Background
Methods
Cells
Compounds
HTS and data analysis
Determination of GI50
Results and discussion
HTS identified over 100 compounds that significantly inhibit ovarian CSC growth
NSC | %growth | SD | p-value | p-adj (Holms) | GI
50(-log 10) OVCAR-3 |
---|---|---|---|---|---|
618332 | 3.3 | 4.0 | 3.73E-07 | 2.78E-04 | 5.08 |
219734 | 4.2 | 2.0 | 9.47E-07 | 6.88E-04 | 6.43 |
128305 | 4.9 | 3.4 | 8.02E-06 | 5.59E-03 | 4.34 |
168597 | 5.1 | 5.5 | 2.42E-06 | 1.73E-03 | 7.69 |
328426 | 5.3 | 3.2 | 4.64E-07 | 3.44E-04 | 7.62 |
143648 | 5.6 | 2.3 | 1.64E-07 | 1.23E-04 | 7.43 |
165563 | 6.1 | 4.4 | 3.58E-07 | 2.67E-04 | 8.05 |
145366 | 7.1 | 2.1 | 5.21E-08 | 4.00E-05 | 5.75 |
636132 | 7.3 | 3.2 | 9.47E-07 | 6.89E-04 | 4.00 |
323241 | 7.7 | 2.4 | 1.59E-07 | 1.20E-04 | 7.54 |
622732 | 8.0 | 4.9 | 4.93E-06 | 3.46E-03 | 4.90 |
208913 | 8.0 | 3.5 | 8.17E-07 | 5.96E-04 | 3.80 |
306864 | 8.0 | 3.1 | 3.86E-07 | 2.88E-04 | 5.76 |
4320 | 8.0 | 3.3 | 6.94E-08 | 5.31E-05 | 9.56 |
3053 | 8.4 | 3.9 | 1.38E-08 | 1.07E-05 | 8.54 |
265450 | 8.5 | 3.2 | 8.14E-08 | 6.21E-05 | 7.20 |
354844 | 8.6 | 6.0 | 4.34E-07 | 3.22E-04 | 7.26 |
164914 | 8.8 | 3.7 | 2.95E-09 | 2.32E-06 | 6.75 |
63701 | 8.9 | 3.4 | 1.00E-09 | 7.88E-07 | 7.46 |
697726 | 9.0 | 3.5 | 5.32E-09 | 4.16E-06 | 7.56 |
637578 | 9.1 | 2.3 | 1.04E-07 | 7.87E-05 | 8.36 |
614928 | 9.3 | 2.0 | 7.60E-07 | 5.56E-04 | 4.51 |
667467 | 9.8 | 3.9 | 3.53E-10 | 2.79E-07 | 4.00 |
65937 | 10.2 | 2.1 | 1.08E-07 | 8.16E-05 | - |
65423 | 10.4 | 3.1 | 2.61E-10 | 2.06E-07 | 5.78 |
690634 | 10.8 | 2.9 | 7.52E-07 | 5.51E-04 | 7.59 |
24559 | 10.8 | 3.6 | 9.91E-11 | 7.86E-08 | 7.35 |
18268 | 10.9 | 3.4 | 2.24E-08 | 1.73E-05 | 8.41 |
243023 | 11.0 | 3.4 | 4.48E-06 | 3.15E-03 | 8.07 |
635448 | 11.1 | 5.9 | 1.19E-08 | 9.27E-06 | 7.69 |
7525 | 11.3 | 2.4 | 4.99E-06 | 3.49E-03 | 7.60 |
616232 | 11.6 | 4.0 | 3.97E-10 | 3.13E-07 | 4.00 |
269754 | 11.9 | 8.4 | 1.62E-04 | 1.03E-01 | 8.10 |
680506 | 12.4 | 5.0 | 4.85E-07 | 3.58E-04 | - |
58514 | 12.5 | 3.1 | 1.34E-08 | 1.04E-05 | 9.52 |
353527 | 12.8 | 4.1 | 7.25E-07 | 5.32E-04 | 7.77 |
106408 | 12.8 | 2.4 | 1.29E-06 | 9.30E-04 | 7.34 |
620358 | 13.0 | 5.5 | 1.37E-05 | 9.27E-03 | 5.72 |
65104 | 13.2 | 4.3 | 9.57E-07 | 6.95E-04 | 8.76 |
325319 | 13.2 | 2.7 | 7.94E-07 | 5.80E-04 | 8.23 |
328166 | 13.4 | 5.4 | 4.72E-07 | 3.49E-04 | 7.35 |
658144 | 13.4 | 2.6 | 1.51E-08 | 1.17E-05 | 6.68 |
260610 | 13.9 | 5.5 | 2.48E-06 | 1.77E-03 | 6.79 |
631529 | 14.5 | 3.2 | 4.08E-07 | 3.04E-04 | 5.82 |
85236 | 14.5 | 2.5 | 8.67E-08 | 6.61E-05 | 5.82 |
376265 | 14.7 | 7.5 | 1.41E-05 | 9.53E-03 | 8.50 |
349644 | 14.9 | 4.6 | 2.95E-05 | 1.95E-02 | 7.72 |
89671 | 15.0 | 2.5 | 6.73E-07 | 4.95E-04 | 7.55 |
105808 | 15.3 | 3.8 | 1.15E-05 | 7.87E-03 | 5.96 |
635121 | 16.0 | 5.3 | 9.44E-06 | 6.53E-03 | 5.52 |
93419 | 17.1 | 7.4 | 2.92E-05 | 1.93E-02 | 6.13 |
268251 | 17.4 | 6.2 | 2.99E-06 | 2.12E-03 | 8.96 |
202000 | 17.7 | 5.0 | 3.03E-09 | 2.38E-06 | 4.05 |
659999 | 18.0 | 6.4 | 1.30E-08 | 1.01E-05 | 5.99 |
172924 | 18.5 | 3.1 | 7.81E-08 | 5.97E-05 | 6.67 |
673622 | 18.5 | 9.1 | 1.83E-05 | 1.23E-02 | 6.59 |
146604 | 19.2 | 4.6 | 2.41E-09 | 1.90E-06 | 6.65 |
349156 | 19.5 | 2.6 | 1.73E-06 | 1.24E-03 | 6.92 |
526417 | 19.7 | 3.8 | 5.38E-08 | 4.13E-05 | 9.28 |
400978 | 20.3 | 2.4 | 7.26E-09 | 5.67E-06 | 7.97 |
24817 | 20.4 | 5.8 | 2.23E-08 | 1.72E-05 | 7.67 |
319726 | 20.6 | 4.0 | 5.30E-09 | 4.15E-06 | 8.00 |
614826 | 20.8 | 5.2 | 1.41E-05 | 9.52E-03 | 6.66 |
679524 | 20.9 | 3.5 | 1.94E-10 | 1.54E-07 | 7.50 |
629301 | 20.9 | 5.5 | 2.23E-05 | 1.49E-02 | 4.80 |
129414 | 21.1 | 7.4 | 5.48E-05 | 3.58E-02 | 7.41 |
337766 | 21.4 | 5.8 | 1.20E-08 | 9.34E-06 | 6.73 |
7532 | 21.7 | 8.3 | 3.12E-06 | 2.21E-03 | 8.00 |
172946 | 21.7 | 5.6 | 1.25E-05 | 8.50E-03 | 7.46 |
328587 | 22.1 | 4.6 | 2.91E-09 | 2.29E-06 | 5.77 |
34391 | 22.2 | 4.2 | 4.20E-07 | 3.12E-04 | 5.60 |
153858 | 22.5 | 4.8 | 9.62E-07 | 6.97E-04 | 9.48 |
625483 | 22.8 | 9.7 | 2.53E-05 | 1.68E-02 | 4.66 |
82116 | 23.0 | 5.7 | 1.02E-07 | 7.75E-05 | - |
72961 | 23.1 | 4.4 | 1.27E-07 | 9.59E-05 | 5.60 |
65380 | 23.6 | 6.9 | 9.38E-05 | 6.03E-02 | 7.20 |
85700 | 23.7 | 4.7 | 1.18E-08 | 9.20E-06 | 5.98 |
336628 | 23.7 | 5.9 | 2.62E-07 | 1.97E-04 | 4.77 |
345647 | 23.8 | 48.5 | 1.03E-05 | 7.09E-03 | 6.59 |
102811 | 23.9 | 5.3 | 1.99E-08 | 1.54E-05 | 6.96 |
669356 | 24.5 | 8.1 | 2.09E-06 | 1.49E-03 | 8.00 |
7521 | 24.5 | 6.9 | 9.49E-05 | 6.08E-02 | 7.52 |
352876 | 24.7 | 6.7 | 4.35E-05 | 2.86E-02 | 6.27 |
148958 | 24.9 | 6.9 | 1.03E-07 | 7.81E-05 | 3.09 |
613009 | 25.0 | 5.7 | 3.89E-06 | 2.75E-03 | 7.41 |
10447 | 25.5 | 6.6 | 3.49E-07 | 2.61E-04 | 4.65 |
301460 | 25.6 | 5.0 | 2.20E-06 | 1.57E-03 | 8.00 |
605756 | 25.8 | 6.4 | 6.31E-07 | 4.65E-04 | 5.68 |
407806 | 26.5 | 3.1 | 1.95E-06 | 1.40E-03 | 7.44 |
67574 | 27.0 | 6.0 | 1.21E-06 | 8.74E-04 | 7.68 |
700582 | 27.2 | 5.8 | 1.02E-07 | 7.74E-05 | 6.57 |
304421 | 27.9 | 4.2 | 4.98E-06 | 3.49E-03 | 6.47 |
521777 | 28.1 | 6.1 | 3.29E-08 | 2.53E-05 | 8.00 |
330500 | 29.0 | 4.8 | 6.10E-07 | 4.50E-04 | 6.05 |
255109 | 29.6 | 4.9 | 1.15E-05 | 7.84E-03 | 7.02 |
302979 | 30.4 | 10.8 | 5.65E-05 | 3.68E-02 | 5.43 |
33410 | 30.8 | 5.6 | 6.80E-08 | 5.21E-05 | 7.98 |
693632 | 30.8 | 7.4 | 2.11E-07 | 1.58E-04 | 6.44 |
24818 | 31.0 | 5.3 | 9.92E-06 | 6.85E-03 | 8.12 |
24819 | 31.1 | 4.7 | 1.14E-06 | 8.25E-04 | 8.47 |
52141 | 31.3 | 6.0 | 1.14E-06 | 8.24E-04 | 7.14 |
96932 | 31.4 | 6.9 | 6.94E-07 | 5.10E-04 | 6.77 |
349155 | 31.7 | 7.1 | 1.99E-05 | 1.33E-02 | 6.45 |
97911 | 32.4 | 7.6 | 6.23E-05 | 4.05E-02 | 5.70 |
243928 | 32.5 | 9.0 | 8.80E-06 | 6.11E-03 | 5.69 |
83265 | 34.8 | 6.7 | 4.05E-06 | 2.86E-03 | 5.70 |
637993 | 34.8 | 9.9 | 8.30E-05 | 5.36E-02 | 5.50 |
145669 | 34.9 | 6.6 | 3.26E-07 | 2.44E-04 | 7.75 |
157930 | 34.9 | 6.5 | 5.26E-06 | 3.68E-03 | 6.16 |
132791 | 35.2 | 15.3 | 1.52E-04 | 9.67E-02 | 6.96 |
331757 | 35.6 | 15.4 | 1.55E-04 | 9.84E-02 | 5.11 |
269142 | 36.0 | 10.3 | 9.02E-06 | 6.25E-03 | 6.68 |
1906 | 36.2 | 3.5 | 4.46E-08 | 3.43E-05 | 4.15 |
14229 | 37.6 | 6.1 | 9.93E-08 | 7.56E-05 | 5.55 |
1620 | 37.7 | 8.4 | 4.88E-06 | 3.43E-03 | 4.00 |
622627 | 38.4 | 11.4 | 1.82E-05 | 1.22E-02 | 5.28 |
215989 | 38.6 | 7.1 | 2.91E-06 | 2.07E-03 | - |
13973 | 40.2 | 5.5 | 1.38E-06 | 9.94E-04 | 6.28 |
332598 | 40.6 | 7.4 | 2.18E-05 | 1.45E-02 | 10.38 |
126727 | 41.3 | 11.0 | 6.20E-05 | 4.04E-02 | - |
248436 | 41.4 | 9.5 | 1.35E-05 | 9.15E-03 | 4.08 |
705330 | 41.6 | 10.5 | 1.35E-05 | 9.17E-03 | 5.70 |
166454 | 41.9 | 7.2 | 8.76E-07 | 6.39E-04 | 5.41 |
84074 | 42.9 | 7.3 | 1.84E-05 | 1.23E-02 | 5.46 |
632841 | 43.2 | 6.1 | 1.47E-06 | 1.06E-03 | 5.83 |
116693 | 43.6 | 5.1 | 1.86E-07 | 1.40E-04 | 5.50 |
375575 | 44.8 | 5.1 | 1.04E-05 | 7.14E-03 | 5.71 |
98904 | 45.5 | 11.5 | 1.23E-04 | 7.85E-02 | 6.05 |
629971 | 46.5 | 10.7 | 1.01E-05 | 6.96E-03 | 6.54 |
403883 | 48.3 | 7.0 | 2.37E-05 | 1.57E-02 | 4.00 |
267033 | 48.5 | 10.9 | 4.31E-05 | 2.84E-02 | 6.35 |
36437 | 48.5 | 5.5 | 8.51E-06 | 5.91E-03 | 5.23 |
49842 | 49.1 | 10.6 | 2.34E-05 | 1.56E-02 | 9.71 |
654259 | 49.8 | 9.0 | 2.57E-06 | 1.83E-03 | 7.23 |
182986 | 50.1 | 9.1 | 1.52E-05 | 1.02E-02 | 5.27 |
93739 | 50.4 | 6.5 | 1.54E-05 | 1.04E-02 | 5.40 |
NSC | Name | % growth | SD (%) | p-value | p-adj | GI
50OVCAR3 (−log10) |
---|---|---|---|---|---|---|
3053 | Dactinomycin | 8.4 | 3.9 | 1.38E-08 | 1.07E-05 | 8.54 |
24559 | Plicamycin | 10.8 | 3.6 | 9.91E-11 | 7.86E-08 | 7.35 |
67574 | Vincristine | 27.0 | 6.0 | 1.21E-06 | 8.74E-04 | 7.68 |
14229 | Mepacrine | 37.6 | 6.1 | 9.93E-08 | 7.56E-05 | 5.55 |
49842 | Vinblastine | 49.1 | 10.6 | 2.34E-05 | 1.56E-02 | 9.71 |
125066 | Bleomycin | 53.0 | 10.2 | 1.10E-05 | 7.54E-03 | 5.28 |
63878 | Cytarabine | 76.6 | 11.0 | 1.04E-02 | 1 | 5.00 |
105014 | Cladribine | 82.7 | 17.0 | 7.13E-02 | 1 | 4.59 |
755 | Mercaptopurine | 95.2 | 8.4 | 2.83E-01 | 1 | 5.94 |
740 | Methotrexate | 96.7 | 30.8 | 8.38E-01 | 1 | 6.69 |
226080 | Rapamycin | 97.0 | 20.9 | 7.93E-01 | 1 | 8.17 |
296961 | Amifostine | 99.4 | 12.0 | 9.18E-01 | 1 | 3.13 |
85998 | Streptozocin | 103.7 | 28.9 | 8.10E-01 | 1 | 3.14 |
32065 | Hydroxyurea | 107.4 | 14.8 | 2.38E-01 | 1 | 2.92 |
180973 | Tamoxifen | 115.1 | 14.3 | 4.45E-02 | 1 | 5.23 |
750 | Busulfan | 120.6 | 15.9 | 3.65E-02 | 1 | 3.60 |
38721 | Mitotane | 128.2 | 47.6 | 2.68E-01 | 1 | 4.73 |
9706 | Triethylenemelamine | 128.9 | 82.5 | 5.26E-01 | 1 | 4.74 |
45388 | Dacarbazine | 164.3 | 14.2 | 4.46E-04 | 2.68E-01 | 4.25 |
Most ovarian CSC growth-inhibiting compounds also inhibit the growth of more differentiated ovarian cancer cells
NSC | Name | % growth | SD | p-adj |
---|---|---|---|---|
618332 | 2,3-Dibromonaphthoquinone | 3.3 | 4.0 | 2.78E-04 |
128305 | 5,7-Dihydroxy-3',4'-dimethoxyflavone | 4.9 | 3.4 | 5.59E-03 |
636132 | 3-Cyano-N,3-bis(2-methylphenyl)-2-oxopropanamide | 7.3 | 3.2 | 6.89E-04 |
622732 | N-(4-chlorophenyl)-1-methyl-1H-pyrazolo[3,4-b]quinolin-5-amine | 8.0 | 4.9 | 3.46E-03 |
208913 | Ethyl 2-(((1-adamantyl(methyl)amino) carbonyl)amino)propanoate | 8.0 | 3.5 | 5.96E-04 |
614928 | 3,3,4,4-Tetramethyltetrahydro-2,5-furandiol | 9.3 | 2.0 | 5.56E-04 |
667467 | 2-Phenyl-1,4-thiazino[3,2-c]quinoline-3-thione | 9.8 | 3.9 | 2.79E-07 |
616232 | Dibromodulcitol | 11.6 | 4.0 | 3.13E-07 |
635121 | N'-(1-(4H-1,4-benzothiazin-2-yl)ethylidene)-2-hydroxybenzohydrazide | 16.0 | 5.3 | 6.53E-03 |
202000 | (4Z)-4-[(3,4-dichlorophenyl) methylidene]-2-(furan-2-yl)-1,3-oxazol-5-one | 17.7 | 5.0 | 2.38E-06 |
629301 | 3,6-Dihydro-3,6-ethanocyclohepta[cd]
[1]benzofuran-10,10,11,11-tetracarbonitrile | 20.9 | 5.5 | 1.49E-02 |
34391 | Cryptocyanine iodide | 22.2 | 4.2 | 3.12E-04 |
625483 | 1-(2-Chloro-6-fluorophenyl)-1H,3H-Thiazolo(3,4-a)benzimidazole | 22.8 | 9.7 | 1.68E-02 |
72961 | 8-Azaadenosine | 23.1 | 4.4 | 9.59E-05 |
336628 | Merbarone | 23.7 | 5.9 | 1.97E-04 |
148958 | Ftorafur | 24.9 | 6.9 | 7.81E-05 |
10447 | Purpurin | 25.5 | 6.6 | 2.61E-04 |
302979 | Shikoccin | 30.4 | 10.8 | 3.68E-02 |
637993 | 6H-Imidazo[4,5,1-de]acridin-6-one, 5-[2-(diethylamino) ethylamino]-8-methox`y-1-methyl-, dihydrochloride | 34.8 | 9.9 | 5.36E-02 |
331757 | 2-Anthracenecarboxamide, N-[4-(diethylamino)-1-methylbutyl]-9,10-dihydro-9,10-dioxo-, monohydrochloride | 35.6 | 15.4 | 9.84E-02 |
1906 | Piperidinium piperidinedithiocarbamate | 36.2 | 3.5 | 3.43E-05 |
14229 | Mepacrine | 37.6 | 6.1 | 7.56E-05 |
1620 | 4-[[(2-furanyl)methyl]amino]-1H-pyrazolo[3,4-D]pyrimidine | 37.7 | 8.4 | 3.43E-03 |
622627 | 2-(chloromethyl)-1,3-dinitro-5-(trifluoromethyl)benzene | 38.4 | 11.4 | 1.22E-02 |
248436 | Platinum, dibromo(6-thioguanosine-N7,S6)-, (SP-4-3)- | 41.4 | 9.5 | 9.15E-03 |
166454 | Decamine | 41.9 | 7.2 | 6.39E-04 |
84074 | Phosphonium, (3-bromopropyl)triphenyl- bromide | 42.9 | 7.3 | 1.23E-02 |
116693 | 2,3-bis(benzoyloxy)succinic acid compound with 1,4-dimethyl-2-((4-methylphenyl)(phenyl)-l 4-sulfanyl)benzene (1:1) | 43.6 | 5.1 | 1.40E-04 |
403883 | Cedran-8-ol | 48.3 | 7.0 | 1.57E-02 |
36437 | Crassin acetate | 48.5 | 5.5 | 5.91E-03 |
182986 | Diaziquone | 50.1 | 9.1 | 1.02E-02 |
93739 | Fuchsine | 50.4 | 6.5 | 1.04E-02 |
Computational model classifies CSC inhibitory compounds into predicted cellular response groups
F | J | M | N | P | Q | R | S | V | |
---|---|---|---|---|---|---|---|---|---|
(a)
| 29 (4.2%) | 44 (6.4%) | 129 (18.7%) | 102 (14.8%) | 92 (13.3%) | 83 (12.0%) | 25 (3.6%) | 140 (20.3%) | 46 (6.7%) |
(b)
| 5 (2.6%) | 7 (3.6%) | 70 (36.1%) | 16 (8.2%) | 25 (12.9%) | 13 (6.7%) | 5 (2.6%) | 42 (21.6%) | 11 (5.7%) |
(c)
| 3 (1.9%) | 5 (3.1%) | 62 (38.5%) | 16 (9.9%) | 19 (11.8%) | 9 (5.6%) | 3 (1.9%) | 35 (21.7%) | 9 (5.6%) |
(d)
| 2 (7.4%) | 1 (3.7%) | 6 (22.2%) | 0 (0%) | 5 (18.5%) | 4 (14.8%) | 1 (3.7%) | 7 (25.9%) | 1 (3.7%) |
p-ab
| 0.3988 | 0.1653 | <0.0001 | 0.0169 | 1.0000 | 0.0365 | 0.6537 | 0.6882 | 0.7412 |
p-ac
| 0.2469 | 0.1326 | <0.0001 | 0.1283 | 0.6970 | 0.0163 | 0.3325 | 0.6663 | 0.7235 |
p-ad
| Numbers too small for statistical evaluation |