Table Info

Table 2.

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]

Declarations

Author contributions

SJT prepared the majority of the first draft while MJA and SPL contributed further sections. All authors contributed to manuscript revision, read and approved the submitted version.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

SJT, MJA and SPL gratefully acknowledges support from the Melville Trust for the Care and Cure of Cancer.

Copyright

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