar, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	30.26 / 2.19
Space group	C 1 2 1
Cell size a, b, c (Å), α, β, γ (°)	152.026, 65.931, 77.133, 90, 98.71, 90
R / Rfree (%)	20.7 / 23.7

The binding sites of Chlorine atom in the Crystal Structure of Bcl-Xl Bound to Compound 15: (R)-2-(3-(2-((4'- Chloro-[1,1'-Biphenyl]-2-Yl)Methyl)-1,2,3,4-Tetrahydroisoquinoline-6- Carbonyl)-3-(4-Methylbenzyl)Ureido)-3-((Cyclohexylmethyl)Sulfonyl) Propanoic Acid (pdb code 6uvh). This binding sites where shown within 5.0 Angstroms radius around Chlorine atom.
In total 4 binding sites of Chlorine where determined in the Crystal Structure of Bcl-Xl Bound to Compound 15: (R)-2-(3-(2-((4'- Chloro-[1,1'-Biphenyl]-2-Yl)Methyl)-1,2,3,4-Tetrahydroisoquinoline-6- Carbonyl)-3-(4-Methylbenzyl)Ureido)-3-((Cyclohexylmethyl)Sulfonyl) Propanoic Acid, PDB code: 6uvh:
Jump to Chlorine binding site number: 1; 2; 3; 4;

Chlorine binding site 1 out of 4 in the Crystal Structure of Bcl-Xl Bound to Compound 15: (R)-2-(3-(2-((4'- Chloro-[1,1'-Biphenyl]-2-Yl)Methyl)-1,2,3,4-Tetrahydroisoquinoline-6- Carbonyl)-3-(4-Methylbenzyl)Ureido)-3-((Cyclohexylmethyl)Sulfonyl) Propanoic Acid


Mono view


Stereo pair view

A full contact list of Chlorine with other atoms in the Cl binding site number 1 of Crystal Structure of Bcl-Xl Bound to Compound 15: (R)-2-(3-(2-((4'- Chloro-[1,1'-Biphenyl]-2-Yl)Methyl)-1,2,3,4-Tetrahydroisoquinoline-6- Carbonyl)-3-(4-Methylbenzyl)Ureido)-3-((Cyclohexylmethyl)Sulfonyl) Propanoic Acid within 5.0Å range: probe atom residue distance (Å) B Occ A:Cl303 b:51.0 occ:1.00 CL A:QHJ303 0.0 51.0 1.0 C A:QHJ303 1.7 43.9 1.0 C1 A:QHJ303 2.7 39.0 1.0 C3 A:QHJ303 2.7 40.0 1.0 CD1 A:PHE105 3.1 44.5 1.0 OG A:SER145 3.4 40.2 0.5 CE1 A:PHE105 3.8 44.7 1.0 CE2 A:PHE97 3.9 41.0 1.0 C2 A:QHJ303 4.0 41.2 1.0 C4 A:QHJ303 4.0 39.5 1.0 N A:PHE146 4.1 32.2 1.0 CG A:PHE105 4.2 42.6 1.0 CA A:PHE146 4.2 31.7 1.0 CA A:PHE105 4.2 39.1 1.0 CD2 A:LEU108 4.3 38.4 1.0 C A:SER145 4.4 35.4 1.0 CB A:SER145 4.4 34.3 0.5 CB A:PHE105 4.4 40.9 1.0 CB A:SER145 4.4 29.9 0.5 C5 A:QHJ303 4.5 40.9 1.0 CB A:PHE146 4.5 33.4 1.0 O A:ALA142 4.6 36.1 1.0 O A:SER145 4.6 34.2 1.0 CZ A:PHE97 4.7 38.6 1.0 CD2 A:PHE97 4.9 39.3 1.0 O A:PHE105 4.9 42.2 1.0

Chlorine binding site 2 out of 4 in the Crystal Structure of Bcl-Xl Bound to Compound 15: (R)-2-(3-(2-((4'- Chloro-[1,1'-Biphenyl]-2-Yl)Methyl)-1,2,3,4-Tetrahydroisoquinoline-6- Carbonyl)-3-(4-Methylbenzyl)Ureido)-3-((Cyclohexylmethyl)Sulfonyl) Propanoic Acid


Mono view


Stereo pair view

A full contact list of Chlorine with other atoms in the Cl binding site number 2 of Crystal Structure of Bcl-Xl Bound to Compound 15: (R)-2-(3-(2-((4'- Chloro-[1,1'-Biphenyl]-2-Yl)Methyl)-1,2,3,4-Tetrahydroisoquinoline-6- Carbonyl)-3-(4-Methylbenzyl)Ureido)-3-((Cyclohexylmethyl)Sulfonyl) Propanoic Acid within 5.0Å range: probe atom residue distance (Å) B Occ B:Cl301 b:77.0 occ:1.00 CL B:QHJ301 0.0 77.0 1.0 C B:QHJ301 1.7 77.8 1.0 C1 B:QHJ301 2.7 79.8 1.0 C3 B:QHJ301 2.7 78.7 1.0 CD1 B:PHE105 3.2 94.2 1.0 CE1 B:PHE105 3.7 94.6 1.0 N B:PHE146 3.9 52.3 1.0 CE2 B:PHE97 4.0 74.9 1.0 CA B:PHE146 4.0 52.1 1.0 C2 B:QHJ301 4.0 81.4 1.0 C4 B:QHJ301 4.0 79.9 1.0 C B:SER145 4.1 54.8 1.0 CB B:SER145 4.1 54.2 0.5 CG B:PHE105 4.2 91.3 1.0 CB B:SER145 4.2 53.7 0.5 CB B:PHE146 4.3 53.5 1.0 O B:ALA142 4.3 51.1 1.0 O B:SER145 4.3 55.0 1.0 CD2 B:LEU108 4.3 101.3 1.0 CA B:PHE105 4.4 88.8 1.0 CB B:PHE105 4.5 90.4 1.0 C5 B:QHJ301 4.5 81.7 1.0 CA B:SER145 4.8 51.0 0.5 CD2 B:PHE97 4.8 71.5 1.0 CA B:SER145 4.8 50.9 0.5 CZ B:PHE97 4.8 73.1 1.0

Chlorine binding site 3 out of 4 in the Crystal Structure of Bcl-Xl Bound to Compound 15: (R)-2-(3-(2-((4'- Chloro-[1,1'-Biphenyl]-2-Yl)Methyl)-1,2,3,4-Tetrahydroisoquinoline-6- Carbonyl)-3-(4-Methylbenzyl)Ureido)-3-((Cyclohexylmethyl)Sulfonyl) Propanoic Acid


Mono view


Stereo pair view

A full contact list of Chlorine with other atoms in the Cl binding site number 3 of Crystal Structure of Bcl-Xl Bound to Compound 15: (R)-2-(3-(2-((4'- Chloro-[1,1'-Biphenyl]-2-Yl)Methyl)-1,2,3,4-Tetrahydroisoquinoline-6- Carbonyl)-3-(4-Methylbenzyl)Ureido)-3-((Cyclohexylmethyl)Sulfonyl) Propanoic Acid within 5.0Å range: probe atom residue distance (Å) B Occ C:Cl301 b:57.8 occ:1.00 CL C:QHJ301 0.0 57.8 1.0 C C:QHJ301 1.7 51.2 1.0 C1 C:QHJ301 2.7 47.0 1.0 C3 C:QHJ301 2.7 48.4 1.0 CD1 C:PHE105 3.3 52.3 1.0 CE1 C:PHE105 3.9 53.0 1.0 CE2 C:PHE97 4.0 49.3 1.0 C2 C:QHJ301 4.0 46.0 1.0 C4 C:QHJ301 4.0 45.5 1.0 N C:PHE146 4.0 37.9 1.0 CA C:PHE146 4.1 37.1 1.0 CD2 C:LEU108 4.2 52.5 1.0 C C:SER145 4.2 42.2 1.0 CB C:SER145 4.2 40.7 1.0 CA C:PHE105 4.3 49.2 1.0 CG C:PHE105 4.3 50.1 1.0 O C:SER145 4.4 43.8 1.0 CB C:PHE105 4.5 49.9 1.0 CB C:PHE146 4.5 38.9 1.0 C5 C:QHJ301 4.5 43.8 1.0 O C:ALA142 4.6 40.4 1.0 CZ C:PHE97 4.7 47.3 1.0 CB C:LEU108 4.9 44.0 1.0 CA C:SER145 4.9 38.8 1.0 CD2 C:PHE97 4.9 46.7 1.0 CG C:LEU108 5.0 48.5 1.0

Chlorine binding site 4 out of 4 in the Crystal Structure of Bcl-Xl Bound to Compound 15: (R)-2-(3-(2-((4'- Chloro-[1,1'-Biphenyl]-2-Yl)Methyl)-1,2,3,4-Tetrahydroisoquinoline-6- Carbonyl)-3-(4-Methylbenzyl)Ureido)-3-((Cyclohexylmethyl)Sulfonyl) Propanoic Acid


Mono view


Stereo pair view

A full contact list of Chlorine with other atoms in the Cl binding site number 4 of Crystal Structure of Bcl-Xl Bound to Compound 15: (R)-2-(3-(2-((4'- Chloro-[1,1'-Biphenyl]-2-Yl)Methyl)-1,2,3,4-Tetrahydroisoquinoline-6- Carbonyl)-3-(4-Methylbenzyl)Ureido)-3-((Cyclohexylmethyl)Sulfonyl) Propanoic Acid within 5.0Å range: probe atom residue distance (Å) B Occ D:Cl302 b:77.6 occ:1.00 CL D:QHJ302 0.0 77.6 1.0 C D:QHJ302 1.7 80.2 1.0 C1 D:QHJ302 2.7 81.0 1.0 C3 D:QHJ302 2.7 83.9 1.0 CD1 D:PHE105 3.3 102.6 1.0 N D:PHE146 3.5 47.9 1.0 CA D:PHE146 3.5 49.0 1.0 CB D:PHE146 3.6 51.1 1.0 O D:ALA142 3.7 53.1 1.0 CE1 D:PHE105 3.7 102.7 1.0 CE2 D:PHE97 3.8 62.4 1.0 C2 D:QHJ302 4.0 86.1 1.0 C4 D:QHJ302 4.0 87.2 1.0 C D:SER145 4.0 51.0 1.0 CB D:SER145 4.2 49.7 0.5 CB D:SER145 4.2 51.3 0.5 CA D:PHE105 4.3 98.1 1.0 CG D:PHE105 4.4 100.3 1.0 CZ D:PHE97 4.4 61.2 1.0 O D:SER145 4.4 51.5 1.0 C5 D:QHJ302 4.5 90.1 1.0 CG D:PHE146 4.6 53.8 1.0 CD1 D:PHE146 4.6 56.5 1.0 C D:ALA142 4.6 53.3 1.0 CD2 D:LEU108 4.7 105.8 1.0 CA D:SER145 4.7 47.8 0.5 CA D:SER145 4.8 48.1 0.5 N D:PHE105 4.8 98.4 1.0 CB D:PHE105 4.8 99.5 1.0 CD2 D:PHE97 4.8 60.1 1.0 CA D:ALA142 4.9 51.5 1.0 CZ D:PHE105 5.0 101.4 1.0

M.J.Roy, A.Vom, T.Okamoto, B.J.Smith, R.W.Birkinshaw, S.Marcuccio, J.B.Baell, H.Yang, H.Abdo, D.C.S.Huang, P.M.Colman, P.E.Czabotar, G.Lessene. Structure-Guided Development of Potent Benzoylurea Inhibitors of Bcl-Xl and Bcl-2 J.Med.Chem. 2021.
ISSN: ISSN 0022-2623
DOI: 10.1021/ACS.JMEDCHEM.0C01771