Non-specific chemical inhibition of the Fanconi anemia pathway sensitizes cancer cells to cisplatin

Table 1 List of the validated small molecule inhibitors of the FA pathway

Chemicals	Primary known functions	IC50 (μM)
Lactacystin	Proteasome inhibitor	1.7
MG132	Proteasome and calpain inhibitor	0.8
ALLN	Proteasome, calpain, cathepsin L inhibitor	9.2
5929407	Proteasome inhibitor (this study)	6.5
Curcumin	Proteasome, protein kinase C (PKC), EGF-receptor tyrosine kinase, IkappaB kinase and mTOR inhibitor	18.6
H-9	PKA, PKC, PKG inhibitor	34.2
Gö6976	PKC, CHK1 inhibitor	> 50
SB218078	CHK1, Cdc2, PKC inhibitor	1.4
UCN-01	PKC, CHK1, CDK, AKT inhibitor	0.14
Alsterpaullone	CDK, GSK3 inhibitor	1.6
Roscovitine	CDK, ERK1,2 inhibitor	27.5
Geldanamycin	HSP90 inhibitor	0.15
17-AAG	HSP90 inhibitor	0.6
CA-074-Me	CathepsinB inhibitor	16.7
Chloroquine	Lysosome permeabilisation, inhibition of drug efflux pumps (ATP-binding cassette transporters)	67.5
Wortmannin	Casein kinase II, phosphatidylinositol 3-kinase (PI 3-kinase), polo-like kinase 1 (PLK1) inhibitor	84.4
DRB	Casein kinase II, RNA pol II inhibitor	11
HNMPA-(AM)3	Insulin receptor tyrosine kinase inhibitor	4.7
Puromycin	Protein synthesis inhibitor	5.2
TPEN	Heavy metal chelator	5
5656325	Unknown	0.83
5315179	Unknown	5.9
7012246	Unknown	7
5195243	Unknown	2.2
5373662	Unknown	1.3

The identified chemicals are presented with their major known functions and the dose required to inhibit 50% of IR-induced EGFP-FANCD2 foci formation (IC50) in PD20-EGFP-FANCD2 cells. Chemical structures of 5195243 (2-nitro-9,10-phenanthrenedione 10-oxime), 5373662 (2-(2-pyrinylmethylene)quinuclidin-3-one), 5656325 (1-(2-methoxy-1-naphtyl)-3-(3-pyridinyl)-2-propen-1-one), 5929407 (5-[4-(dietylamino)benzylidene]-3-{[(3-methylphenyl)amino]methyl}-2-thioxo-1,3-thiazolidin-4-one), 5315179 (1-(2,4-dimethoxyphenyl)-3-(3-pyridinyl)-2-propen-1-one) and 7012246 (1-(5-bromo-2-hydroxyphenyl)-3-(3-pyridinyl)-2-propen-1-one)) are shown in Additional file 2: Figure S1.

ISSN: 1476-4598