NPASS Compound

Natural Product: NPC329636

Natural Product ID	NPC329636
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Madagascarensilide C
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)-5-[(2S,4R,5S,6R)-5-hydroxy-4-methoxy-6-methyloxan-2-yl]oxy-4-methoxy-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 C
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1644521
PubChem CID	53323542
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 124131 0 0 0 0 0 0 0 0999 V2000 -11.3934 0.8983 -2.1181 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.6087 1.8055 -1.2105 C 0 0 0 0 0 0 0 0 0 0 0 0 -11.2895 1.9798 0.1383 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.1873 1.9465 1.1934 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.6301 0.5182 1.1431 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.1396 0.2888 -0.2648 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.2932 1.4245 -1.0673 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.7776 0.0378 -0.1941 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.4681 -1.2255 -0.7315 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6420 -0.9329 -1.9899 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3725 -0.5036 -1.6680 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.6353 -1.4358 -0.9642 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4408 -2.5360 -0.3596 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6812 -1.9774 0.2899 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.4434 -2.9597 0.9039 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.5075 -2.8065 2.2896 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9828 -0.7529 0.0779 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6049 -0.8138 -0.0431 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0893 0.5884 -0.2486 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7756 0.7317 0.1834 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0298 -0.4250 0.0273 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4722 -1.5458 0.9223 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9689 -1.4681 1.1644 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2814 -0.7604 2.3001 O 0 0 0 0 0 0 0 0 0 0 0 0 1.3127 -0.1515 0.1591 O 0 0 0 0 0 0 0 0 0 0 0 0 2.0285 -0.3490 -1.0023 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6274 0.9046 -1.5542 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0203 1.2032 -1.1356 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9196 -0.0205 -1.0352 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2432 0.4327 -0.5277 C 0 0 0 0 0 0 0 0 0 0 0 0 7.2652 0.4581 -1.6381 C 0 0 0 0 0 0 0 0 0 0 0 0 8.6230 0.9578 -1.1639 C 0 0 0 0 0 0 0 0 0 0 0 0 9.0896 0.1031 -0.0508 C 0 0 0 0 0 0 0 0 0 0 0 0 10.3111 0.5070 0.6889 C 0 0 0 0 0 0 0 0 0 0 0 0 10.0575 0.1823 2.1779 C 0 0 0 0 0 0 0 0 0 0 0 0 8.7389 -0.5775 2.1683 C 0 0 0 0 0 0 0 0 0 0 0 0 8.0449 0.1073 1.0352 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7179 -0.3933 0.6678 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5371 -1.8184 0.3446 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0281 -2.1112 0.3745 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2015 -0.9730 -0.0940 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0037 -1.4897 -0.8640 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6874 -0.2512 0.9991 O 0 0 0 0 0 0 0 0 0 0 0 0 7.8826 1.4376 1.4276 O 0 0 0 0 0 0 0 0 0 0 0 0 10.8386 1.8607 0.5204 C 0 0 0 0 0 0 0 0 0 0 0 0 12.0134 2.0804 -0.1021 C 0 0 0 0 0 0 0 0 0 0 0 0 12.3210 3.4965 -0.1426 C 0 0 0 0 0 0 0 0 0 0 0 0 13.3300 4.0548 -0.6449 O 0 0 0 0 0 0 0 0 0 0 0 0 11.2795 4.1213 0.4845 O 0 0 0 0 0 0 0 0 0 0 0 0 10.3622 3.1711 0.9517 C 0 0 0 0 0 0 0 0 0 0 0 0 9.3486 -1.3104 -0.5707 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0020 -0.5951 -2.4174 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4298 -0.1068 -3.3771 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.0014 1.6239 0.3734 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6837 -2.0595 -2.9722 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.6612 2.2801 2.4409 O 0 0 0 0 0 0 0 0 0 0 0 0 -9.9059 3.3526 2.9135 C 0 0 0 0 0 0 0 0 0 0 0 0 -12.1336 0.8735 0.3179 O 0 0 0 0 0 0 0 0 0 0 0 0 -11.8915 0.0752 -1.5885 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.6902 0.4576 -2.8561 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.1338 1.5170 -2.6847 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.5940 2.8210 -1.6854 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.8694 2.9013 0.2016 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.3333 2.5930 0.8599 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.8749 0.3453 1.9119 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.4813 -0.1851 1.3493 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.6201 -0.5929 -0.7331 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.3725 -1.7485 -1.0933 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1588 -0.0558 -2.4723 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8760 -1.8724 -1.6495 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6427 -3.3851 -1.0282 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8220 -2.9632 0.4838 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3151 -1.3063 1.1199 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.1349 -3.6370 2.6716 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5255 -2.8706 2.7721 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.0590 -1.8663 2.5386 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3915 -1.4039 -0.9615 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0918 0.7838 -1.3404 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2066 -0.7526 -1.0297 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2977 -2.5007 0.3849 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0991 -1.6092 1.8628 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3780 -2.4874 1.2529 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4833 -1.3917 3.0396 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2843 -0.6975 -1.7799 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4914 0.9842 -2.6729 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9860 1.7514 -1.1661 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9782 1.6466 -0.1026 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4375 1.9742 -1.7903 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2023 1.4914 -0.1343 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8925 1.2596 -2.3455 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2984 -0.4497 -2.2327 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4967 2.0064 -0.9290 H 0 0 0 0 0 0 0 0 0 0 0 0 9.3043 0.7954 -2.0401 H 0 0 0 0 0 0 0 0 0 0 0 0 11.1581 -0.2374 0.4515 H 0 0 0 0 0 0 0 0 0 0 0 0 9.8826 1.1132 2.7524 H 0 0 0 0 0 0 0 0 0 0 0 0 10.8780 -0.3489 2.6479 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1539 -0.3477 3.0946 H 0 0 0 0 0 0 0 0 0 0 0 0 8.8519 -1.6557 2.0900 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0118 -0.1266 1.4889 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8459 -2.1242 -0.6806 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9572 -2.4940 1.1357 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7207 -2.4032 1.4073 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8018 -2.9975 -0.2649 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5210 -2.2994 -0.3031 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2928 -1.8044 -1.9013 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2593 -0.9392 1.5926 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9236 1.5619 2.3979 H 0 0 0 0 0 0 0 0 0 0 0 0 12.6737 1.3246 -0.5328 H 0 0 0 0 0 0 0 0 0 0 0 0 10.3664 3.2799 2.0705 H 0 0 0 0 0 0 0 0 0 0 0 0 9.3751 3.4922 0.5462 H 0 0 0 0 0 0 0 0 0 0 0 0 9.0933 -2.0976 0.1296 H 0 0 0 0 0 0 0 0 0 0 0 0 10.4655 -1.4080 -0.7335 H 0 0 0 0 0 0 0 0 0 0 0 0 8.9412 -1.4070 -1.5949 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5905 -1.4927 -2.6218 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7523 1.1747 1.0593 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4209 2.4488 0.8625 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6176 2.1568 -0.4093 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1319 -1.7464 -3.9608 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6743 -2.4542 -3.2391 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3663 -2.8886 -2.6220 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.0518 4.1872 2.1744 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.2369 3.6532 3.9134 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.8561 3.0622 2.9250 H 0 0 0 0 0 0 0 0 0 0 0 0 -13.0476 1.1134 -0.0214 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 12 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 21 25 1 0 25 26 1 0 26 27 1 0 27 28 1 0 28 29 1 0 29 30 1 0 30 31 1 0 31 32 1 0 32 33 1 0 33 34 1 0 34 35 1 0 35 36 1 0 36 37 1 0 37 38 1 0 38 39 1 0 39 40 1 0 40 41 1 0 41 42 1 0 41 43 1 0 37 44 1 0 34 45 1 0 45 46 2 0 46 47 1 0 47 48 2 0 47 49 1 0 49 50 1 0 33 51 1 0 29 52 1 0 52 53 2 0 19 54 1 0 10 55 1 0 4 56 1 0 56 57 1 0 3 58 1 0 7 2 1 0 14 9 1 0 23 18 1 0 42 26 1 0 41 29 1 0 38 30 1 0 37 33 1 0 50 45 1 0 1 59 1 0 1 60 1 0 1 61 1 0 2 62 1 0 3 63 1 0 4 64 1 0 5 65 1 0 5 66 1 0 6 67 1 0 9 68 1 0 10 69 1 0 12 70 1 0 13 71 1 0 13 72 1 0 14 73 1 0 16 74 1 0 16 75 1 0 16 76 1 0 18 77 1 0 19 78 1 0 21 79 1 0 22 80 1 0 22 81 1 0 23 82 1 0 24 83 1 0 26 84 1 0 27 85 1 0 27 86 1 0 28 87 1 0 28 88 1 0 30 89 1 0 31 90 1 0 31 91 1 0 32 92 1 0 32 93 1 0 34 94 1 0 35 95 1 0 35 96 1 0 36 97 1 0 36 98 1 0 38 99 1 0 39100 1 0 39101 1 0 40102 1 0 40103 1 0 42104 1 0 42105 1 0 43106 1 0 44107 1 0 46108 1 0 50109 1 0 50110 1 0 51111 1 0 51112 1 0 51113 1 0 52114 1 0 54115 1 0 54116 1 0 54117 1 0 55118 1 0 55119 1 0 55120 1 0 57121 1 0 57122 1 0 57123 1 0 58124 1 0 M END

Standard InCHIKey	OKKMMWPTBZXHLN-QTRLOGHOSA-N
Standard InCHI	InChI=1S/C43H66O15/c1-22-37(47)31(50-5)17-35(53-22)58-39-24(3)55-36(18-32(39)51-6)57-38-23(2)54-34(16-30(38)45)56-26-7-12-41(21-44)28-8-11-40(4)27(25-15-33(46)52-20-25)10-14-43(40,49)29(28)9-13-42(41,48)19-26/h15,21-24,26-32,34-39,45,47-49H,7-14,16-20H2,1-6H3/t22-,23-,24-,26+,27-,28+,29-,30+,31-,32+,34+,35+,36+,37+,38-,39-,40-,41+,42+,43+/m1/s1
SMILES	CC1C(C(CC(O1)OC2C(OC(CC2OC)OC3C(OC(CC3O)OC4CCC5(C6CCC7(C(CCC7(C6CCC5(C4)O)O)C8=CC(=O)OC8)C)C=O)C)C)OC)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	822.44	Volume:	807.776 ? Van der Waals volume.
Dense:	1.018	LogP:	1.809 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.254 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.274 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	10.0	Rigid Bonds:	45.0
TPSA:	198.13 ? Topological Polar Surface Area.	H-Bond Acceptor:	15.0
H-Bond Donor:	4.0	Rings:	8.0
Heavy Atoms:	15.0

MedChem Properties

QED Drug-Likeness Score:	0.143	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	6.244	Fsp³:	0.907
MCE-18:	151.463 ? 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:	0.003	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:	0.174 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.353	Promiscuous compounds:	0.004

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.53	MDCK Permeability:	-5.106
Pgp-inhibitor:	0.0	Pgp-substrate:	0.989
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):	0.934
20% Bioavailability (F20%):	0.126	30% Bioavailability (F30%):	0.353
50% Bioavailability (F50%):	0.956

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.006	MRP1:	0.996
Plasma Protein Binding (PPB):	59.746%	Volume Distribution (VD):	-0.052
Fu:	38.889% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.0
OATP1B3 inhibitor:	0.546	BCRP inhibitor:	0.0
BSEP inhibitor:	0.476

ADMET: Metabolism

CYP1A2-inhibitor:	0.003	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.923	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.014	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.96	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.993	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):

2.933

Half-life (T1/2):

6.839

ADMET: Toxicity

hERG Blockers:	0.512	hERG Blockers (10um):	0.556
Human Hepatotoxicity (H-HT):	0.843	Drug-induced Liver Injury (DILI):	0.418
AMES Toxicity:	0.964	Rat Oral Acute Toxicity:	0.987
Maximum Recommended Daily Dose:	0.998	Skin Sensitization:	0.672
Carcinogencity:	0.492	Eye Corrosion:	0.0
Eye Irritation:	0.0	Respiratory Toxicity:	0.623
Drug-induced Neurotoxicity:	0.267	Ototoxicity:	0.993
Hematotoxicity:	0.096	Drug-induced Nephrotoxicity:	0.194
Genotoxicity:	0.999	RPMI-8226 Immunitoxicity:	0.755
A549 Cytotoxicity:	0.318	Hek293 Cytotoxicity:	0.976
BCF:	0.525 ? 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:	3.645 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.641 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.488 ? 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	=	170.0	nM	PMID[12828470]
NPT397	Cell line	NCI-H460	Homo sapiens	IC50	=	370.0	nM	PubChem BioAssay data set

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 NPC329636 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	16946
0.1-0.2	30740
0.2-0.3	1831
0.3-0.4	147
0.4-0.5	112
0.5-0.6	51
0.6-0.7	26
0.7-0.8	0
0.8-0.85	2
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8256	Intermediate Similarity	NPC180079
0.8229	Intermediate Similarity	NPC329675
0.75	Intermediate Similarity	NPC146857
0.7222	Intermediate Similarity	NPC34390
0.7083	Intermediate Similarity	NPC608063
0.699	Remote Similarity	NPC194716
0.6848	Remote Similarity	NPC6108
0.6848	Remote Similarity	NPC89514
0.6526	Remote Similarity	NPC484212
0.6316	Remote Similarity	NPC17896
0.6316	Remote Similarity	NPC469755
0.6316	Remote Similarity	NPC284406
0.6316	Remote Similarity	NPC197707
0.6316	Remote Similarity	NPC251866
0.625	Remote Similarity	NPC84949
0.625	Remote Similarity	NPC480562
0.625	Remote Similarity	NPC74945
0.625	Remote Similarity	NPC10823
0.625	Remote Similarity	NPC31354
0.625	Remote Similarity	NPC69576
0.6238	Remote Similarity	NPC475556
0.6238	Remote Similarity	NPC311706
0.6122	Remote Similarity	NPC483822
0.6117	Remote Similarity	NPC55532
0.6078	Remote Similarity	NPC32793
0.6078	Remote Similarity	NPC116075
0.6058	Remote Similarity	NPC469749
0.6042	Remote Similarity	NPC219085
0.6	Remote Similarity	NPC329986
0.6	Remote Similarity	NPC140092
0.6	Remote Similarity	NPC474418
0.5849	Remote Similarity	NPC247190
0.5842	Remote Similarity	NPC72260
0.5818	Remote Similarity	NPC74259
0.5714	Remote Similarity	NPC475629
0.5676	Remote Similarity	NPC120390
0.566	Remote Similarity	NPC125077
0.5455	Remote Similarity	NPC99728
0.5455	Remote Similarity	NPC87250
0.5455	Remote Similarity	NPC244402
0.5455	Remote Similarity	NPC50305
0.54	Remote Similarity	NPC484211
0.5398	Remote Similarity	NPC475419
0.5392	Remote Similarity	NPC250556
0.5347	Remote Similarity	NPC157376
0.5347	Remote Similarity	NPC142066
0.5347	Remote Similarity	NPC603972
0.5345	Remote Similarity	NPC474423
0.534	Remote Similarity	NPC9499
0.534	Remote Similarity	NPC471360
0.534	Remote Similarity	NPC469751
0.534	Remote Similarity	NPC93883
0.534	Remote Similarity	NPC471361
0.534	Remote Similarity	NPC86159
0.534	Remote Similarity	NPC469752
0.534	Remote Similarity	NPC469754
0.534	Remote Similarity	NPC70542
0.5288	Remote Similarity	NPC469753
0.5248	Remote Similarity	NPC84987
0.5229	Remote Similarity	NPC59288
0.52	Remote Similarity	NPC158344
0.5196	Remote Similarity	NPC99080
0.5192	Remote Similarity	NPC471359
0.5192	Remote Similarity	NPC484202
0.5182	Remote Similarity	NPC232785
0.5182	Remote Similarity	NPC486139
0.5161	Remote Similarity	NPC72772
0.5149	Remote Similarity	NPC471633
0.5146	Remote Similarity	NPC199428
0.5146	Remote Similarity	NPC109448
0.5146	Remote Similarity	NPC152615
0.5146	Remote Similarity	NPC310341
0.5088	Remote Similarity	NPC475590
0.5086	Remote Similarity	NPC117445
0.5086	Remote Similarity	NPC308262
0.5048	Remote Similarity	NPC305574
0.5047	Remote Similarity	NPC103534
0.5047	Remote Similarity	NPC44899
0.5047	Remote Similarity	NPC173555
0.5047	Remote Similarity	NPC304260
0.5047	Remote Similarity	NPC29639
0.5043	Remote Similarity	NPC329784

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC329636 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6465
0.1-0.2	2628
0.2-0.3	39
0.3-0.4	5
0.4-0.5	4
0.5-0.6	7
0.6-0.7	2
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
0.66	Remote Similarity	NPD8377	Phase 4
0.6316	Remote Similarity	NPD7319	Approved
0.596	Remote Similarity	NPD7516	Pre-clinical
0.5842	Remote Similarity	NPD8294	Phase 4
0.5755	Remote Similarity	NPD8378	Pre-clinical
0.5755	Remote Similarity	NPD8379	Approved
0.5392	Remote Similarity	NPD7507	Pre-clinical
0.5243	Remote Similarity	NPD8335	Phase 4
0.5047	Remote Similarity	NPD8296	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