NPASS Compound

Natural Product: NPC329675

Natural Product ID	NPC329675
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Madagascarensilide D
IUPAC Name	(3S,5S,8R,9S,10S,13R,14S,17R)-5,14-dihydroxy-3-[(2R,4S,5S,6R)-4-hydroxy-5-[(2S,4S,5R,6R)-4-methoxy-5-[(2S,4R,5S,6R)-4-methoxy-6-methyl-5-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]oxy-6-methyloxan-2-yl]oxy-6-methyloxan-2-yl]oxy-13-methyl-17-(5-oxo-2H-furan-3-yl)-2,3,4,6,7,8,9,11,12,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthrene-10-carbaldehyde
Synonyms	Madagascarensilide D
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1644524
PubChem CID	53322208
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0001125] Steroid lactones [CHEMONTID:0001555] Cardenolides and derivatives [CHEMONTID:0001559] Cardenolide glycosides and derivatives

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 3D 145153 0 0 0 0 0 0 0 0999 V2000 -0.5627 -0.5457 1.8359 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0905 0.3915 0.7972 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7343 0.4877 -0.4349 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2390 0.5535 -1.6124 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3432 1.5101 -1.0917 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1961 0.5981 -0.1972 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3159 -0.2200 0.5149 O 0 0 0 0 0 0 0 0 0 0 0 0 3.0762 1.2848 0.5854 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3751 1.2488 0.1573 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2153 2.4342 0.4872 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6566 2.0466 0.8486 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1588 0.9249 -0.0272 C 0 0 0 0 0 0 0 0 0 0 0 0 8.5602 0.5435 0.4734 C 0 0 0 0 0 0 0 0 0 0 0 0 9.4600 1.7179 0.4127 C 0 0 0 0 0 0 0 0 0 0 0 0 10.9258 1.2964 0.5677 C 0 0 0 0 0 0 0 0 0 0 0 0 11.2724 0.3798 -0.5907 C 0 0 0 0 0 0 0 0 0 0 0 0 12.6478 -0.1732 -0.4864 C 0 0 0 0 0 0 0 0 0 0 0 0 12.4925 -1.1983 0.6546 C 0 0 0 0 0 0 0 0 0 0 0 0 11.0351 -1.5956 0.6639 C 0 0 0 0 0 0 0 0 0 0 0 0 10.4237 -0.8819 -0.4881 C 0 0 0 0 0 0 0 0 0 0 0 0 8.9677 -0.6302 -0.3610 C 0 0 0 0 0 0 0 0 0 0 0 0 8.2427 -1.8561 0.1054 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9402 -1.4569 0.7660 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2571 -0.2848 0.1212 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0531 0.0925 1.0035 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6900 -0.6980 -1.0856 O 0 0 0 0 0 0 0 0 0 0 0 0 10.6412 -1.6045 -1.6671 O 0 0 0 0 0 0 0 0 0 0 0 0 13.7186 0.7720 -0.1830 C 0 0 0 0 0 0 0 0 0 0 0 0 14.4885 0.8015 0.8649 C 0 0 0 0 0 0 0 0 0 0 0 0 15.4373 1.9293 0.7659 C 0 0 0 0 0 0 0 0 0 0 0 0 16.3394 2.2795 1.5965 O 0 0 0 0 0 0 0 0 0 0 0 0 15.1867 2.5776 -0.4195 O 0 0 0 0 0 0 0 0 0 0 0 0 14.1254 1.9028 -1.0606 C 0 0 0 0 0 0 0 0 0 0 0 0 10.9683 1.1042 -1.8875 C 0 0 0 0 0 0 0 0 0 0 0 0 7.2367 1.4714 -1.3929 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9559 2.6582 -1.6380 O 0 0 0 0 0 0 0 0 0 0 0 0 0.7127 -0.6454 -2.0263 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.6561 -0.5144 -0.4764 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.9204 -0.1391 -0.8938 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4735 -1.1624 -1.8064 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3385 -2.1343 -0.9428 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5373 -1.3379 -0.5281 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1108 0.1317 -0.2734 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7938 0.1032 0.1936 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.4433 1.0627 -1.3455 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5809 -1.3991 -1.3981 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.8210 -1.4357 -0.8395 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.8410 -0.7690 -1.6547 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.1986 -1.4777 -1.5216 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.4318 -1.7576 -0.0313 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.3027 -2.6135 0.4399 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.2590 -2.7664 -0.4976 O 0 0 0 0 0 0 0 0 0 0 0 0 -9.7057 -3.9340 1.0341 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.4462 -0.5567 0.6462 O 0 0 0 0 0 0 0 0 0 0 0 0 -11.5745 -0.3175 1.4199 C 0 0 0 0 0 0 0 0 0 0 0 0 -11.2183 0.0928 2.7849 C 0 0 0 0 0 0 0 0 0 0 0 0 -11.3945 1.5170 3.1649 C 0 0 0 0 0 0 0 0 0 0 0 0 -12.3307 2.2865 2.2799 C 0 0 0 0 0 0 0 0 0 0 0 0 -12.2096 1.8717 0.8368 C 0 0 0 0 0 0 0 0 0 0 0 0 -12.3744 0.5494 0.6913 O 0 0 0 0 0 0 0 0 0 0 0 0 -10.9996 2.4713 0.1570 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.9495 3.8551 0.3942 O 0 0 0 0 0 0 0 0 0 0 0 0 -12.1326 3.6642 2.3595 O 0 0 0 0 0 0 0 0 0 0 0 0 -10.1447 2.1553 3.0398 O 0 0 0 0 0 0 0 0 0 0 0 0 -9.8972 -0.3109 3.0937 O 0 0 0 0 0 0 0 0 0 0 0 0 -11.2477 -0.7610 -2.0233 O 0 0 0 0 0 0 0 0 0 0 0 0 -11.9202 -1.4861 -3.0065 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6834 -3.2201 -1.7439 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0850 -4.3537 -1.2545 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3803 -0.0365 2.3716 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8764 -1.4508 1.2925 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2619 -0.8269 2.5279 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1732 1.3812 1.2721 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2391 1.5064 -0.4868 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2661 1.0825 -2.4232 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9148 2.3591 -0.5748 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9412 1.8082 -1.9436 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8050 0.0227 -0.9614 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3931 0.8752 -0.8805 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8309 2.8752 1.4652 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1756 3.2761 -0.2234 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7761 1.8257 1.9159 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3277 2.9295 0.5903 H 0 0 0 0 0 0 0 0 0 0 0 0 8.3959 0.2048 1.5258 H 0 0 0 0 0 0 0 0 0 0 0 0 9.2264 2.3715 1.2868 H 0 0 0 0 0 0 0 0 0 0 0 0 9.3882 2.2689 -0.5312 H 0 0 0 0 0 0 0 0 0 0 0 0 11.5267 2.2122 0.4736 H 0 0 0 0 0 0 0 0 0 0 0 0 11.0269 0.7699 1.5172 H 0 0 0 0 0 0 0 0 0 0 0 0 12.8350 -0.7780 -1.4051 H 0 0 0 0 0 0 0 0 0 0 0 0 12.7858 -0.7000 1.6008 H 0 0 0 0 0 0 0 0 0 0 0 0 13.1789 -2.0357 0.4760 H 0 0 0 0 0 0 0 0 0 0 0 0 10.5783 -1.4135 1.6517 H 0 0 0 0 0 0 0 0 0 0 0 0 11.0060 -2.6836 0.4337 H 0 0 0 0 0 0 0 0 0 0 0 0 8.6043 -0.4457 -1.4116 H 0 0 0 0 0 0 0 0 0 0 0 0 8.8153 -2.5227 0.7561 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9528 -2.4725 -0.7997 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0673 -1.2843 1.8557 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2177 -2.3152 0.6903 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3308 0.5221 1.9396 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3394 -0.7067 1.1294 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8788 -0.1179 -1.8250 H 0 0 0 0 0 0 0 0 0 0 0 0 9.8623 -2.2021 -1.7984 H 0 0 0 0 0 0 0 0 0 0 0 0 14.5291 0.1587 1.7319 H 0 0 0 0 0 0 0 0 0 0 0 0 13.3060 2.5894 -1.3149 H 0 0 0 0 0 0 0 0 0 0 0 0 14.4886 1.4646 -2.0364 H 0 0 0 0 0 0 0 0 0 0 0 0 9.9341 0.8388 -2.1733 H 0 0 0 0 0 0 0 0 0 0 0 0 11.6242 0.7045 -2.6572 H 0 0 0 0 0 0 0 0 0 0 0 0 11.0431 2.1945 -1.7006 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5380 0.8710 -2.2305 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2103 -0.6134 -2.8600 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8054 0.8591 -1.4094 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6305 -1.8177 -2.1648 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0211 -0.8211 -2.6793 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7056 -2.3737 -0.0989 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8345 -1.6342 0.5233 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7046 0.4388 0.6423 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5993 1.7631 -1.5377 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7632 0.6296 -2.3222 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2899 1.7396 -1.0183 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7248 -1.0275 0.1919 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.5479 -0.6892 -2.7223 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.0107 0.2615 -1.2976 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.1243 -2.4521 -2.0191 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.3611 -2.3285 0.1433 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.7874 -2.0442 1.2772 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.8687 -4.7383 0.2842 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.6569 -3.8452 1.6055 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.8715 -4.2652 1.6870 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.1665 -1.2865 1.3793 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.8440 -0.4983 3.5280 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.6801 1.6685 4.2202 H 0 0 0 0 0 0 0 0 0 0 0 0 -13.3814 2.1016 2.5990 H 0 0 0 0 0 0 0 0 0 0 0 0 -13.1125 2.3554 0.3307 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.0635 1.9829 0.4313 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.0753 2.3811 -0.9515 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.2340 4.3554 -0.4104 H 0 0 0 0 0 0 0 0 0 0 0 0 -13.0062 4.1382 2.3151 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.1390 3.0587 3.3984 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.5782 0.2867 3.8060 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.2579 -1.7461 -3.8564 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.7519 -0.8390 -3.3627 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.2982 -2.4477 -2.5771 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3730 -4.5891 -0.2134 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9893 -4.3505 -1.3190 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3952 -5.2631 -1.8607 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 6 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 24 26 1 0 20 27 1 0 17 28 1 0 28 29 2 0 29 30 1 0 30 31 2 0 30 32 1 0 32 33 1 0 16 34 1 0 12 35 1 0 35 36 2 0 4 37 1 0 3 38 1 0 38 39 1 0 39 40 1 0 40 41 1 0 41 42 1 0 42 43 1 0 43 44 1 0 43 45 1 0 42 46 1 0 46 47 1 0 47 48 1 0 48 49 1 0 49 50 1 0 50 51 1 0 51 52 1 0 51 53 1 0 50 54 1 0 54 55 1 0 55 56 1 0 56 57 1 0 57 58 1 0 58 59 1 0 59 60 1 0 59 61 1 0 61 62 1 0 58 63 1 0 57 64 1 0 56 65 1 0 49 66 1 0 66 67 1 0 41 68 1 0 68 69 1 0 7 2 1 0 25 9 1 0 24 12 1 0 21 13 1 0 20 16 1 0 33 28 1 0 44 39 1 0 52 47 1 0 60 55 1 0 1 70 1 0 1 71 1 0 1 72 1 0 2 73 1 0 3 74 1 0 4 75 1 0 5 76 1 0 5 77 1 0 6 78 1 0 9 79 1 0 10 80 1 0 10 81 1 0 11 82 1 0 11 83 1 0 13 84 1 0 14 85 1 0 14 86 1 0 15 87 1 0 15 88 1 0 17 89 1 0 18 90 1 0 18 91 1 0 19 92 1 0 19 93 1 0 21 94 1 0 22 95 1 0 22 96 1 0 23 97 1 0 23 98 1 0 25 99 1 0 25100 1 0 26101 1 0 27102 1 0 29103 1 0 33104 1 0 33105 1 0 34106 1 0 34107 1 0 34108 1 0 35109 1 0 37110 1 0 39111 1 0 40112 1 0 40113 1 0 41114 1 0 42115 1 0 43116 1 0 45117 1 0 45118 1 0 45119 1 0 47120 1 0 48121 1 0 48122 1 0 49123 1 0 50124 1 0 51125 1 0 53126 1 0 53127 1 0 53128 1 0 55129 1 0 56130 1 0 57131 1 0 58132 1 0 59133 1 0 61134 1 0 61135 1 0 62136 1 0 63137 1 0 64138 1 0 65139 1 0 67140 1 0 67141 1 0 67142 1 0 69143 1 0 69144 1 0 69145 1 0 M END

Standard InCHIKey	FNMTWOGECNNJOI-ASYHMFTESA-N
Standard InCHI	InChI=1S/C49H76O20/c1-23-42(67-37-17-32(59-5)43(24(2)63-37)68-38-18-33(60-6)44(25(3)64-38)69-45-41(56)40(55)39(54)34(20-50)66-45)31(52)16-36(62-23)65-27-7-12-47(22-51)29-8-11-46(4)28(26-15-35(53)61-21-26)10-14-49(46,58)30(29)9-13-48(47,57)19-27/h15,22-25,27-34,36-45,50,52,54-58H,7-14,16-21H2,1-6H3/t23-,24-,25-,27+,28-,29+,30-,31+,32+,33-,34-,36+,37+,38+,39-,40+,41-,42-,43-,44+,45+,46-,47+,48+,49+/m1/s1
SMILES	CC1C(C(CC(O1)OC2CCC3(C4CCC5(C(CCC5(C4CCC3(C2)O)O)C6=CC(=O)OC6)C)C=O)O)OC7CC(C(C(O7)C)OC8CC(C(C(O8)C)OC9C(C(C(C(O9)CO)O)O)O)OC)OC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	984.49	Volume:	946.947 ? Van der Waals volume.
Dense:	1.04	LogP:	0.785 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.397 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.218 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	13.0	Rigid Bonds:	51.0
TPSA:	277.28 ? Topological Polar Surface Area.	H-Bond Acceptor:	20.0
H-Bond Donor:	7.0	Rings:	9.0
Heavy Atoms:	20.0

MedChem Properties

QED Drug-Likeness Score:	0.076	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	6.693	Fsp³:	0.918
MCE-18:	174.128 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.0	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.005 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.157 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.414	Promiscuous compounds:	0.006

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.72	MDCK Permeability:	-5.101
Pgp-inhibitor:	0.0	Pgp-substrate:	0.997
PAMPA:	1.0 ? The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).	Human Intestinal Absorption (HIA):	0.998
20% Bioavailability (F20%):	0.344	30% Bioavailability (F30%):	0.94
50% Bioavailability (F50%):	0.996

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	0.998
Plasma Protein Binding (PPB):	40.71%	Volume Distribution (VD):	-0.514
Fu:	57.967% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.0
OATP1B3 inhibitor:	0.146	BCRP inhibitor:	0.0
BSEP inhibitor:	0.185

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.963	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.611	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.737	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.708	CYP2C8-inhibitor:	0.0
HLM stability:	0.0 ? Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):

0.496

Half-life (T1/2):

6.505

ADMET: Toxicity

hERG Blockers:	0.342	hERG Blockers (10um):	0.473
Human Hepatotoxicity (H-HT):	0.815	Drug-induced Liver Injury (DILI):	0.493
AMES Toxicity:	0.97	Rat Oral Acute Toxicity:	0.975
Maximum Recommended Daily Dose:	0.993	Skin Sensitization:	0.471
Carcinogencity:	0.258	Eye Corrosion:	0.0
Eye Irritation:	0.0	Respiratory Toxicity:	0.074
Drug-induced Neurotoxicity:	0.254	Ototoxicity:	0.999
Hematotoxicity:	0.039	Drug-induced Nephrotoxicity:	0.112
Genotoxicity:	0.997	RPMI-8226 Immunitoxicity:	0.756
A549 Cytotoxicity:	0.174	Hek293 Cytotoxicity:	0.983
BCF:	0.442 ? Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].	IGC50:	3.62 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.702 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.363 ? 96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO33348	leptadenia madagascariensis	Species	Apocynaceae	Eukaryota	n.a.	Madagascar dry forest	n.a.	PMID[21159516]
NPO33348	leptadenia madagascariensis	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

NP Quantity Composition/Concentration

Organism ID	Organism Name	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

Biological Activity

Activity Type	# Activity
IC50	2

Activity Type	# Activity
Cell line	2

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT179	Cell line	A2780	Homo sapiens	IC50	=	290.0	nM	PMID[7996553]
NPT397	Cell line	NCI-H460	Homo sapiens	IC50	=	480.0	nM	DOI[10.1016/S0960-894X(97)00439-3]

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

Experimental ADME

Experiment Model	Experiment Tissue	ADME Type	ADME Relation	ADME Value	ADME Unit	Reference

Experimental Toxicity

Quantitative toxicity

Experiment Model	Experiment Organism	Toxicity Type	Toxicity Relation	Toxicity Value	Toxicity Unit	Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity	Carcinogenicity	Mutagenicity	Cardiotoxicity	Respiratory Toxicity	Eye Irritation	Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]

Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

● The left chart: Distribution of similarity level between NPC329675 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	16985
0.1-0.2	28482
0.2-0.3	3877
0.3-0.4	316
0.4-0.5	65
0.5-0.6	75
0.6-0.7	31
0.7-0.8	0
0.8-0.85	1
0.85-0.9	1
0.9-0.95	1
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.9213	High Similarity	NPC146857
0.8542	High Similarity	NPC194716
0.8229	Intermediate Similarity	NPC329636
0.7766	Intermediate Similarity	NPC475556
0.7766	Intermediate Similarity	NPC311706
0.7579	Intermediate Similarity	NPC32793
0.7579	Intermediate Similarity	NPC116075
0.7449	Intermediate Similarity	NPC329986
0.7449	Intermediate Similarity	NPC140092
0.7396	Intermediate Similarity	NPC608063
0.7273	Intermediate Similarity	NPC247190
0.7184	Intermediate Similarity	NPC74259
0.7143	Intermediate Similarity	NPC475629
0.7071	Intermediate Similarity	NPC125077
0.7019	Intermediate Similarity	NPC120390
0.7	Intermediate Similarity	NPC469749
0.6809	Remote Similarity	NPC17896
0.6809	Remote Similarity	NPC469755
0.6809	Remote Similarity	NPC284406
0.6809	Remote Similarity	NPC197707
0.6809	Remote Similarity	NPC251866
0.6702	Remote Similarity	NPC84987
0.6698	Remote Similarity	NPC475419
0.6667	Remote Similarity	NPC180079
0.6606	Remote Similarity	NPC474423
0.6569	Remote Similarity	NPC59288
0.6505	Remote Similarity	NPC232785
0.6505	Remote Similarity	NPC486139
0.6355	Remote Similarity	NPC475590
0.6354	Remote Similarity	NPC219085
0.633	Remote Similarity	NPC117445
0.633	Remote Similarity	NPC308262
0.6273	Remote Similarity	NPC329784
0.625	Remote Similarity	NPC486143
0.625	Remote Similarity	NPC486135
0.625	Remote Similarity	NPC486142
0.625	Remote Similarity	NPC486137
0.625	Remote Similarity	NPC486149
0.6226	Remote Similarity	NPC486138
0.6226	Remote Similarity	NPC276838
0.6182	Remote Similarity	NPC474908
0.6122	Remote Similarity	NPC6108
0.6122	Remote Similarity	NPC89514
0.6061	Remote Similarity	NPC10823
0.6061	Remote Similarity	NPC480914
0.6058	Remote Similarity	NPC188234
0.6	Remote Similarity	NPC486127
0.5981	Remote Similarity	NPC486146
0.596	Remote Similarity	NPC157376
0.596	Remote Similarity	NPC142066
0.596	Remote Similarity	NPC603972
0.5943	Remote Similarity	NPC208193
0.5918	Remote Similarity	NPC99728
0.5918	Remote Similarity	NPC87250
0.5918	Remote Similarity	NPC244402
0.5918	Remote Similarity	NPC50305
0.5909	Remote Similarity	NPC486144
0.5909	Remote Similarity	NPC486145
0.5909	Remote Similarity	NPC486147
0.5909	Remote Similarity	NPC486136
0.5909	Remote Similarity	NPC486148
0.5905	Remote Similarity	NPC486130
0.5849	Remote Similarity	NPC264336
0.5841	Remote Similarity	NPC486150
0.5816	Remote Similarity	NPC474418
0.581	Remote Similarity	NPC236973
0.581	Remote Similarity	NPC32177
0.581	Remote Similarity	NPC469756
0.581	Remote Similarity	NPC275901
0.58	Remote Similarity	NPC5311
0.58	Remote Similarity	NPC77299
0.58	Remote Similarity	NPC34390
0.58	Remote Similarity	NPC480906
0.5784	Remote Similarity	NPC9499
0.5784	Remote Similarity	NPC471360
0.5784	Remote Similarity	NPC469751
0.5784	Remote Similarity	NPC471361
0.5784	Remote Similarity	NPC86159
0.5784	Remote Similarity	NPC469752
0.5784	Remote Similarity	NPC469754
0.5784	Remote Similarity	NPC70542
0.5676	Remote Similarity	NPC486128
0.5673	Remote Similarity	NPC72260
0.5614	Remote Similarity	NPC486134
0.5614	Remote Similarity	NPC486141
0.5588	Remote Similarity	NPC243196
0.5586	Remote Similarity	NPC475219
0.5586	Remote Similarity	NPC486132
0.5586	Remote Similarity	NPC486131
0.5524	Remote Similarity	NPC480907
0.5505	Remote Similarity	NPC55532
0.55	Remote Similarity	NPC158344
0.5478	Remote Similarity	NPC486140
0.5463	Remote Similarity	NPC480910
0.5463	Remote Similarity	NPC240070
0.5463	Remote Similarity	NPC480909
0.5421	Remote Similarity	NPC30483
0.5421	Remote Similarity	NPC470897
0.5413	Remote Similarity	NPC610296
0.5385	Remote Similarity	NPC146456
0.537	Remote Similarity	NPC292467
0.534	Remote Similarity	NPC469750
0.5299	Remote Similarity	NPC486133
0.5288	Remote Similarity	NPC76572
0.5288	Remote Similarity	NPC193382
0.5273	Remote Similarity	NPC231518
0.5273	Remote Similarity	NPC488944
0.5243	Remote Similarity	NPC309034
0.5243	Remote Similarity	NPC484211
0.5238	Remote Similarity	NPC77319
0.5238	Remote Similarity	NPC484212
0.5238	Remote Similarity	NPC471351
0.5238	Remote Similarity	NPC471355
0.5207	Remote Similarity	NPC486152
0.5189	Remote Similarity	NPC471359
0.5189	Remote Similarity	NPC483822
0.5146	Remote Similarity	NPC99620
0.514	Remote Similarity	NPC469753
0.514	Remote Similarity	NPC471354
0.514	Remote Similarity	NPC27507
0.513	Remote Similarity	NPC488943
0.513	Remote Similarity	NPC488942

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

● The left chart: Distribution of similarity level between NPC329675 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6500
0.1-0.2	2563
0.2-0.3	71
0.3-0.4	3
0.4-0.5	8
0.5-0.6	4
0.6-0.7	1
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.6809	Remote Similarity	NPD7319	Approved
0.5673	Remote Similarity	NPD8294	Phase 4
0.5505	Remote Similarity	NPD8377	Phase 4
0.5273	Remote Similarity	NPD8033	Approved
0.5094	Remote Similarity	NPD8335	Phase 4

Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity

B: biological targets similarity

C: networks similarity

D: cell-based bioactivity similarity

E: similarity based on clinical data