Fluorine in PDB 8ts9: Human PI3K P85ALPHA/P110ALPHA H1047R Bound to Compound 1

The structure of Human PI3K P85ALPHA/P110ALPHA H1047R Bound to Compound 1, PDB code: 8ts9 was solved by M.Holliday, Y.Tang, A.Bulku, J.Wilbur, J.Fraser, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	95.67 / 2.83
Space group	P 21 21 21
Cell size a, b, c (Å), α, β, γ (°)	86.24, 120.469, 191.338, 90, 90, 90
R / Rfree (%)	23 / 25.2

The binding sites of Fluorine atom in the Human PI3K P85ALPHA/P110ALPHA H1047R Bound to Compound 1 (pdb code 8ts9). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 4 binding sites of Fluorine where determined in the Human PI3K P85ALPHA/P110ALPHA H1047R Bound to Compound 1, PDB code: 8ts9:
Jump to Fluorine binding site number: 1; 2; 3; 4;

Fluorine binding site 1 out of 4 in the Human PI3K P85ALPHA/P110ALPHA H1047R Bound to Compound 1


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 1 of Human PI3K P85ALPHA/P110ALPHA H1047R Bound to Compound 1 within 5.0Å range: probe atom residue distance (Å) B Occ A:F1101 b:92.0 occ:1.00 F24 A:UE91101 0.0 92.0 1.0 C23 A:UE91101 1.4 78.5 1.0 C25 A:UE91101 2.4 88.3 1.0 C22 A:UE91101 2.4 87.1 1.0 HD12 A:LEU911 2.5 89.9 1.0 HB3 A:LEU911 2.5 107.7 1.0 H251 A:UE91101 2.6 105.9 1.0 H221 A:UE91101 2.6 104.5 1.0 HD22 A:LEU911 2.9 100.8 1.0 HG22 A:THR813 3.1 93.6 1.0 CB A:LEU911 3.3 89.7 1.0 CD1 A:LEU911 3.4 74.9 1.0 HZ A:PHE1002 3.6 111.1 1.0 CG A:LEU911 3.6 77.2 1.0 HD11 A:ILE913 3.6 133.4 1.0 C26 A:UE91101 3.6 86.3 1.0 C21 A:UE91101 3.6 91.4 1.0 HB2 A:LEU911 3.7 107.7 1.0 CD2 A:LEU911 3.7 84.0 1.0 HA A:THR813 3.8 82.3 1.0 HG13 A:ILE913 3.8 116.3 1.0 HD11 A:LEU911 3.8 89.9 1.0 OG1 A:THR813 3.8 73.0 1.0 CG2 A:THR813 3.9 78.0 1.0 HD13 A:LEU911 4.0 89.9 1.0 HG21 A:THR813 4.0 93.6 1.0 HG12 A:ILE913 4.1 116.3 1.0 C27 A:UE91101 4.1 91.4 1.0 HE1 A:PHE1002 4.1 102.3 1.0 H131 A:UE91101 4.2 117.5 1.0 HD23 A:LEU911 4.2 100.8 1.0 O A:LEU911 4.3 84.7 1.0 CG1 A:ILE913 4.3 96.9 1.0 CZ A:PHE1002 4.3 92.6 1.0 CB A:THR813 4.3 67.1 1.0 HD21 A:LEU911 4.4 100.8 1.0 CD1 A:ILE913 4.4 111.2 1.0 HG1 A:THR813 4.5 87.5 1.0 CA A:LEU911 4.5 83.2 1.0 C13 A:UE91101 4.5 97.9 1.0 CA A:THR813 4.5 68.6 1.0 HA A:LEU911 4.5 99.8 1.0 CE1 A:PHE1002 4.6 85.2 1.0 HG A:LEU911 4.6 92.6 1.0 H181 A:UE91101 4.6 109.5 1.0 HG23 A:THR813 4.7 93.6 1.0 HG23 A:ILE816 4.7 80.2 1.0 H141 A:UE91101 4.8 114.5 1.0 HB A:ILE816 4.8 77.8 1.0 C14 A:UE91101 4.8 95.4 1.0 C A:LEU911 4.9 83.2 1.0 HG13 A:ILE816 4.9 86.7 1.0 C28 A:UE91101 4.9 85.8 1.0 C19 A:UE91101 4.9 91.4 1.0 HD13 A:ILE913 4.9 133.4 1.0

Fluorine binding site 2 out of 4 in the Human PI3K P85ALPHA/P110ALPHA H1047R Bound to Compound 1


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 2 of Human PI3K P85ALPHA/P110ALPHA H1047R Bound to Compound 1 within 5.0Å range: probe atom residue distance (Å) B Occ A:F1101 b:95.2 occ:1.00 F29 A:UE91101 0.0 95.2 1.0 C28 A:UE91101 1.4 85.8 1.0 F30 A:UE91101 2.2 94.5 1.0 F31 A:UE91101 2.2 82.8 1.0 C26 A:UE91101 2.3 86.3 1.0 HD21 A:LEU812 2.4 109.1 1.0 HD11 A:LEU1013 2.9 103.6 1.0 H251 A:UE91101 3.0 105.9 1.0 C25 A:UE91101 3.0 88.3 1.0 HD23 A:LEU812 3.1 109.1 1.0 CD2 A:LEU812 3.1 91.0 1.0 C27 A:UE91101 3.3 91.4 1.0 HD12 A:LEU1013 3.3 103.6 1.0 HB3 A:LEU812 3.4 91.1 1.0 HE1 A:PHE1002 3.5 102.3 1.0 H271 A:UE91101 3.5 109.6 1.0 CD1 A:LEU1013 3.6 86.3 1.0 HG A:LEU812 3.6 85.6 1.0 CG A:LEU812 3.8 71.3 1.0 HD22 A:LEU812 3.9 109.1 1.0 HA A:GLN809 3.9 93.6 1.0 HB2 A:GLU1012 4.0 98.0 1.0 CB A:LEU812 4.1 75.9 1.0 H163 A:UE91101 4.2 115.6 1.0 HG3 A:GLN809 4.2 105.1 1.0 HG A:LEU1013 4.2 92.7 1.0 H141 A:UE91101 4.2 114.5 1.0 HD13 A:LEU1013 4.2 103.6 1.0 HD1 A:PHE1002 4.3 90.2 1.0 C23 A:UE91101 4.3 78.5 1.0 CE1 A:PHE1002 4.3 85.2 1.0 HE1 A:MET1010 4.4 106.6 1.0 SD A:MET1010 4.4 94.0 1.0 CG A:LEU1013 4.5 77.3 1.0 HB2 A:LEU812 4.5 91.1 1.0 C21 A:UE91101 4.5 91.4 1.0 HG1 A:THR813 4.6 87.5 1.0 HB3 A:GLU1012 4.6 98.0 1.0 O A:GLN809 4.7 75.7 1.0 HD21 A:LEU1013 4.7 93.0 1.0 CD1 A:PHE1002 4.7 75.2 1.0 CB A:GLU1012 4.8 81.7 1.0 HE2 A:MET1010 4.8 106.6 1.0 CA A:GLN809 4.8 78.0 1.0 CE A:MET1010 4.8 88.9 1.0 HG2 A:GLU1012 4.9 115.5 1.0 OG1 A:THR813 4.9 73.0 1.0 C22 A:UE91101 4.9 87.1 1.0

Fluorine binding site 3 out of 4 in the Human PI3K P85ALPHA/P110ALPHA H1047R Bound to Compound 1


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 3 of Human PI3K P85ALPHA/P110ALPHA H1047R Bound to Compound 1 within 5.0Å range: probe atom residue distance (Å) B Occ A:F1101 b:94.5 occ:1.00 F30 A:UE91101 0.0 94.5 1.0 C28 A:UE91101 1.4 85.8 1.0 F29 A:UE91101 2.2 95.2 1.0 F31 A:UE91101 2.2 82.8 1.0 H271 A:UE91101 2.3 109.6 1.0 C26 A:UE91101 2.4 86.3 1.0 HB2 A:GLU1012 2.5 98.0 1.0 C27 A:UE91101 2.7 91.4 1.0 HG2 A:GLU1012 2.7 115.5 1.0 HG3 A:GLN809 2.9 105.1 1.0 CB A:GLU1012 3.1 81.7 1.0 HB3 A:GLU1012 3.2 98.0 1.0 CG A:GLU1012 3.2 96.2 1.0 CD A:GLU1012 3.5 91.2 1.0 OE1 A:GLU1012 3.5 91.4 1.0 C25 A:UE91101 3.6 88.3 1.0 CG A:GLN809 3.7 87.6 1.0 HG A:LEU938 3.7 124.9 1.0 HG2 A:GLN809 3.7 105.1 1.0 HA A:GLN809 3.9 93.6 1.0 H163 A:UE91101 4.0 115.6 1.0 H251 A:UE91101 4.0 105.9 1.0 C21 A:UE91101 4.1 91.4 1.0 HD12 A:LEU1013 4.1 103.6 1.0 HB3 A:GLN809 4.1 99.9 1.0 HG3 A:GLU1012 4.1 115.5 1.0 OE2 A:GLU1012 4.2 90.6 1.0 HD11 A:LEU1013 4.2 103.6 1.0 CB A:GLN809 4.3 83.2 1.0 HD21 A:LEU812 4.4 109.1 1.0 HG A:LEU1013 4.4 92.7 1.0 HE21 A:GLN809 4.4 92.2 1.0 HB3 A:MET1010 4.4 113.2 1.0 CA A:GLU1012 4.5 81.1 1.0 H A:GLU1012 4.6 100.4 1.0 CD1 A:LEU1013 4.6 86.3 1.0 CA A:GLN809 4.6 78.0 1.0 CG A:LEU938 4.7 104.1 1.0 C23 A:UE91101 4.8 78.5 1.0 SD A:MET1010 4.8 94.0 1.0 O20 A:UE91101 4.8 93.4 1.0 HD21 A:LEU938 4.8 128.6 1.0 CD A:GLN809 4.9 89.6 1.0 C22 A:UE91101 4.9 87.1 1.0 C19 A:UE91101 5.0 91.4 1.0 HD11 A:LEU938 5.0 116.3 1.0 NE2 A:GLN809 5.0 76.8 1.0 C16 A:UE91101 5.0 96.3 1.0

Fluorine binding site 4 out of 4 in the Human PI3K P85ALPHA/P110ALPHA H1047R Bound to Compound 1


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 4 of Human PI3K P85ALPHA/P110ALPHA H1047R Bound to Compound 1 within 5.0Å range: probe atom residue distance (Å) B Occ A:F1101 b:82.8 occ:1.00 F31 A:UE91101 0.0 82.8 1.0 C28 A:UE91101 1.4 85.8 1.0 F29 A:UE91101 2.2 95.2 1.0 F30 A:UE91101 2.2 94.5 1.0 C26 A:UE91101 2.4 86.3 1.0 HA A:GLN809 2.5 93.6 1.0 H251 A:UE91101 2.7 105.9 1.0 C25 A:UE91101 2.9 88.3 1.0 HG1 A:THR813 3.0 87.5 1.0 O A:GLN809 3.0 75.7 1.0 HB3 A:GLN809 3.0 99.9 1.0 HG3 A:GLN809 3.0 105.1 1.0 CA A:GLN809 3.2 78.0 1.0 CB A:GLN809 3.4 83.2 1.0 OG1 A:THR813 3.4 73.0 1.0 C A:GLN809 3.5 73.2 1.0 C27 A:UE91101 3.5 91.4 1.0 HB3 A:LEU812 3.5 91.1 1.0 CG A:GLN809 3.6 87.6 1.0 H271 A:UE91101 3.8 109.6 1.0 HD21 A:LEU812 3.8 109.1 1.0 HG2 A:GLN809 3.9 105.1 1.0 H A:THR813 4.2 77.8 1.0 C23 A:UE91101 4.2 78.5 1.0 HB2 A:GLN809 4.3 99.9 1.0 HG A:LEU938 4.4 124.9 1.0 HD21 A:LEU938 4.4 128.6 1.0 CB A:LEU812 4.4 75.9 1.0 N A:GLN809 4.5 83.0 1.0 HG A:LEU812 4.5 85.6 1.0 HD22 A:LEU938 4.6 128.6 1.0 HG2 A:GLU1012 4.6 115.5 1.0 N A:THR813 4.6 64.8 1.0 O A:ARG808 4.6 73.0 1.0 C21 A:UE91101 4.6 91.4 1.0 CD2 A:LEU812 4.6 91.0 1.0 HB2 A:GLU1012 4.8 98.0 1.0 CB A:THR813 4.8 67.1 1.0 N A:ASP810 4.8 76.4 1.0 CG A:LEU812 4.8 71.3 1.0 CD2 A:LEU938 4.9 107.2 1.0 C22 A:UE91101 4.9 87.1 1.0 HD23 A:LEU812 4.9 109.1 1.0 HB2 A:LEU812 4.9 91.1 1.0 CD A:GLN809 5.0 89.6 1.0 SD A:MET1010 5.0 94.0 1.0 H A:LEU812 5.0 82.4 1.0

A.Varkaris, E.Pazolli, H.Gunaydin, Q.Wang, L.Pierce, A.A.Boezio, L.Dipietro, A.Frost, F.Giordanetto, E.P.Hamilton, K.Harris, M.Holliday, T.L.Hunter, A.Iskandar, Y.Ji, A.Larivee, J.R.Larochelle, A.Lescarbeau, F.Llambi, B.Lormil, M.M.Mader, B.G.Mar, I.Martin, T.H.Mclean, K.Michelsen, Y.Pechersky, E.Puente-Poushnejad, R.Samadani, A.M.Schram, K.Shortsleeves, S.Swaminathan, S.Tajmir, G.Tan, Y.Tang, R.Valverde, B.Wehrenberg, J.Wilbur, B.R.Williams, H.Zeng, W.P.Walters, B.B.Wolf, D.E.Shaw, D.A.Bergstrom, J.Watters, J.S.Fraser, P.D.Fortin, D.R.Kipp. Discovery and Clinical Proof-of-Concept of Rly-2608, A First-in-Class Mutant-Selective Allosteric PI3KA Inhibitor That Decouples Anti-Tumor Activity From Hyperinsulinemia. Cancer Discov 2023.
ISSN: ESSN 2159-8290
PubMed: 37916956
DOI: 10.1158/2159-8290.CD-23-0944