Inhibitors of the Fanconi anaemia pathway

Target Broad /specific Mechanism of action Synergy with chemotherapy Direct Binding shown ICL inhibition demonstrated Cancer type investigated Part of pathway inhibited Reference
Curcumin Unknown Broad Proteasome and kinase inhibitor Cisplatin, not paclitaxol No FANCD2 monoubiquitylation and foci Ovarian FANCD2/I activation [147]
Wortmannin Unknown Broad Kinase inhibitor No No FANCD2 monoubiquitylation and foci Ovarian FANCD2/I activation [72, 146]
H-9 Unknown Broad Kinase inhibitor No No FANCD2 monoubiquitylation and foci Ovarian FANCD2/I activation [72, 147]
Alsterpaullone Unknown Broad Kinase inhibitor No No FANCD2 monoubiquitylation and foci Ovarian FANCD2/I activation [72, 147]
DDN Unknown Broad Unknown Cisplatin No FANCD2 monoubiquitylation and foci Ovarian FANCD2/I activation [149]
Bortezomib Unknown Broad Proteasome inhibitor Cisplatin No FANCD2 monoubiquitylation and foci, RAD51 foci Ovarian FANCD2/I activation [72]
17-AAG Unknown Broad HSP90 inhibitor Cisplatin No FANCD2 monoubiquitylation and foci, RAD51 foci Ovarian FANCD2/I activation [72]
CA-074-Me Unknown Broad CathepsinB inhibitor Cisplatin No FANCD2 monoubiquitylation and foci, RAD51 foci Ovarian FANCD2/I activation [72]
Compound 7012246 Unknown Broad Unknown Cisplatin No FANCD2 monoubiquitylation and foci, RAD51 foci Ovarian FANCD2/I activation [72]
Compound 5373662 Unknown Broad Unknown Cisplatin No FANCD2 monoubiquitylation and foci, RAD51 foci Ovarian FANCD2/I activation [72]
Gö6976 Unknown Broad PKC, CHK1 inhibitor Cisplatin No FANCD2 foci, RAD51 foci Ovarian FANCD2/I activation [72]
SB218078 Unknown Broad CHK1, CDC2, PKC inhibitor Cisplatin No FANCD2 foci, RAD51 foci Ovarian FANCD2/I activation [72]
UCN-01 Unknown Broad PKC, CHK1, CDK, AKT inhibitor Cisplatin No FANCD2 monoubiquitylation and foci, RAD51 foci Ovarian FANCD2/I activation [72]
Geldanamycin Unknown Broad HSP90 inhibitor Cisplatin No FANCD2 monoubiquitylation and foci, RAD51 foci Ovarian FANCD2/I activation [72]
Chloroquine Unknown Broad Lysosome and drug pump inhibition Cisplatin No FANCD2 foci, RAD51 foci Ovarian FANCD2/I activation [72]
Puromycin Unknown Broad Protein Synthesis inhibitor Cisplatin No FANCD2 monoubiquitylation and foci, RAD51 foci Ovarian FANCD2/I activation [72]
EF24/4H-TTD IKK Broad IKK inhibitor MMC No FANCD2 monoubiquitylation and foci Cervical FANCD2/I activation [148]
Ouabain p38 kinase Broad Inhibitor of MMC induced S-phase arrest MMC No FANCD2 monoubiquitylation and foci, FANCD2/FANCI mRNA Osteosarcoma FANCD2/I activation [150]
MLN4924 NAE1 Specific Proteasome inhibitor MMC No FANCD2 monoubiquitylation and foci Ovarian, cervical FANCD2/I activation [151]
PIP-199 RMI/FANCM Specific Inhibition of protein-protein interaction Unknown Yes None None FANCD2/I activation [152]
CU2 UBE2T/FANCL Specific Inhibition of FANCD2 monoubiquitylation by FANCL Carboplatin No FANCD2 monoubiquitylation and foci Osteosarcoma FANCD2/I activation [88]
E-X PPI2 ERRC1/XPF Specific Inhibition of protein-protein interaction Cisplatin Yes None—NER focus Melanoma, ovarian Unhooking [153]
E-X AS5-4 ERRC1/XPF Specific Active site inhibitor Cisplatin Yes None—NER focus Melanoma Unhooking [153]
E-X AS5-7 ERRC1/XPF Specific Active site inhibitor Cisplatin No None—NER focus Melanoma Unhooking [153]
Compound 13 ERRC1/XPF Specific Active site inhibitor Cisplatin Yes None—NER focus Melanoma Unhooking [154]
Compound 7 REV7/REV3L Specific Inhibition of protein-protein interaction Cisplatin Yes None Cervical TLS [155]
Halenaquinone RAD51 Specific Inhibition of RAD51-dsDNA interaction Unknown Yes RAD51 homologous pairing None HR [156]
IBR2 RAD51 Specific RAD51 degradation by proteasome Imatinib Yes RAD51 foci, HR Chronic myeloid leukaemia HR [157]
B02 RAD51 Specific Inhibition of RAD51-DNA interaction Cisplatin (also in vivo) Yes RAD51 foci Breast HR [158, 159]
RI-1 RAD51 Specific Destabilization of RAD51 oligomerization MMC Yes RAD51 foci Breast, cervical, osteosarcoma HR [160]