Encoding BRAF Inhibitor Functions in Protein Degraders
Miller, Daniel; Voell, Sabine Anna; Sosič, Izidor; Proj, Matic; Rossanese, Olivia; Schnakenburg, Gregor; Gütschow, Michael; Collins, Ian; Steinebach, Christian; RSC Medicinal Chemistry  (2022) –; doi:10.1039/D2MD00064D

data_7244893
_publ_section_title
;
 Encoding BRAF Inhibitor Functions in Protein Degraders
;
_journal_name_full               'RSC Medicinal Chemistry'
_journal_paper_doi               10.1039/D2MD00064D
_journal_year                    2022
_chemical_formula_moiety         'C17 H14 Br F2 N3 O3 S'
_chemical_formula_sum            'C17 H14 Br F2 N3 O3 S'
_chemical_formula_weight         458.28
_chemical_name_systematic        SAV-18
_space_group_crystal_system      triclinic
_space_group_IT_number           2
_space_group_name_Hall           '-P 1'
_space_group_name_H-M_alt        'P -1'
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     direct
_audit_creation_date             2019-10-02
_audit_creation_method
;
Olex2 1.2
(compiled 2018.04.18 svn.r3501 for OlexSys, GUI svn.r5488)
;
_audit_update_record
;
2022-01-21 deposited with the CCDC.	2022-05-05 downloaded from the CCDC.
;
_cell_angle_alpha                90.654(4)
_cell_angle_beta                 91.728(4)
_cell_angle_gamma                103.495(4)
_cell_formula_units_Z            2
_cell_length_a                   6.4327(4)
_cell_length_b                   7.6898(6)
_cell_length_c                   18.8782(14)
_cell_measurement_reflns_used    6464
_cell_measurement_temperature    100
_cell_measurement_theta_max      30.10
_cell_measurement_theta_min      2.16
_cell_volume                     907.47(11)
_computing_cell_refinement       'SAINT V8.38A (?, 2016)'
_computing_data_reduction        'SAINT V8.38A (?, 2016)'
_computing_molecular_graphics    'Olex2 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 (Dolomanov et al., 2009)'
_computing_structure_refinement  'ShelXL (Sheldrick, 2015)'
_computing_structure_solution    'XS (Sheldrick, 2008)'
_diffrn_ambient_temperature      100
_diffrn_measured_fraction_theta_full 0.998
_diffrn_measured_fraction_theta_max 0.999
_diffrn_measurement_device_type  'Bruker X8-KappaApexII'
_diffrn_measurement_method       '\f and \w scans'
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0848
_diffrn_reflns_av_unetI/netI     0.0537
_diffrn_reflns_Laue_measured_fraction_full 0.998
_diffrn_reflns_Laue_measured_fraction_max 0.999
_diffrn_reflns_limit_h_max       8
_diffrn_reflns_limit_h_min       -8
_diffrn_reflns_limit_k_max       10
_diffrn_reflns_limit_k_min       -10
_diffrn_reflns_limit_l_max       24
_diffrn_reflns_limit_l_min       -24
_diffrn_reflns_number            33623
_diffrn_reflns_point_group_measured_fraction_full 0.998
_diffrn_reflns_point_group_measured_fraction_max 0.999
_diffrn_reflns_theta_full        25.242
_diffrn_reflns_theta_max         27.998
_diffrn_reflns_theta_min         2.724
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    2.423
_exptl_absorpt_correction_T_max  0.7460
_exptl_absorpt_correction_T_min  0.6154
_exptl_absorpt_correction_type   empirical
_exptl_absorpt_process_details
'SADABS-2016/2 (Bruker,2016/2) was used for absorption correction. wR2(int) was 0.1135 before and 0.0661 after correction. The Ratio of minimum to maximum transmission is 0.8249. The \l/2 correction factor is Not present.'
_exptl_crystal_colour            'clear colourless'
_exptl_crystal_colour_lustre     clear
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.677
_exptl_crystal_description       plank
_exptl_crystal_F_000             460
_exptl_crystal_size_max          0.22
_exptl_crystal_size_mid          0.08
_exptl_crystal_size_min          0.02
_refine_diff_density_max         0.736
_refine_diff_density_min         -0.785
_refine_diff_density_rms         0.090
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.009
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     245
_refine_ls_number_reflns         4393
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.009
_refine_ls_R_factor_all          0.0609
_refine_ls_R_factor_gt           0.0344
_refine_ls_shift/su_max          0.000
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
;
 w=1/[\s^2^(Fo^2^)+(0.0342P)^2^+0.6512P]
 where P=(Fo^2^+2Fc^2^)/3
;
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0745
_refine_ls_wR_factor_ref         0.0841
_reflns_Friedel_coverage         0.000
_reflns_number_gt                3301
_reflns_number_total             4393
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d2md00064d2.cif
_cod_data_source_block           6145f
_cod_database_code               7244893
_shelxl_version_number           2013-2
_shelx_estimated_absorpt_t_max   0.953
_shelx_estimated_absorpt_t_min   0.618
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups, All N(H) groups
 At 1.5 times of:
  All C(H,H,H) groups
2.a Riding coordinates:
 N3(H3)
2.b Secondary CH2 refined with riding coordinates:
 C15(H15A,H15B), C16(H16A,H16B)
2.c Aromatic/amide H refined with riding coordinates:
 N1(H1), C3(H3A), C5(H5), C7(H7), C12(H12), C13(H13)
2.d Idealised Me refined as rotating group:
 C17(H17A,H17B,H17C)
;
_shelx_res_checksum              90220
_olex2_submission_special_instructions 'No special instructions were received'