Fluorine in PDB 8stg: Discovery and Clinical Validation of Rly-4008, the First Highly Selective FGFR2 Inhibitor with Activity Across FGFR2 Alterations and Resistance Mutations

Enzymatic activity of Discovery and Clinical Validation of Rly-4008, the First Highly Selective FGFR2 Inhibitor with Activity Across FGFR2 Alterations and Resistance Mutations

All present enzymatic activity of Discovery and Clinical Validation of Rly-4008, the First Highly Selective FGFR2 Inhibitor with Activity Across FGFR2 Alterations and Resistance Mutations:
2.7.10.1;

Protein crystallography data

The structure of Discovery and Clinical Validation of Rly-4008, the First Highly Selective FGFR2 Inhibitor with Activity Across FGFR2 Alterations and Resistance Mutations, PDB code: 8stg was solved by R.Valverde, L.Foster, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å) 56.30 / 3.79
Space group P 21 21 21
Cell size a, b, c (Å), α, β, γ (°) 62.51, 91.34, 129.62, 90, 90, 90
R / Rfree (%) 26.9 / 31.9

Fluorine Binding Sites:

The binding sites of Fluorine atom in the Discovery and Clinical Validation of Rly-4008, the First Highly Selective FGFR2 Inhibitor with Activity Across FGFR2 Alterations and Resistance Mutations (pdb code 8stg). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 2 binding sites of Fluorine where determined in the Discovery and Clinical Validation of Rly-4008, the First Highly Selective FGFR2 Inhibitor with Activity Across FGFR2 Alterations and Resistance Mutations, PDB code: 8stg:
Jump to Fluorine binding site number: 1; 2;

Fluorine binding site 1 out of 2 in 8stg

Go back to Fluorine Binding Sites List in 8stg
Fluorine binding site 1 out of 2 in the Discovery and Clinical Validation of Rly-4008, the First Highly Selective FGFR2 Inhibitor with Activity Across FGFR2 Alterations and Resistance Mutations


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 1 of Discovery and Clinical Validation of Rly-4008, the First Highly Selective FGFR2 Inhibitor with Activity Across FGFR2 Alterations and Resistance Mutations within 5.0Å range:
probe atom residue distance (Å) B Occ
A:F801

b:119.2
occ:1.00
F14 A:WCJ801 0.0 119.2 1.0
C13 A:WCJ801 1.3 116.8 1.0
C12 A:WCJ801 2.3 109.4 1.0
HB1 A:ALA643 2.4 70.6 1.0
C15 A:WCJ801 2.4 114.8 1.0
H121 A:WCJ801 2.6 135.3 1.0
O16 A:WCJ801 2.8 113.1 1.0
N23 A:WCJ801 2.8 85.3 1.0
HD2 A:PHE492 2.8 148.9 1.0
C17 A:WCJ801 2.9 96.2 1.0
HE2 A:PHE492 3.1 119.7 1.0
CD2 A:PHE492 3.1 120.7 1.0
CE2 A:PHE492 3.2 96.4 1.0
CB A:ALA643 3.3 55.5 1.0
H A:ASP644 3.5 104.7 1.0
HB3 A:ALA643 3.5 70.6 1.0
C24 A:WCJ801 3.6 109.1 1.0
C11 A:WCJ801 3.6 93.3 1.0
C22 A:WCJ801 3.7 118.2 1.0
N A:ASP644 3.8 83.8 1.0
N18 A:WCJ801 3.8 99.2 1.0
HB2 A:ALA643 3.9 70.6 1.0
HA A:ASP644 4.0 124.0 1.0
CG A:PHE492 4.0 132.6 1.0
HA A:ALA643 4.1 94.9 1.0
C25 A:WCJ801 4.1 114.2 1.0
CA A:ALA643 4.1 75.7 1.0
C A:ALA643 4.2 94.0 1.0
H221 A:WCJ801 4.2 145.8 1.0
CZ A:PHE492 4.2 104.6 1.0
HB2 A:PHE492 4.3 145.0 1.0
CA A:ASP644 4.5 100.0 1.0
C21 A:WCJ801 4.5 103.0 1.0
H241 A:WCJ801 4.5 134.9 1.0
C19 A:WCJ801 4.5 104.5 1.0
HB3 A:ASP644 4.7 155.1 1.0
HZ A:PHE492 4.7 129.5 1.0
CB A:PHE492 4.7 117.5 1.0
HG13 A:ILE548 4.8 140.5 1.0
HG21 A:ILE548 4.8 117.1 1.0
CD1 A:PHE492 4.9 107.7 1.0
C10 A:WCJ801 4.9 101.3 1.0
HB3 A:PHE492 4.9 145.0 1.0
C35 A:WCJ801 4.9 113.0 1.0
CE1 A:PHE492 4.9 97.7 1.0
HD11 A:LEU633 5.0 132.9 1.0

Fluorine binding site 2 out of 2 in 8stg

Go back to Fluorine Binding Sites List in 8stg
Fluorine binding site 2 out of 2 in the Discovery and Clinical Validation of Rly-4008, the First Highly Selective FGFR2 Inhibitor with Activity Across FGFR2 Alterations and Resistance Mutations


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 2 of Discovery and Clinical Validation of Rly-4008, the First Highly Selective FGFR2 Inhibitor with Activity Across FGFR2 Alterations and Resistance Mutations within 5.0Å range:
probe atom residue distance (Å) B Occ
B:F801

b:156.2
occ:1.00
F14 B:WCJ801 0.0 156.2 1.0
C13 B:WCJ801 1.3 143.3 1.0
C12 B:WCJ801 2.3 132.9 1.0
C15 B:WCJ801 2.4 137.8 1.0
H121 B:WCJ801 2.5 163.6 1.0
N23 B:WCJ801 2.5 151.3 1.0
HB1 B:ALA643 2.8 154.4 1.0
O16 B:WCJ801 2.8 141.6 1.0
CG B:PHE492 2.9 156.6 1.0
C17 B:WCJ801 2.9 129.1 1.0
CD2 B:PHE492 2.9 148.5 1.0
HB3 B:PHE492 3.0 184.6 1.0
O B:ALA643 3.1 161.3 1.0
HD2 B:PHE492 3.1 182.2 1.0
CB B:PHE492 3.3 150.4 1.0
HB2 B:PHE492 3.3 184.6 1.0
CD1 B:PHE492 3.4 148.0 1.0
CE2 B:PHE492 3.5 154.7 1.0
C22 B:WCJ801 3.5 161.0 1.0
C11 B:WCJ801 3.6 132.1 1.0
C24 B:WCJ801 3.6 136.0 1.0
CB B:ALA643 3.7 125.3 1.0
HB3 B:ALA643 3.8 154.4 1.0
H221 B:WCJ801 3.8 197.2 1.0
HD1 B:PHE492 3.8 181.7 1.0
CE1 B:PHE492 3.9 151.2 1.0
CZ B:PHE492 3.9 173.4 1.0
HE2 B:PHE492 4.0 189.7 1.0
C B:ALA643 4.0 139.3 1.0
N18 B:WCJ801 4.0 90.2 1.0
C25 B:WCJ801 4.1 149.5 1.0
HB2 B:ALA643 4.3 154.4 1.0
CA B:ALA643 4.4 125.8 1.0
C07 B:WCJ801 4.5 132.4 1.0
C21 B:WCJ801 4.5 156.3 1.0
HE1 B:PHE492 4.5 185.5 1.0
H241 B:WCJ801 4.5 167.3 1.0
HZ B:PHE492 4.6 212.1 1.0
C06 B:WCJ801 4.6 140.0 1.0
HA B:ALA643 4.6 154.9 1.0
C08 B:WCJ801 4.6 112.3 1.0
HZ3 B:LYS517 4.7 188.7 1.0
C19 B:WCJ801 4.7 96.3 1.0
H071 B:WCJ801 4.7 163.0 1.0
HZ2 B:LYS517 4.7 188.7 1.0
C10 B:WCJ801 4.8 105.4 1.0
CA B:PHE492 4.8 142.3 1.0
C35 B:WCJ801 4.9 129.1 1.0
HG21 B:VAL495 4.9 198.0 1.0
C05 B:WCJ801 4.9 116.5 1.0
HE2 B:LYS517 4.9 167.9 1.0
H061 B:WCJ801 5.0 172.1 1.0
C36 B:WCJ801 5.0 131.5 1.0

Reference:

V.Subbiah, V.Sahai, D.Maglic, K.Bruderek, B.B.Toure, S.Zhao, R.Valverde, P.J.O'hearn, D.T.Moustakas, H.Schonherr, N.Gerami-Moayed, A.M.Taylor, B.M.Hudson, D.J.Houde, D.Pal, L.Foster, H.Gunaydin, P.Ayaz, D.A.Sharon, L.Goyal, A.M.Schram, S.Kamath, C.A.Sherwin, O.Schmidt-Kittler, K.Y.Jen, F.Ricard, B.B.Wolf, D.E.Shaw, D.A.Bergstrom, J.Watters. Rly-4008, the First Highly Selective FGFR2 Inhibitor with Activity Across FGFR2 Alterations and Resistance Mutations Cancer Discov 2023.
ISSN: ESSN 2159-8290
DOI: 10.1158/2159-8290.CD-23-0475
Page generated: Sat Aug 3 00:06:58 2024

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